Ep 142: Doctors by Nature (with Jaap de Roode)

Ep 142: Doctors by Nature (with Jaap de Roode)

Big Biology

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How do animals use medication and can humans learn from them? What are the evolutionary consequences of animal self-medication?

In this episode, we talk with Jaap de Roode, Professor of Biology at Emory University and author of the book Doctors by Nature: How Ants, Apes, and Other Animals Heal Themselves. Jaap’s research on monarch butterflies using toxic milkweed as a deterrent against parasites sparked his interest in the larger topic of how often often animals use medication. We talk with Jaap about why and how animals self-medicate, what kinds of things we’ve learned about their behavior that could inform our use of medicine, and how such complex behavior evolved in sometimes simple organisms. what kinds of things we’ve learned about their behavior that could inform our use of medicine, and how such complex behavior evolved in sometimes simple organisms.

Cover art by Brianna Longo

• Episode Transcript

  Marty Martin  0:05  

  Have you ever watched an animal do something that made you think, wait a second, that looks like medicine?

  John Drake  0:11  

  I have. And one of my favorite examples comes from Jane Goodall's early work in Gombe. She noticed chimpanzees swallowing whole leaves of a plant called Aspilia pluriseta. They didn't chew them. They folded them up like little parcels and just gulped them down.

  Marty Martin  0:24  

  Oh, right. And when she and her colleagues checked later, those same leaves turned up in the dung, but they were intact and wrapped around expelled worms. I think it was the first solid evidence that wild animals deliberately treat themselves for infection.

  John Drake  0:36  

  Yep, that observation changed the way biologists think about animal behavior. It hinted that animals can sense illness, find a remedy, and use it, not randomly, but with a purpose. And it set the stage for a whole new field called zoopharmacognosy, literally, animal drug knowing. I wonder if I even said that right.

  Marty Martin  0:55  

  Hold on a minute. John Drake, what are you doing here? I was expecting Cam.

  John Drake  0:59  

  I get that a lot. Well, actually, not really. It'd be pretty hard to mistake me for the great Cam Ghalambor, but Cam and the team invited me to join as a guest co-host for a few episodes this season. So for today, at least you're stuck with me.

  Marty Martin  1:11  

  All right, then listeners meet John Drake, Regent's Professor of ecology and infectious disease modeling at the University of Georgia, and if I may say, a long time friend of Big Biology.

  John Drake  1:20  

  Thanks, Marty. I've been a fan since episode one, and I'm thrilled to sit in for a few conversations. The intersection of evolution, ecology and behavior is home territory for me, and today's episode fits right in that sweet spot.

  Marty Martin  1:32  

  Okay, then back to zoopharmacognosy. It's a field that's small but growing fast, and one of its leading voices is our guest today, Jaap de Roode, a professor of Biology at Emory University, many listeners will know Jaap from his beautiful work on monarch butterflies and their parasites.

  John Drake  1:48  

  Jaap showed that infected caterpillars prefer milkweed species that are rich in toxic cardinaloids. Those toxins kill the parasite more than they harm the host, which means the caterpillars are effectively medicating themselves. It was the first clear experimental proof that self medication could evolve through natural selection.

  Marty Martin  2:04  

  Jaap's new book Doctors by Nature tells that story and dozens more. Bears gnawing at willow bark, nature's original aspirin, wooly bears eating toxic plants to fend off parasitoid flies, sparrows weaving cigarette butts through their nests to repel mites and even honey bees collecting tree resins to sterilize their hives. It's a natural history of medicine that spans the tree of life.

  John Drake  2:24  

  What I like about Jaap's book is that he doesn't treat these behaviors as curiosities. He asks what makes something medicine in some biological sense, laying out four forms of medication, prophylaxis, therapy, body anointing and fumigation, and then he applies strict criteria to animal behaviors to qualify them as medicating, the behavior must improve health or fitness, involve an external substance, be actively chosen and carry a cost when infection isn't present.

  Marty Martin  2:52  

  And that last cost part is crucial. In nature, even the right remedy can hurt you if you take it when you don't need it. A caterpillar that eats toxic milk, weed pays a price in slower growth, a chimp that swallows rough leaves risks harming its gut. And these costs are the best evidence that animals are aware of what they're doing. That is, the behavior is adaptive, because they do it only when they're ill, not randomly

  John Drake  3:15  

  Medicine, in Jaap's telling,  therefore isn't a human invention, but rather an evolved strategy. Selection favors individuals that balance the benefits of treatment against the cost of toxicity or energy loss. The result looks like foresight, and maybe sometimes it is, but it's also the product of generations of trial and error.

  Marty Martin  3:32  

  We'll talk with you Jaap about how animals discover these medicines, what sensory cues they used, taste, smell, feedback from their own physiology, and whether self medication can influence the evolution of the parasites themselves. If a host can limit infection, maybe that pushes parasites towards slower virulence.

  John Drake  3:48  

  We'll also explore how humans might learn from nature's doctors. Farmers who let sheep choose among plants, often see better parasite control. Beekeepers now use propolis strategically to reduce disease in hives. There's a lot of practical knowledge hiding in these behaviors.

  Marty Martin  4:02  

  And of course, we'll ask about the limits. Do animals ever make mistakes? Can they overdose, develop dependencies or misread cues as humans? We certainly do. So. What keeps the rest of the animal kingdom from the same trap

  John Drake  4:14  

  Beyond the science, Jaap's  book is also a story about humility. We like to think medicine started with us, with shamans, pharmacists, white coated doctors, but the impulse to heal is older and deeper. The forest and the savannah have been running clinical trials, so to speak, for millions of years.

  Marty Martin  4:28  

  There's something profoundly hopeful about that. It means that health is woven into the fabric of life. For monarchs, chimpanzees, bees and people, all of us are trying to stay well in a world full of pathogens. That continuity makes biology feel personal.

  John Drake  4:43  

  It also brings wonder back to the everyday. The next time your dog eats grass or your cat rolls in catnip, maybe it's not just quirky behavior, it might be evolution's quiet wisdom at work.

  Marty Martin  4:53  

  So in today's episode, we dive into Jaap's research, his book, and the broader implications for ecology, evolution and human medicine. We learn how animals self prescribe, what the cost of benefits look like, and how this knowledge can help us care for our own species a little better.

  John Drake  5:06  

   But before we start, we're still in fundraising mode. Our goal is 500 paid sub stack subscribers, and we're closing in

  Marty Martin  5:12  

  for every 20 new paid subscribers, we randomly select one listener to receive a big biology t-shirt or an episode art print, and when we hit that lucky number 500 the supporter gets a sweatshirt and a large frame to print.

  John Drake  5:24  

  Head to big biology dot substack dot com, sign up and help us keep bringing you big ideas from across the life sciences. Paid subscribers also get full length episodes behind the scenes, debriefs and extra audio from our guests. 

  Marty Martin  5:37  

  I'm Marty Martin 

  John Drake  5:38  

  And I'm John Drake, and you're listening to big biology.

  Marty Martin  5:53  

  So Jaap de Roode, Welcome to Big Biology!

  Jaap de Roode  5:55  

  Thanks so much for having me. Pleasure to be here. 

  Marty Martin  5:57  

  Excellent. We're really excited to have you here to talk about your new book, Doctors by Nature. I really enjoyed reading it, and I highly recommend it that listeners pick up a copy. But to start tell us why you wrote this book. You've worked on lots of things, and could have written lots of different books on different topics. So why this particular one? 

  Jaap de Roode  6:04  

  I  think it's just so amazing to tell people about the ways that animals can use medicine. We often think that humans are kind of special, and we're always looking for ways that we are different, and that's especially so in Western culture. But it turns out that animals are really good at using all sorts of medicines, and all sorts of animals can do that. And I think that story is just so amazing, not just for the fascination of it and showing how cool nature is, but also to show us what we can learn from animals to improve the health of them, but also us, and to actually find new medicines that they may discover for us.

