This Podcast Will Kill You - Ep 91 Myxomatosis: Down the rabbit hole

Episode Date: February 22, 2022

Invasive rabbits so numerous they form a “gray blanket” across the land. A killer virus, intentionally released to keep the bunnies at bay. An ensuing evolutionary arms race with no end in sight. It sounds more like the premise of a bad sci fi movie rather than a textbook case of biocontrol. But truth, especially in this case, is stranger and even more fascinating than fiction. If this is the first you’re hearing about myxoma virus and its place in the long history of European rabbits in Australia, get ready for a gripping story filled with rabbit facts, discussions about what drives pathogens to be deadly or benign, and philosophical musings about the situational difference between pest, pet, and keystone species. That’s right, we’re heading deep down the rabbit hole with this one.  See omnystudio.com/listener for privacy information.

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Get started at redfin.com. Own the dream. No one would believe the mischief the rabbits are doing unless they could see it. The sheep farmers have not tried to clear them, and now many of the runs are so bare that there is not grass enough to feed the rabbits, let alone the sheep. The consequence is that the rabbits are traveling in thousands in search of food. Last Friday morning, soon after sunrise, I met a swarm coming from the hills. I never saw such a thing before. The ground was scarcely to be seen for about a mile in length. Five weeks since I could not find a rabbit on my land, but since then we have killed thousands.

When the sun is hot, you can go along the fences or any place where it is shady and kill hundreds with a stick. Today has been cool, but still I several times killed two or three at a blow. The paddock stink with the dead ones. Immediately prior to the liberation of mixomatosis, a combination of circumstances had led to the buildup of rabbits to very high levels over much of most of their range, and the situation in many areas could only be described as desperate. The change has been almost miraculous.

The landscape in some areas has been virtually transfigured. Hills that had been grazed to the soil for decades and whose slopes appeared gray and red on the horizon are now clothed in grass. The broad margins of the country roads, lying outside the boundary fences of grazing properties, tended to carry dense rabbit populations and, as often as not, showed it in the poverty of their ground cover. It is now usual to see tall grass to the road's edge. Looking over the fences, it is now very rare to see a paddock without a dense and healthy pasture. Wow. I love it and those two passages just got me so excited for this episode. It's very interesting to kind of see like a very clear before and after quotes. Yeah. Those two quotes I lifted from a book called the biological control of vertebrate pests. And they are both about the topic of today's episode.

Mixomatosis. Mixamotosis. The Radiohead song. So we're going to talk in this episode all about Tom York and what inspired him to write the song Mixamotosis. I have no idea what you're talking about. Erin. Okay, Mixamotosis is actually the topic of today's episode, but it's a virus that affects rabbits. And it also happens to be the title of a Radiohead song.

Wow. I definitely did not know that last part. I listened to it in prep for the recording today. Nice. We should try and get the rights. You know. Bloodmobile, can you write us a knockoff? I feel like I should introduce myself before we begin the rest of this introduction.

Maybe we should. Hi, I'm Erin Welsh. And I'm Aaron Amman Updike. And this is this podcast. podcast will kill you. Yes, it is. Welcome. If this is your first time here, we usually do things in a different order. And maybe a little bit more clean and a little bit more organized. We're just so excited about mixomatosis. And I think you were really excited to tell me about Radiohead. I really was. I really was. Did you know that I wasn't going to know? I feel like you did.

I gave it about a 5545. Okay. Okay. Yeah. But yes, a rabbit viral disease is what we're talking about today. It's going to be great even if you think you don't like animal viruses or you don't like rabbits or you do like rabbits. You're going to love this episode. I think so too. This is like if you just clicked on this out of sheer curiosity and you're like, okay, now I'm having my doubts. This is a rabbit disease. Yeah.

I promise. I think this is one of the most interesting. and important stories about disease that we have covered on this podcast because it covers so many different topics, so many different concepts. Yeah, it is, it is such a good story, promise. It is. But we have some business to take care of. We do. It is first, quarantini time. It is. What are we drinking this week? We're drinking Bunny's Bug. Ha ha ha. Get it? Bunny's Bug is a tasty little drink that has hop water because bunnies hop. I don't know if we needed to explain that, but...

I like it, though. I like the explanation. It has lime juice. It has mescal. It has simple syrup. And it has some grapefruit juice. Yum. Delish. We'll post the full recipe for that quarantini as well as our non-alcoholic placebo-rida on our website. This podcast will kill you.com. and all of our social media channels. Oh, is it my turn to do the website information now? Okay. It is. On our website, you can find transcripts.

You can find our bookshop.org affiliate account. You can find our Goodreads list. You can find links to music by Bloodmobile. You can find all of the sources for each one of our episodes. You can find links to the promo codes that we mentioned in our ads. merch we've got transcripts we've got yeah we got it all that's got to be it that's got to be it

okay well then should we you know get into it let's do it okay we've hyped it enough you think I hope we haven't overhyped it oh let's find out right after this break

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That's Q-U-I-N-C-E.com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. Fair warning, listeners, I am starting off this biology section kind of intentionally withholding details for later dramatic effect. So let us begin. Mixomatosis is a disease caused by the microintosis. Xoma virus, which is a member of a family we are familiar with here on the podcast. It is a pox virus. As in smallpox, I don't think we've covered any other pox viruses. I was just going to ask. I can't remember. Oops. But anyways, yeah, this is a different genus of pox virus. This is a lay poroxy pox virus.