  Marty Martin  6:50  

  Yeah, okay, and I think we're obviously going to spend a lot of time on all of those various, various different species and the things that they do, but one of the species that you really focus on in the book are the monarch butterflies. You could have written an entire book just on migrations and you know, their beauty and the behaviors and such, but there is something special to you about them. And maybe, I mean, I'm giving away some of the thunder from the book, so I'll let you tell this story. But what is it about the monarchs that played a role in this particular topic?

  Jaap de Roode  7:19  

  Yeah, and that is how I got into the topic in the first place, because monarch butterflies become sick. They become sick with parasites, and you already alluded to them being pretty and doing the spectacular migration, and that's how most people know about monarch butterflies, right? Especially when you live in North America, monarchs from Canada, the United States migrate to Mexico every year, where tens of millions of monarchs come together. It's really, really beautiful, spectacular. They're also very pretty, very clear, big orange butterflies. But I always like to tell people, that's not the reasons I study them. I study them because they become sick. And we're very well aware, of course, that humans become sick with pathogens, parasites, all sorts of infectious diseases. We know this about our pets. Some people don't realize that all wild animals get infections as well, and so it is for monarch butterflies. So I started studying them to figure out what do they become sick with? What do they do about it? And then ultimately discovered that they can use medicine.

  Marty Martin  8:17  

  You must have gotten pushback early to ask the crazy question that butterflies get sick, I mean, and then the medication in general, I mean, that's, I would imagine, kind of a taboo thing to even ask.

  Jaap de Roode  8:31  

  Yeah, no, you're absolutely right. And so, so to give a little bit of a background of what we actually found- when I first came to the United States in 2005 to study monarch butterflies, I really came to study their parasites, and I very quickly learned that monarch butterflies are specialist feeders, as caterpillars, on milkweeds. So adult butterflies can drink nectar from any flower, but the caterpillars can only eat milkweed. So you give them lettuce or you give them an oak leaf, they cannot eat it. They'll die. And these milkweeds contain chemicals that are called cardenolides. They're also known as hard poisons, very toxic chemicals. And traditionally, biologists have really looked at that as the monarchs using those toxins, taking them out of the milkweeds, and using them as protection against predators. But because I was so biased thinking about parasites, I wanted to see if they can also use them against parasites. 

  Jaap de Roode  9:24  

  And so we started with very simple experiments rearing monarch butterflies on more and less toxic milkweed, and found that the more toxic milkweed really reduced the infection probability of the caterpillars, but also when they became infected, they suffered less from parasite growth and had fewer disease symptoms. And so having found that, then it was the question, Can caterpillars use this, or can the adults actually use it? So the question is, we know the plants can work medicinally. Can the animals actively use them as medicine? And you're right, that was kind of controversial. Because I remember when we wrote up the paper to report on the fact that some milkweeds act medicinally and others do not, and speculated in the discussion that we should then figure out if monarchs can use it. One of the reviewers said there's absolutely no way, and the editor made us remove it from the discussion. And that was frustrating, but nothing like good frustration to spur you on to do the research, right? 

  Jaap de Roode  10:25  

  And so then we did the research following that, and we did two types of experiments. One was with caterpillars. So we had sick caterpillars and healthy caterpillars. Gave them choices between the medicinal, non-medicinal milkweed, absolutely no result, no effect. The caterpillars just ate whatever they found first. But then we really thought that kind of makes sense, because the caterpillars don't decide what they eat. It's their mothers that decide what they eat. It's the mothers that lay the eggs on the food, on the plant. The caterpillars come out, they're born on their food, that's what they're gonna eat. So then we did our other series of experiments with the adult butterflies, specifically looking at mothers that were sick, mothers that were not sick, where do they lay their eggs? And found that they prefer to lay the eggs, when you give them a choice, on the more medicinal milkweed, and that then protects her offspring, not herself. But what happens is she actually passes on the parasites to the eggs, and when the caterpillars come out of the eggs, they get the parasites, but at the same time, they get this medicine that then reduces their infection and their disease.

  John Drake  11:30  

  Yeah, so it kind of sounds to me, Jaap, like the distinction you're drawing between chemicals or toxins and medicines has something to do with whether or not the one taking them does that intentionally? I'm wondering if you have a fair and broad definition of medicine as a concept, something that could apply both to people and to animals?

  Jaap de Roode  11:49  

  It's a great question, and the answer is no, and it's actually the funny thing is, when I was writing the book, I actually had a whole chapter on trying to define what medicine is, and my editor decided, and I agreed that chapter wasn't going anywhere. 

  John Drake  12:04  

  Oh, I would have liked that chapter. 

  Marty Martin  12:05  

  I would like see that too.

  Jaap de Roode  12:06  

  You would have liked it? Well, it was, it was very meandering, because, you know, even think about, how do we define medicine as humans, right? So that we have, you know, you and I probably have a very different view of medicine  than if I talk to a traditional Chinese healer, right? So you already start thinking about, so what is medicine? So I for writing the book, I was more focused on what is medication, and so I restricted myself. Made it a little bit easier for me. So I excluded everything, such as surgery, right? So I really focused on the use of chemicals, and those chemicals come not from the body itself, but animals or humans, get those chemicals from their environment, whether it's fungi, whether it's animals, whether it's plants, they get it from another source. And then the other thing that was really important is that, you know, there's a lot of chemicals, and oftentimes the chemicals, whether they have an effect, whether they act as food or medicine or poison, comes down to the dose. But it also means that the way we define it, a lot of people, when they study medication in animals, really define it as using a chemical that, at high enough doses are also going to have side effects. So that's something that animals and humans have in common. You know, when we take medicine, whether it is traditional medicine or we take medicine from our pharmacist, there's that whole leaflet with all the side effects, and you see that with animals as well. So I think that's an important thing that they have in common. 

  John Drake  13:32  

  So medicine is facultative then, right? So I think you're saying that it only counts as medicine if it harms you when you're well, but it is beneficial when you're sick?

  Jaap de Roode  13:42  

  Medication. So I, you know, I think medicine is a lot broader, so I restrict myself to medication. So the use of medicines, slash drugs. Yes, that you, you know, you use them, but there is side effects, and so when you don't need them, you avoid them. And we see that, of course, in humans, but we see that in animals as well. So oftentimes, when animals use medicines, they pick out particular plants or particular chemicals that actually have these side effects, and when they don't need them, you see them avoiding them.

  Marty Martin  14:13  

  Okay, so it's understandable. Yeah, I hadn't thought about the complexity of medicine when you include surgery and presumably other behaviors that would keep you in good health and maybe prevent you from ever needing it. I guess this does get very complicated.

  Jaap de Roode  14:26  

  Exactly. So, you know, think about Ayurvedic medicine. You know, that includes yoga. So then the question is, well, actually, my dogs do yoga because they do the downward dog, right? So we have trained them to, you know, one of my puppies, he can do, when I say yoga with a treat, he'll do the downward dog. But, you know, which is also an aspect of health, right, stretching and keeping everything supple. And so it becomes very complicated, so I restricted myself to medication, yeah.

  Marty Martin  14:58  

  Okay, that makes sense. And then. You know? So it does. It's not the case. The book definitely doesn't dodge definitions. I mean, what I really liked about the book is that you are trying to be explicit about what behaviors you're attributing to these animals. So there are four different variants of medication that you spend some time on: prophylaxis, therapeutic medication, body anointing and fumigation. So they're all big classes, and I know there are lots of different stories, so maybe briefly explain a few of those and then give your favorite example.

  Jaap de Roode  15:29  

  Yeah, so I think it's nice to have that categorization, because they're all things that humans do as well. So when we think about therapeutic medication, that's the kind of medication you use when you are already sick, and so you do something in response to your symptoms. So you feel sick, and you go to the doctor, you get a medication and take that, and it takes care of your symptoms. So chimpanzees, for example, do this when they're infected with worms. They specifically suck the bitter pith of a plant called bitter leaf, and that then gets rid of those worms. 

  Jaap de Roode  16:02  

  The second category is prophylaxis, and this will be the kind of thing, you know, if I travel to an area where there is a lot of malaria, I take anti-malarials before I go. And so this is something that you do in anticipation of becoming infected, because the risk is so high, you start already taking the medicine before you get sick, because the risk of getting sick is so high. And but, you know, again, great, right? Because antimalarials, a lot of those have very strong side effects, so it's not something you want to keep on doing forever. So you do it when the risk is high. And so animals do this too. So there's particular baboons that live in areas where there's a lot of schistosome worm parasites, and they eat particular berries that are toxic to those parasites a lot more than the baboons that live in other places where there isn't as many of those. 

  Jaap de Roode  16:50  

  Then we have body anointing, and that's basically, you know, smearing stuff onto your skin or into your fur that keeps blood suckers away. And so we see that when we put anti-mosquito repellent on our skin to keep mosquitoes away, both to protect ourselves from the bites, but also from the parasites they transmit. I guess my favorite example is cats and the catnip response. So when cats roll around in catnip, or silver vine, which is a plant that occurs in Asia, it is much more potent than catnip. They coat themselves in chemicals that keep those mosquitoes away. And that's really cool, because humans have patented that chemical now to see if we can use it for us as well. 

  Jaap de Roode  17:30  

  And finally, like you mentioned, fumigation, and that's, you know. So some people may be familiar, especially if you live in areas with a lot of infectious diseases caused by mosquitoes. You may be aware of the trucks coming by and basically, you know, fogging your house just coming in with all these mosquito sprays.

  Marty Martin  17:47  

  Oh, living in Florida, I'm quite familiar with this phenomenon.

  Jaap de Roode  17:50  

  Exactly. And animals do that, and they're my favorite example is of house finches and sparrows that live in Mexico City and actually take discarded cigarette butts, put it in our nest, and that repels all sorts of ectoparasites such as mites and lice and ticks.

  John Drake  18:17  

  So Jaap, let's talk a little bit about the science of understanding self medication by animals. For a biologist to conclude that an animal is medicating, you have some conditions that you think are must be demonstrated. The behavior has to improve health or fitness. The resource used as a medicine has to be external. The animal has to seek out the resource, and that has to be costly in the absence of infection, setting aside the last one, because that's maybe the hardest one to get around. I wonder if you can explain why these are important. 

  Jaap de Roode  18:48  

  Yes, so the you know, and we're sure we're going to have a really fun discussion, but you really made me think about one of those conditions and but I'll start with that one, the condition that it has to help. Now, I think it's really important when you look at wild animals, and really this field started with observations, right? And it's really hard when you observe an animal, say a chimpanzee, is eating a particular plant, then it gets better. Do you really know that that is what happened, right? Is it the plant that did that? But when we talk about medication, we talk about a behavior. And so when we think about therapeutic medication, we think about an animal behaving differently when it is sick. Now, there are actually so many examples out there where it's not that changing behavior is not benefiting the animal, but the parasites. There are so many parasites and pathogens that are really good at manipulating the host to create behaviors that are good for the parasites. And you know, so really fantastic example is you think of rabies virus, for example, when that virus infects you, gets to your brain, causes this aggression, causes a lot of salivation, where a lot of the virus particles are. So animals, including humans, become aggressive and they bite others, they transmit that virus. It's a change in behaviors, it's absolutely not medication. That's the parasite doing the talking. So that's why we said, you know, you look at that behavior, it has to really help the host, not the parasite. So that is an important one.

  Jaap de Roode  20:13  

   It has to be intentional. And I think that that's one of the tricky parts. You know, there's a lot of kind of skepticism, especially early on in the 1980s but still, a lot of people say: "Well, you know, these animals, it's just accidental. They eat something and then, you know, it helps, but they didn't do it on purpose." So I think that intentionality is really important, because it shows the animal is really seeking out something when it is sick, or to prevent that sickness in the first place. 

  Jaap de Roode  20:42  

  And then the other thing is that it's a chemical or substance that is not made by the body. So, you know, you think about, we have a fantastic immune system, right? That takes care of a lot of infections. But I'm not going to call immune cells a medicine. So when we talk about the use of medicine, it's something they get from the environment, a chemical produced by a plant, or, you know, even the morphology, the little hairs on a leaf that can scrape out parasites, out of the gut, that kind of thing, so they don't make it themselves.

  Marty Martin  21:09  

  So I think that, I mean, it seems like the trickiness historically has been about the motivation and the attribution of this sophisticated way of thinking and planning and deliberating. So you use the words, it's a classic use of words in the book, but I'd like to hear more about what you mean when you say some behaviors are learned and some behaviors are innate. And it seemed over and over again, you're sort of invoking these are innate behaviors. What do you mean? I mean, I think that's how a lot of people would see it, but it almost felt like in saying that, well, now, okay, makes sense. To me, I'm not,   I don't, I don't necessarily feel any better about something being an innate than learned. And feels like psychology has changed a little bit where innate is no longer the simplified way of thinking about things as maybe it was pitched in the time of Piaget and others that popularized those ideas.

  Jaap de Roode  21:59  

  Yeah. It's also interesting, right? Because innate is essentially the new word for instinct, because instinct has kind of gone out of vogue in the behavioral field. But first of all, what I like to say, you know, when I talk about intentionality, a lot of people misinterpret that as animals knowing exactly what they do and having this complete awareness of what they are doing. And I think in most cases, animals don't know that they're infected. They don't know that what they're using is a medicine. They don't know that that kills parasites and that therefore they get better. I think the intentionality can still be there as a response to a different state of the body. And so my favorite example comes from wooly bear caterpillars and so beautiful research. These caterpillars get infected by parasitoid flies. Now, if you love parasites, parasitoid flies are just amazing, right? 

  Marty Martin  22:53  

  Well, in the movie Alien, right? I think you use this example, yeah, book, right?

  Jaap de Roode  22:57  

  Yeah yeah. So these flies, what they do is they lay eggs on the caterpillar. The maggots come out. They eat their way into the insides of the caterpillar. Eat it up when they're ready to turn into adult flies. They burst out of this caterpillar and then pupate and become an adult fly like the Alien movie. Totally gross if you don't like parasites, absolutely horrific. So what's interesting about these wooly bear caterpillars, unlike the Monarch caterpillars that I mentioned earlier, wooly bear caterpillars can eat a lot of different plants, so they have a very wide diet. And there are particular alkaloids in some of those plants that are detrimental, that they kill the flies. And the other really cool thing about these caterpillars is they have four taste receptors, and one of them tastes these alkaloids specifically. And what researchers have shown is that you can actually put tiny electrodes in these individual taste buds, which is totally amazing. And they did this with infected and uninfected caterpillars, and they gave them the alkaloids, and they can measure how rapidly are these nerve cells connected to these taste buds firing. And they found when they're infected, these taste but these taste buds go crazy and basically, so they respond more strongly. And the way to interpret that is that when this caterpillar is infected, these alkaloids taste better, it eats more, and now it kills the flies, right? So the caterpillar doesn't need to know what a fly is. It doesn't need to know what an alkaloid is. It doesn't need to know that when it eats them, it's going to get better. All it knows, you know, whether it really knows, all it's aware of is that these alkaloids suddenly taste really great. So I think that's a really good example of an innate behavior. But it's still intentional, because it starts eating more of it, and now it is really helping it so it doesn't need any consciousness about it. So I think a lot of examples are really baked into the body, baked into the genes.

  Marty Martin  24:49  

  Okay, and that's, I'm not going to beat up this issue, because this is not the focus, but I think that's the to me, this sort of innate solves the problem. It's just, you know, we've got great big complicated brains, and we can do behaviors in special ways that many organisms can't. But you very much made a great case that the taste receptors know. The brain maybe doesn't know, but an important part of the body does, in fact, know. I mean, it knows. Maybe it can learn. We could talk about other examples where learning is happening, but it's not happening in the skull. It's happening somewhere else in the body. 

  Jaap de Roode  25:22  

  Yeah, and I think we're learning a lot about the connections between the guts and the brain. But also, I would say what I find really intriguing is that we have this big brain. We're very, you know, conscious. We think we're very rational beings. But even in our case, we cannot override what our body is telling us sometimes, and in the book, I give the example of food poisoning. And so sometimes you eat something, you get very sick, and then sometimes we associate it with something we ate that wasn't actually what made us sick. And this is actually a big problem in the treatment of cancer in chemotherapy. And what doctors have learned over time is that when you give a particular meal, and people may say before they do this treatment, they want to have one last meal where they have everything they really like, whether it's French fries or chocolate or, you know, and then they do the treatment, they get really sick, and they know it wasn't the chocolate that made them sick. They know it's the chemotherapy, but they cannot stand chocolate anymore. They won't eat it. And so sometimes that big brain gets in the way, you know, or cannot even override what our body is telling us. So I think those innate mechanisms where our gut talks to our brain, and that's more, you know, the more primitive brain that's been around a long time, I think it's very important, and it's really involved. Because when you think about individual learning that's often associations. So what I just mentioned is a negative association. But you see a lot of animals, when they're sick, they eat something, they feel better, and the next time they feel sick, they seek out that thing that made them better. So you get these preferences and aversions that are learned, but very not consciously.

  John Drake  27:01  

  So if we can circle back to that last condition for thinking about medicating behavior, that it's costly, what does it mean that a behavior is costly in the absence of medication, and if it's not medicating itself, where does that cost come from? 

  Jaap de Roode  27:15  

  Yeah, so that's a really good question, and it's actually really hard to test in a lot of different systems. So where we have seen a lot of advancements over the last 20 years is a lot of studies on insects, where you can really much more easily do experiments, right? So when you study, say, chimpanzees, and you study how they medicate themselves, or you study elephants, it's really hard to do manipulative experiments where you purposefully infect them and then either give them the medicine or not, or you give them medicine where they're not sick and see, you know, what is their lifetime fitness? How many offspring do they get? Really hard with animals like that. But we can do that with caterpillars. We can do that with flies. We can do that with honey bees. And so, for example, in my own work with the monarch butterflies, when we rear caterpillars on really medicinal, highly medicinal milkweed. Some species of milkweed are so medicinal it kills all the parasites, but it also kills 90% of the monarchs that eat it, right? So it's a very clear cost. 

  Jaap de Roode  28:13  

  But we also know for chimpanzees, I mentioned the bitter leaf before that they use when they are infected with worms, they avoid it when they're not infected, and when they eat too much of it, it can actually kill them. So that's a very clear cost, right? Loss of health, even over a few days, could be detrimental or loss of appetite. You know, maybe they'll be less able to survive or maybe not have a child in that season, if you look at particular species. It's hard to quantify, much easier in insects than a lot of other species. 

  John Drake  28:44  

  So that's interesting. I mean, evolutionary biologists tend to see fitness as the currency for all costs. Thinking about clinical medicine, we think about it in terms of physiologic function and that kind of thing. And so I guess you're, you know, postulating that there's some link between these two. As you just said, even if you're ill for a few days, then you know that could have a negative consequence for your lifetime fitness. But do you think that's how sickness usually works out? I mean, most of the sicknesses that I medicate for, I don't think are life threatening.

  Jaap de Roode  29:14  

  Maybe not life threatening, but, but that may also be because of the way we live, right? I think if you live in a hunter gatherer society, as humans evolved in, then you know, being down the fever for four days may be really detrimental to your survivorship and your ability to get food or your ability to protect your offspring. You know, if I get fever for four days, I stay home, I let people at work know I'm not coming in, my fridge is still full of food. I think, so in some ways, I think, you know, when we look at wild animals that live more like when we were still wild, I think even a few days of disease can really be detrimental. You can also think even of, you know, hierarchy and social groups, when you're too sick to maintain that hierarchy, you may actually lose your place in that social group, lose your reproduction for the next few years. I think there's a lot of ways that this can play out.

  John Drake  30:11  

  I'm wondering if there might be some kind of macroecological or comparative hypothesis there? So run with me here, if you will. I'm thinking that, based on your example, there are some organisms who have a surplus of food, but perhaps most of their energies are about avoiding predators and other ones that have to be foraging all the time. Would you expect something different in terms of their self-medicating behaviors?

  Jaap de Roode  30:34  

  That's a really good question. I hadn't really thought about it yet, but I think that this is exciting to think about the new questions. But I surely think that there are, as you say, maybe you think about lions lying around most of the time, you know where some individuals get the food. So even when you're sicker, you can still get access to a meal. Whereas, if you are a prey species that is constantly being chased, and even the smallest, even also the sign of illness or weakness can make you that easy prey. It's well possible that those animals have evolutionarily invested more in defenses, whether that's medication or other defenses, I don't know, but I think that would be an interesting hypothesis to check for sure.

  Marty Martin  31:17  

  Are there any big patterns, broad patterns of sort of phylogenetic variation, of medicating behaviors? So for example, you know, I had a former tech in my lab, Sam, she wanted to do a project asking about the relationship between inter-specific variation and primate immunity and brain size. And it's really cool, because you could make the predictions that these things change synergistically, or they change in a kind of compensatory way. You could not have a great immune system if your brain behaviorally compensates for that. So anyway, we never really got into it. But do we? Do we see any kind of large scale variations? Or we just don't yet have enough data to even look?

  Jaap de Roode  31:56  

  We don't have enough data to look. It's still, you know, it's a field that has grown a lot, but it's still in its infancy, where, you know, you see more and more examples appearing. I think one of the issues, and this is really fun, this is something that John pointed out in reviewing the book for Science, is that, you know, the criteria that we mentioned earlier are very restrictive, right? When you say we only conclude in animals using medicine, when that animal recovers or benefits from it, what you're excluding is all the cases where the animal is trying to medicate but not succeeding, or where it's overdosing and actually killing itself. So I think we, you know, now maybe we're at the point where it's becoming accepted that animals can do this. We can start thinking about questions like that. But until now, it was really, you know, trying to persuade our colleagues that animals can use medicine. We have to show it works. But I think we have to be at a point now where we have to accept that sometimes it's not going to work. You know, we go to the doctor, we get a medicine. It doesn't work. We go back for another one. You think about antibiotics, for example. And sometimes it doesn't work at all, and we die anyway, right? So I think that is a really important thing. And once we accept that, we can really start looking across a lot of different species. 

  Jaap de Roode  33:17  

  I think, you know, one of the things that was really interesting for me in writing the book is that pretty much every story I tell in the book was an accidental finding. You know, people started looking at, you know, cats using catnip just to figure out why. Why are they doing this? What pleasure hormone is involved, and then find it has something to do with mosquitoes. You know, people in Mexico City started looking at cigarette butts just because they ran into them. They wanted to find out if, if all the trash in a city is really bad for the chicks. And the researchers studying chimpanzees, they were looking at the role of elderly chimpanzees in chimpanzee societies when they saw this remarkable behavior that suggested to them there was medicine. So I think now we're at a point, and I was having this conversation yesterday with a chimpanzee researcher, that we're actually at a point now where we can start looking for it, because we know it happens. And so with that in mind, yeah, we can start looking across the tree of life and then start doing those comparative analyzes. 

  John Drake  34:17  

  Yeah,  that's very cool. So if there's one thing that we know about hosts and their parasites is that they evolve together. And you've already told us a bit about learned self medicating behaviors. And we've talked a bit about innate self medicating behaviors, which presumably are due to some kind of evolutionary adaptation. But at the same time the parasites evolving, right? And we have all this theory about the evolution of virulence and how the virulence of the parasite or pathogen needs to be fine tuned in order to make sure that it actually continues transmitting. Some people would say it makes the host sick, but not too sick, for instance. And I'm wondering whether or not self medicating behavior by animals might play into that evolution of parasites and pathogens. Is there any evidence for 

  Jaap de Roode  35:09  

   So I don't think not yet, but it's one really exciting question is understanding if, if hosts keep on throwing all these defenses against their parasites, right, those parasites are under selective pressure to overcome those defenses. And we notice, of course, for immune systems, and we know it for genetic interactions, where you get these constant changes of kind of evading this immune system. And so I think that kind of thing is very likely to happen with medication. 

  Jaap de Roode  35:38  

  One of the things I'm really interested in myself in the monarch butterflies and their milkweeds is there's a lot of differences in what kind of milkweeds the monarchs use in different populations. Some populations, say in islands, say in Puerto Rico, the monarchs have a lot more access to this medicinal milkweed than in other places. As I actually want to go there, collect the animals, collect the plants, collect the parasites. And see, you know, in places where the monarchs use more medicinal milkweed are the parasites also more virulent? Or, you know, are they able to overcome those changes like we would expect? And so I think that's part of the story. 

  Jaap de Roode  36:17  

  I think the other thing that is really important, I think, about the way that animals use medication is that they're, unlike humans, you know, when we think about our pharmaceutical industry, we want to create these, these drugs, these medicines that are really pure and really based on a single chemical, whereas animals use these mixes. And I think that makes it harder for parasites to at least in terms of resistance, evolve resistance too. You think about honey bees and ants that use resin and that reduces bacterial growth and viral growth, fungal growth, but this consists of hundreds or thousands of chemicals, and so it's well possible that that makes it harder for the parasites to overcome that resistance. But again, these are all sorts of questions ripe for study now that we that we accept that animals can do this.

  Marty Martin  37:09  

  That's such a cool idea. Great to know that we have no limit of research ahead of us, all the PhD students yet to do the work

  Jaap de Roode  37:17  

  Well, and you know that that was part of the reason, also that I wanted to write the book. It wasn't just to show people how cool nature is, but also, you know, to show people there is, there's a lot of questions out there. And, we again, you know, a lot of the examples we have were accidental, but now we can actually start studying it. So if someone is interested,  in saying, you know, I want to know if a particular whether hyenas use medication, you know, go for it. We don't know it yet, so let's figure it out.

  John Drake  37:44  

  So just as we were talking, Jaap, it made me think about, well, we've got one example of a species that has used medicines and has resulted in evolution of the pathogens, and that's Homo sapiens. So we've got ample examples of antibiotic resistance, drug resistance to antivirals. And I'm wondering if there might be something that we could learn about human therapies by studying, you know, animal systems. Again, I'm thinking about your monarchs, and you've got some monarchs that feed on just one milkweed, and other monarch populations that feed on multiple milkweeds.

  Jaap de Roode  38:17  

  Well, and also, again, when they use the milkweeds, it's not one chemical in those milkweeds. Those milkweeds produce mixes of these bioactive chemicals. And so that's something that all these animals have in common. I think when we look at the problems we have about the,e you know, the quickness and the evolution of resistance, whether it's antibiotics, whether it's anti-malarials, right, I think a lot of those issues have arisen from the use of a single chemical at a time, and that's also why, when we think about drug development, there is a lot of talk, right about combination therapy now to actually have mixes. When you look at animals and you also look at traditional medicine, and I have talked to ethnobotanists, so people that really talk to traditional healers and say, you know, why? What are you using? Why are you using it? A lot of times, these healers don't know what is causing the disease. All they know is that what they're using works, but they don't worry about isolating a single chemical, right? It's, it's like, it's like a tea, or it's a potion. And so there's always the mixes they're using, and some of those things have been used for thousands of years, and it's so intriguing, right? Because then we say, Okay, so let's look at traditional medicine. What have they used for malaria? And then you find a particular plant, and then we're going to isolate all the chemicals, and then we're making artemisinin, and then you're gonna produce it as a single chemical, and now we have resistance to it, right? So I think that is the big lesson. I think that what animals and traditional healers tell us is don't try to make it so reductionist. It's not one chemical, it's the mix, and that can work longer.

  Marty Martin  39:57  

  That's really interesting. There's a colleague here that. You guys probably know that works at Moffitt Cancer Center, who's had some really interesting luck in the recent past with the treatment of prostate cancer by using rotations of drugs against the tumors, right? The same kind of idea, instead of the optimization against, you know, resistance of one, it's trying to deal with the Rock Paper Scissors problem. 

  Jaap de Roode  40:18  

  Yeah, that's right.

  Marty Martin  40:29  

  So this is a biology podcast. I think we maybe want to dip our toe into some of the different examples of cool things that various different species have done. I want to talk about bears because you sort of credit bears with the discovery of aspirin. Okay, so you have to explain that part, but a minute ago, when you mentioned fever, it motivated me even more to want to talk about bears, because it strikes me that fever is a complicated thing. In general, turning up your body temperature not too high and not for too long, but turning up your body temperature is protective. So aspirin as a medication in general, is a little bit weird relative to the other things that we're talking about, isn't it? How do bears use aspirin? Because they're sort of protecting themselves against the response to infection that itself is protective.

  Jaap de Roode  41:16  

  Yeah, I think actually when bears. So, bears are known to go in hibernation. And it's actually interesting, because bears have been very important animals for a lot of culture in the Northern Hemisphere. And bears going into hibernation and coming back in the spring, you know, there's beautiful anthropological stories about being reborn from Mother Earth, you know. And so it was a very important animal. But these animals are in hibernation for months on end, and they're essentially lying still for all that time. They're losing a lot of their body weight. They're becoming extremely stiff. So when they come out of hibernation, they're, you know, they have a lot of issues with their bodies. They're stiff, they're in pain, they're inflamed. And so one of the first things they do is they take the bark of willow trees and eat that, and that's got a lot of salicylic acid, which is anti-inflammatory. So it's not necessarily for the fever, but all the other aspects that they have in relation to this inflammation and the stiffness and all of those things. 

  Jaap de Roode  42:15  

  So people have copied that behavior. And it was really in the 18th Century that in Britain it was rediscovered that you could use this bark. I think, in that case, it was to reduce fever. And then the pharmaceutical company bear different type of bear, they then developed that salicylic acid, and actually changed the formula a little bit to reduce the side effects, because that a lot of side effects at first. So we're still using that, but I think, yeah, so I think the bears didn't necessarily use it against fever. It was more for other inflammatory reasons. But what I love about it is that it's one of those cases where we talk about one of the big triumphs of the pharmaceutical industry that it looks like that originally came from bears. That's not saying that, you know, in the last 150 years, people learned it from bears, but the fact that you could use that bark came originally from traditional healers that then had looked at animals, specifically these bears, to get that knowledge.

  Marty Martin  43:14  

  Yeah, that's amazing. Do other wildlife use bark for aches and pains or?

  Jaap de Roode  43:19  

  Oh, it's really interesting. I was just at a talk in anthropology today, and this is Elodie Freyman n. She studies self medication and chimpanzees, and she actually dedicated a whole study to looking at bark eating in chimpanzees. And so the leading hypothesis has been that chimpanzees do this when other food is not very available. It's like a backup food. But she found that they eat it even when it's like the season where most fruits are around. And so they often eat bark of particular species. They eat a lot of it. And then she found that the traditional healers in those local areas also use it against all sorts of infections, so that that often tells us that there's probably something about it, bark, eating. So yeah, there's other species dare do it as well, chimpanzees, for sure.

  John Drake  44:06  

  So yeah, I'm glad that you brought up chimpanzees, because, you know, last week, we really lost a giant in this field, in Jane Goodall. And you write in the book that she noticed that chimp dung sometimes contains leaves of a plant called Aspilia pluriseta. Did I say that right? 

  John Drake  44:21  

  Yeah. 

  John Drake  44:22  

  I was wondering if you can tell us more about that story. 

  Jaap de Roode  44:25  

  Absolutely. And yeah, first of all, a big loss to science and to nature and to just, you know, getting encouraging so many people to actually go into the sciences and really think about our place in nature. One of the really important things is that, you know, when she started studying chimpanzees, she'd have any education in it, which is amazing, too. And she said that actually helped her in looking at these animals, not from this reductionist Western scientific point of view, but more as individuals. And so she had that in common with the Japanese primatology that have traditionally much more, looked at these animals as having personalities and allowing them to see these animals as individuals that do interesting things. Rather than giving them numbers, they gave them names. And that's what Jane Goodall did as well. And that is how she also discovered, you know, the use of tools. And so she saw gray beard was one of the chimpanzees she studied, you know, using this, basically a tool to eat ants or termites. And the same with the Japanese primatologist, they could discover culture in primates, again, something that we thought was completely human. 

  Jaap de Roode  45:33  

  So I think in that context, it's really interesting that she also, in the 1960s when she was studying chimpanzees, she often found that when you look at the poop of the chimpanzees, that there is these whole undigested leaves in there. And that was really curious, and she wasn't really sure what that was. But then in the 1980s there were other primatologists, including Mike Hoffman from Kyoto, where he studied this. And he studied it in collaboration with traditional healers, which was really important, because, again, they they had this idea animals can use this, this medication that wasn't that strange to them, but, but all that research ultimately showed is that the chimpanzees, when they swallow these leaves, it's called leaf swallowing. They don't bite it. They don't digest it. They swallow the whole thing. And what all those leaves have in common, including the species you just mentioned, but chimpanzees use, like, use about 30 species, of them or so. They all have in common, a really, really rough leave, so rough, in fact, that it gets used as sandpaper. So the locals use it as sandpaper to sand the handles of their machetes, and it works like Velcro. So when the chimpanzees swallow it, it goes through their guts, and then they see, when you look at the dung, there's parasites, like worms stuck to these little hairs on the leaves. And so that's probably that's why they're using it. And even more exciting is that different chimpanzee groups fold those leaves in different ways. As you can imagine, somewhat, the leaves are actually really big, and it's really hard, as you can imagine, to swallow a leaf. So they fold it up in a smaller piece, then swallow it. And different groups of chimpanzees fold the leaves in different ways. So there is medicine and there is culture. They use it as a tool, all these things that used to be human, and these animals use it too.

  Marty Martin  47:19  

  Wow, 

  John Drake  47:19  

  Wow, that's fascinating.

  Marty Martin  47:20  

   Do people use these then? I mean, we're special primates in so many ways, but are there human populations that do or have swallowed whole leaves this way?

  Jaap de Roode  47:29  

  I don't think so. I'm not aware of that. That's yeah. So that's something that we haven't copied from these chimpanzees. And maybe we're just not very good at swallowing such a big thing.

  Marty Martin  47:39  

  I'm not volunteering for that experiment, even if this is a typical behavior, historically, I will pass. 

  Jaap de Roode  47:45  

  But our pets do, right? And not that they learned it from the chimpanzees. But when we walk our dogs, and our dogs eat grass, and our cats eat grass, it's actually remarkable how little research has been done on domestic pets for this behavior. But when you look at wild carnivores, you know carnivores are supposed to eat meat, right? But when we look at wolves and mountain lions and jaguars, they often eat grass. And it's a similar story. They choose grass that's really rough, really sharp. They eat it, and they either throw up or they poop, and it often has these parasites in it. And I love that, because it gets back to something that we were saying earlier, you know. So I have two dogs, and they do this as well. My dogs don't have worms, but they do sometimes eat pieces of Lego or Barbie doll heads that kids leave around. Right, so again, what it shows is the animal doesn't feel right. They don't know what it is, but they still have this response of eating this grass, and then they throw up, and out comes the Lego piece. So yeah, they respond to the symptoms, not to the parasite necessarily.

  Marty Martin  48:48  

  Alright, one last Natural History anecdote. I can't pass up the chance to talk about house sparrows. You briefly mentioned your colleague, Montserrat Suarez-Rodriguez and others in Mexico. So, you know, maybe say a little bit more about what these urban birds are doing, because they were, they were quite surprised, and I was really blown away with the sort of sophisticated behavior of these little animals.

  Jaap de Roode  49:12  

  Me too. I think it's amazing, and I love the story for many different reasons. One of the reasons is that this was an undergraduate student going to university and discovering something exciting. And that's also what I wanted to clarify in the book, is that this kind of science is for anyone. It's not for old, bearded, you know, professors like us, right? It's for everyone. So she joined the University really trying to figure out what is all this pollution doing to these nests. And so she started studying the nests of sparrows and finches that they make on the university building. So it was a really easy study system to look at. And then so she was starting investigating what these birds put in the nests, and she found all this white, fluffy material in them, and she couldn't really figure out what it was. But then one day, it was raining, and she could smell the smoke, and that's when she realized that the white, fluffy stuff was the cigarette butt filters that the birds had collected and pulled apart and put it in the lining of their nest. And that's funny, too. Then she went to her advisor to tell him that, and he didn't believe it, and she had to make the nest wet, and he could smell the smoke, and he said: "Oh, it's cigarette butts." It's like, "yeah, I told you that." It sounds familiar to us. We're all advisors, so we know how that goes. 

  Jaap de Roode  50:23  

  But she also found that when the nest had more of these cigarette butts in them, some of them had, like, over 30 of these cigarette butts in them, that there were fewer ectoparasites, so lice and mites and ticks that suck the blood of the chicks. Now that still doesn't mean the birds were using medication. Maybe they just love the cigarette butts, and as a coincidental side effect, it also reduced these parasites. But then she did this experiment, and that's fascinating too, because what you want to do is you want to manipulate a nest. So you go out there, there is a nest, but when you manipulate it, the birds reject the nest. So it took her two years to figure out how to replace the lining that the birds make with the lining she made without them rejecting it. But when she figured that out, she could then do that and add life ticks or dead ticks, right? And so life ticks are going to suck the blood of the chicks, dead ticks are not. And she found the birds in nest with the life ticks started collecting more cigarette butts and therefore their chicks did better. They had higher fledgling success. They survived better. And so they really showed that in response to these ticks, the birds use these butts as medication. Now the other thing is that this doesn't mean we should all start smoking and throwing our cigarette butts on the floor. And this goes back to a question we said earlier. Now, what is medicine, there are side effects too. So they also found that when you looked at the blood cells of these birds, they had some malformations as well. So it helped against parasites. But it's not cost free. I mean, there are detrimental effects.

  John Drake  51:58  

  So yeah, obviously, sparrows haven't been coevolving with cigarette butts for centuries and centuries, they learn this behavior somehow, right? What is our best guess about how these animals are learning these new behaviors and then passing them on?

  Jaap de Roode  52:14  

  So during the 1980s when these experiments that we mentioned about the chimpanzees, when they were happening. Researchers also found that a lot of birds put all sorts of things in their nest, and oftentimes they put a lot of aromatic plants in their nest, so plants that are really smelly. And they had a lot of hypotheses, but one of them was they did it to keep parasites away, but they didn't do the beautiful experiments that the researchers did with the cigarette butts. But one of the plants that birds often collect is the tobacco plant. And so and I asked the research in Mexico City this, when I talked to them, I said: "Are you worried, you know, say the university has a successful public health campaign. Everyone stopped smoking. What are these birds gonna do?" And they said: "Well, the birds will just go back to collecting the plants that they were collecting before they realized there was a much easier way to get these chemicals." So it's actually the nicotine itself plays a role. And so nicotine is a really important anti- or an insect or arthropod repellent, and so that's what they're probably going for in these cigarette butts. There's other chemicals as well that they respond to. But the other thing is, you look at these birds, and they're all in this building, and all these birds are checking each other out, and so they know what each other is doing. And so what the researchers thought is that one bird probably started collecting these cigarette butts, and then other birds copied that. And you see that a lot as well, that animals can learn from each other by mimicking each other and learning from each other.

  John Drake  53:44  

  Yeah. So another example of a transmission of culture?

  Jaap de Roode  53:49  

  Yes, exactly, yeah. It is very cultural, because there are some, you know, there is now. I heard some stories about pigeons doing the same in other cities. So it happens every now and then. But yeah, you often see that. And, you know, if you think about the culture of the blue tits in the UK that started opening the milk bottles, but the way they did it was different region by region. So yeah, you get a few of these clever ones, and everyone else copies them.

  Marty Martin  54:15  

  Yeah. So how do you think the idea of neophobia or the fear of novelty or, I mean, we could flip it on its head and call it neophilia. I think there's only been a couple of examples of that, besides the interest in novelty. I mean, do we think that that plays some kind of a role in the sparrows or anything else? Is there any evidence to that effect?  

  Jaap de Roode  54:35  

  Absolutely. So it's actually a lot of animals are very neophobic, so scared of the new, scared of the novel, right? And so they're actually very conservative with what they eat, which makes a lot of sense when you think about it, because you know, when you're a herbivore and there's all these plants, a lot of them are very deadly, very toxic. And this is also, for example, why it's hard to kill a rat, right? If you have a rat problem, you just start throwing poison around. They're not going to eat it. So what you have to do is, you know, put something out that they like, and then once they eat it, then you add a little bit of poison. So not that I say we should poison all the rats, but you're overcoming that neophobia. And so, but, but we see with a lot of animals, when they are sick, they are less neophobic, and they're way more prone to trying new things, and that allows them to, you know, when they have these symptoms, it allows them to nibble on a few leaves that they haven't tasted before. And oftentimes they start being more interested in bitter tasting foods. And a lot of medicinal foods, a lot of medicinal plants are bitter. They taste bitter. So they become less aversive, to trying new things, and then when they discover some of those are bitter, and they start having these associations. So now they have learned next time when they're sick, they're more likely to go to that particular plant and eat it to get better.

  John Drake  55:54  

  So, I don't mean this question in any negative sense, but I'm curious whether or not these medicating behaviors are really just curious natural history anecdotes, or if they might have some implications for us as humans in our practice of medicine, especially, I'm interested in whether or not you know pharma companies or public health professions. Have you know mobilized teams to do some research on this? 

  Jaap de Roode  56:20  

  Yeah, so I think, I think it all started with anecdotes, but I think we now have really good scientific evidence, both in observational studies and experimental studies, to show that animals can use this medicine and we can learn a lot from them. So before I talk about a pharmacological and, you know, the human applications, it's even when we think about how we keep our animals. And, for example, the livestock industry, we don't let the animals assemble their own diet. We don't let them medicate, even though they still have those abilities. Instead, we give them this mixed ration of food that has all the nutrients that we think they need, but it doesn't include any of the medicines. So then we give them antibiotics and anti-emetics and this causes all of this resistance. So we can do much better. There even introducing some medicinal plants, and they can maintain their own health. 

  Jaap de Roode  57:09  

  But certainly, when we think about human applications, you mentioned earlier, we have all these problems with resistance, right? So we have antibiotics, they're losing their efficacy. We have anti-worm medication losing its efficacy. And so I think we're always on the lookout for new drugs. And I think that's definitely something the pharmaceutical industry agrees with. Always looking for new drugs. And of course, there's a lot of hope that when we start from scratch, making new chemical formulas that have never existed, we can get there. But I think by also looking at animals that have used some of these medicines, probably for millions of years, we can discover things that are already out there and that we can start using and maybe use them in the way that animals use them. Not completely. I'm not saying we should all start swallowing leaves and eating grass, but the idea of maybe using mixes of different chemicals could go a long way. And what you see now is because it's now accepted that animals use medicine. I spoke to researchers in Congo that are specifically studying bonobos and gorillas and chimpanzees, cataloging kind of the weird behaviors what do they eat that they normally don't eat, and then take those plants to the lab, extract the chemical fractions and test them against bacteria, malaria, parasites. So I think there is a lot that we could gain. We don't have to reinvent the wheels when animals have already used some things for millions of years successfully. 

  Marty Martin  58:37  

  Yeah, can you maybe say a little bit more about domesticated species? I'm glad you brought that up, because, and I love your way of, sort of presenting this idea, juxtaposing Darwin's take on domestication versus Alfred Russel Wallace's take. And I don't know if we should blame Wallace for sort of, you know, to all think that domesticated species are stupid. They're very much not. And I think my favorite example was where you say that when we let beef cattle choose their diet, they make a lot more beef. 

  Jaap de Roode  59:05  

  It's amazing. 

  Marty Martin  59:06  

  Yeah, it's totally I've never heard of that before. 

  Jaap de Roode  59:08  

  It's amazing. Yeah, and I don't want to put Wallace in a bad light. 

  Marty Martin  59:11  

  Of course

  Jaap de Roode  59:12  

  I love Alfred Russell Wallace, and I think we should mention a lot more. As a co-discoverer of natural selection with Charles Darwin. I just find it interesting. He wrote this beautiful essay in 1858 that kind of spurred Darwin on to finish his book. And so he had this idea of domestication, you know, where Darwin said domestication, beautiful example of how natural selection can work. If we can select for all these weird pigeon breeds or weird dogs or weird vegetables, nature can do it too. And Wallace said more, "Well, we have created these things, but are utterly useless". And I felt personally offended when he brought up the example of a poodle, because I have a mini poodle and these things will just never survive in the wild. It is absolutely right. He's absolutely right. But it also means that it doesn't mean that these animals have lost all their abilities. Is like we sometimes say. So I think sometimes we as humans think we have domesticated these species. We know better, but it's good for them than they do themselves, and that has resulted, you know, in us giving them really impoverished diets. 

  Jaap de Roode  1:00:15  

  And yeah, the example you mentioned, so this is research coming out of Utah State University, where they've worked for decades now, on sheep and goats and cattle. But yeah, they had an example with cattle, where they had a group that were given the mixed ration, another group that were given the same ingredients for that mixed ration, but separately so those cattle could make their own diet. And over the course of two months, they found that in that group, every individual calf was eating a different diet, which makes sense. You know, the three of us probably eat completely different diet, so just individual differences, so they're not all the same, but on average, they ate 20% less. And what that means is that the production of a kilo or a pound of beef is 20% cheaper, but also you get less greenhouse emissions, greenhouse gas emissions, which is just amazing. And really the lesson that we can learn there is that these animals are good at assembling their own diet. When we give them a mixed ration, they keep on eating so much until they have reached what is limiting them the most. But whereas they can pick between the different foods, they just eat less of the stuff they don't need anymore, and they keep eating the stuff they do need, right? So they stop overeating, we basically make them overeat. And so if we let them choose, they eat their, you know, a smaller amount, and everyone wins.

  John Drake  1:01:39  

  So how universal, though, do you think this is? I mean, it seems to me that, especially among domesticated animals, dogs, cats, maybe certain farm animals, when given the choice, they will sometimes overeat, right?

  Jaap de Roode  1:01:53  

  Yeah, and I think we do that too. But I do also think that when we give them these pre-mixed diets, you know, they're probably all over it to some extent, because they eat more of, you know, some things they keep on eating until they get what limits them the most. I think that in addition to that, there's also an animal welfare, you know, question there. Just think, you know, I have extremely spoiled dogs. It's really, it's really bad. They love variety, and they get really angry with me if I give them the same meal twice, you know, two days in a row. They really love their variety. But, yeah, I think, you know, it's just a question. Imagine eating kibble for the rest of your life for breakfast and dinner every day the same. I don't think it would make us very happy. I don't think it makes them happy. And it's not necessarily the healthiest. But yeah, there will always be some animals, and I think that's the other thing, John, that we don't have a good sense of yet, of how much variation is there, and how good animals are in assembling their diet or in medicating, right? Some animals are probably really good at it, and some animals are probably really bad at it. And again, that's something we don't know yet that we really have to focus on.

  John Drake  1:03:07  

  So we have talked a little bit about how, you know, in modern pharmaceutical medication, we've created all these medicines that do have negative side effects, sometimes single chemical drugs, you might even include ethanol in that list, but others as well, that sometimes people develop addictions to. Are there any examples of wild animals developing similar kinds of dependencies?

  Jaap de Roode  1:03:33  

  I'm not sure. So there are definitely a lot of anecdotes of animals using chemicals that, you know, make them drunk or make them euphoric or stimulated. I think we're not at a point yet where we really understand if they keep on doing it because they become addicted. You can make animals addicted really easily in the lab, and it's a lot of addiction research on mice, for example, or even primates. How often that happens in the wild, I don't know. There's a lot of talk about, and this is really having a comeback right now, you just mentioned ethanol. You know, it's always, you know, a lot of people find it fun to think about drunken elephants and drunken chimpanzees and stuff. And we see that, and then, you know, and that's funny too, because the question is, are they doing it just for fun, or are they doing it to get enough food? Is there a lot of calorie intake there? And so we don't know that yet. And I think part of this is that hasn't been studied in enough detail, it's all these anecdotes right now. But how much addiction is a problem in the wild? I don't know. That's a really good question.

  Marty Martin  1:04:38  

  Episode One of Big Biology was with Robert Dudley and his book The Drunken Monkey. So this is something long time ago in our past that we talked with Robert about. So yeah, what would you what would you do next? You're the director of the new NIH division on animal medication behavior. What are your sort of where are you putting your money? In terms of the most interesting results?

  Jaap de Roode  1:05:01  

  Are you just offering me a job? What's the salary?

  Marty Martin  1:05:05  

  Sure I have no authority to do this. Kind of thing, but yes if you want to take it.

  Jaap de Roode  1:05:08  

  No. I mean, I think that would be really cool. I think there's a lot of interesting questions to be asked. I think a lot of the ones that we have mentioned so far. I think, you know, from an NIH point of view. If you really think about the public health or the individual health aspects, you know, the question, what can we learn, and what do we need to do to really discover these new treatments by studying animals? I think that would be a big program call that I would do, but I would also, you know, really think about, you know, what could you fund in terms of understanding the individual variation of how animals use medicine, how good they are at assembling their own diets, how that can really shape the way we think about our own medicine? Oh, man, it would be fun. Yeah, it depends on the budget you're giving me, but I can imagine some really, really cool project. Also, you know, a lot of training grants. And I'm thinking about, you know, expedition grants for undergraduate students, you know, summer programs to really get into this field, send them to all sorts of places around the world. Oh, and this is one of the things that we really, really need to figure out, is how much animals use medicine in aquatic and marine environments. Everything we have talked about today has been terrestrial, right? Animals living on land. But you look at the sea, my goodness, there are so many amazing chemicals in there, but we virtually know nothing about how animals use them and what we can learn from them. So I would probably have a whole subdivision at the NIH for for marine applications, marine medicines.a

  Marty Martin  1:06:46  

  Yeah, and I think you would have a lot of students signing up for that one, so you'd probably have no issue there. Okay, so just one more. One more question. Very early, you mentioned dose as a kind of element of all of this. And, you know, it doesn't probably take a lot of what we would call medications to dip into danger. How do we think about that, and how much do we know about the dose side?

  Jaap de Roode  1:07:10  

  Yeah, I think that gets back at the question of how, how good are animals at dosing themselves, and is there individual variation? But we, we definitely know in general. You know, it was Paracelsus during Renaissance time, really, the father of toxicology, who said it's the dose that makes the poison. And, you know, you think about something as simple as caffeine, right? So caffeine is, you know, we drink coffee and it tastes good, so you can see it kind of as a food. But you can also drink the coffee, and some of us use a little bit more to stay awake and alert. So you can see that as kind of a drug. But you can also poison people with caffeine. You know, if you drink too much, or you inject it into your bloodstream, it can kill you. And so I think this is true for a lot of the things that we have been talking about. I mentioned the heart poisons, the cardinalites and milkweeds. They can kill monarchs, but they can cure them at the right dose. So I think that that is going to be a really important thing. And I think part of the reason we mentioned that too is the neophobia that animals try to avoid new things, that they're kind of scared of new things that may have to deal with the dosing as well. So you often see when they start using these medicinal plants, they take little nibbles. It's not like they eat a huge amount at first. So I think there may be a part of learning, especially for animals that can do that individual learning, that they learn to use the right dose and are very careful and not overdosing. But again, I think some individuals probably gonna overdose. 

  John Drake  1:08:38  

  Well, yeah, it's been really fun connecting with you today and hearing about all this interesting research. I wonder if there's any last thoughts that you would want to share with our listeners?

  Jaap de Roode  1:08:47  

  Well, I think, you know, we have mentioned a few of the reasons why, why I wrote the book was, you know, first of all, nature is amazing, and animals are amazing. I want everyone to know that. But also, like I said earlier, to show that this kind of science is for everyone you know, and that's why I made a big effort in the book to to also really describe the people that do the research, whether they're in Congo or Japan or Mexico or the United States, they're everywhere, and oftentimes it's young people that are just really open-minded. I think that's really important. But the final message I wanted to send with the book is to say, look, there is this huge pharmacy out there. And it's not just a pharmacy. There are pharmacists. So we have plants, fungi, we have animals, and there's so much wisdom out there. And I'm really worried about the state of our planet right now, and you see this with traditional healers that cannot find the plants anymore that they used to use. We see the same with animals. We're losing so much nature, and by doing that, we lose the pharmacy, but we also lose the pharmacists. And if there is something to learn, we really need to preserve that. And that can sound overwhelming to a lot of people, but I think if everyone does a little bit. I think that's what Jane Goodall said. You know, if you're gonna make you can choose how you're gonna make an impact in the world. And she also said that if everyone does a little bit together, we can make a big change. 

  Jaap de Roode  1:10:11  

  And this is partly why I'm involved with the Rosalind Carter Butterfly Trail, which is this. The idea is very simple, it's less let's recreate nature. Let's plant native plants. We look at people's front lawn. You know, surprising thing writing the book, the biggest crop in the United States. It's not corn, it's not soy, it's lawn, just the green lawns in people's gardens and on golf courses. It supports absolutely nothing. It takes huge amounts of water, pesticides and fertilizer, and it doesn't give anything. And if all of us just replace 10% of that lawn with native plants, we recreate nature that helps the pollinators, it helps our pets, it helps birds. We can recreate a lot of nature. And so we can do a little bit, and together, we can do a lot to preserve that pharmacy and the pharmacists that we need and that we can learn from.

  John Drake  1:11:02  

  Well said.

  Marty Martin  1:11:03  

  Excellent. That was a great way to end, yeah, thank you so much Jaap. We really appreciate it. We wish you the best of luck on the book.

  Jaap de Roode  1:11:09  

  Thank you so much. It was a pleasure talking about it.

  Marty Martin  1:11:12  

  Thank you for listening to this episode. If you like what you heard, tell us BlueSky, Threads, LinkedIn, Facebook or Instagram, or leave a review wherever you get podcasts, we really do read them all.

  John Drake  1:11:34  

  And if you didn't like something, we want to hear that too. All feedback is good.

  Marty Martin  1:11:37  

  Feedback special. Thanks to Steve Lane, who manages our website, and Molly Magid for producing the episode.

  John Drake  1:11:42  

  Thanks also to Caroline Merriman for social media support. Brianna Longo for our amazing cover art, and Clayton Glasgow, our blogger. Check out his work on our Substack page.

  Marty Martin  1:11:50  

  Big thanks as well to the College of Public Health at the University of South Florida, our Subtack of Patreon subscribers and the National Science Foundation for support.

  John Drake  1:11:59  

  Music in this episode comes from Podington Bear and Tieren Costello.

  Marty Martin  1:12:03  

  Thanks again for listening, and we'll see you next time on Big Biology.