And smallpox is an orthopox virus, if anyone cares. But, All of the pox viruses are double-stranded DNA viruses. They have pretty big genomes. And the virus itself, if you look at it under a microscope, is shaped like a brick, which I just think is funny that every single paper described it as a brick-shaped virus. Interesting. It is. Huh.

The pox virus, mixoma virus, replicates in the cytoplasm of cells. And it's a really fascinating virus because it has a lot of proteins that interact with the host immune response that become really important in terms of how much disease we actually see in its various hosts. And mixoma virus causes disease only in rabbits. It infects a large number of species of rabbits. But as far as I can tell, it doesn't cause clinical disease in any of the other hosts that it has been tested in other than rabbits, and I think one species of hair.

which are all called lagomorphs. I learned so many new words researching this episode. But mixoma virus, interestingly, can replicate in vitro, like in a petri dish or a cell culture bottle, in cells from many, many different host species, including human cancer cells, which it turns out are particularly good at letting mixomavirus in and letting it replicate. Interesting. Very. and I'm throwing that little tidbit out there and then just going to leave it to dangle and circle back to it at the very end of the episode.

Okay, I was all poised to ask a question, but I will restrain. Okay, but today we're talking about rabbits. So this mixomavirus causes the disease known as mixomatosis in rabbits and hairs. And specifically, it causes the severe disease that we know of as mixomatosis in the European rabbit oryctalagus cuniculus. if I'm saying that right. Do you remember the books, Bonicula? No. It was like about a vampiric rabbit that sucked the juices out of vegetables. I do not. I've never read that book. Really? It was like a series of books for kids. But I remember like when I saw the scientific name of the European rabbit, I was like, oh my gosh, that's where the Nicula comes from.

That's very funny. I have not read it. those books. I'll put them on my goodreads list. They're wonderful. Okay, so let's go over what this disease looks like in this European rabbit. So the incubation period tends to be about four days. And the initial symptoms, I'll kind of go over what this progression of disease looks like. Initially, after that, about four days after infection, the symptoms are generally redness in the eyes, so kind of a conjunctival inflammation, and an elevated body temperature.

What temperature are rabbits' bodies normally, you may ask? I would ask, yes. Yeah. Well, I did Google it. It's about 102 to 103 Fahrenheit, which is 38.9 to 39.4C. So they run a little hot. This virus makes them a little hotter. And then following after a few more days after initial infection, after these kind of red eye symptoms, these secondary lesions appear.

They're often called cut. Papular lesions, basically just little lumps, little skin-colored lumps on the rabbits that appear kind of throughout their body, but most prominently at the bases of their ears. They also get swelling in the anogenital region, almost universally. And then they begin to have discharge, both kind of a clear, like cirrus discharge, as well as a mucopurulent or kind of pus-filled discharge from the nose and the eyes. And then by days eight to ten, these poor little rabbits will have a very, very swollen face, droopy ears because of all the swelling at the base of their ears. They'll have severely swollen eyelids and really goopy eyes, goopy noses that get so filled with

gunk that their tiny little nasal passages get clogged. And then all across their body, like throughout their body, they'll have these little, anywhere from a few millimeters, to a few centimeters, these little skin swellings across their body. And their anogenital region will become really, really swollen, especially the testicles. And then their breathing will become more difficult and labored. They'll have this kind of sturder, which is that like gasping inhale. And they generally die between 8 to 12 days following infection. And so that's like 8 to 12 days after they first get exposed.

So it's only like a period of four to eight days. Wow. Four to eight days. Yeah. It's a very, very rapid course of disease. And mixomatosis, this disease classically, has an almost unbelievably high mortality rate in the European rabbit. 99.8 to 100% mortality. This is along the lines of, I think just rabies and preons are the only.

two diseases that match this kind of mortality that we've ever covered. Yeah, that we've covered so far. Yeah. Woof. Yeah. And so the virus, this mixoma virus, is present in all of those goopie secretions as well as in all of those skin lesions. And it's very easily transmitted to other rabbits, potentially by direct contact,

but mostly by various biting arthropod vectors. But even though this is a virus that's transmitted by vectors like mosquitoes and lice or fleas. And especially in terms of epizzootics or these outbreak scenarios, it does seem like vectors, especially mosquitoes, are pretty pivotal in terms of large-scale transmission. Like without them, these outbreaks don't really spread or don't spread as quickly. Oh, yeah. But the virus does not rely on mosquitoes for. its life cycle or transmission, it doesn't infect or replicate in mosquitoes the way of most, if not, I think all of the vector-borne diseases that we've ever covered on this podcast do.

What that means is that this vectoral transmission is just mechanical, right? Which means that the virus has to be in very, very high titers in the cutaneous lesions, these skin lumps on the rabbits in order for the mosquito or the flea to have enough virus on its mouth parts to then transmit it to the next rabbit. Yeah. Do you know what the infectious doses like in unselected rabbits? Yeah. I don't know exactly, but I do know that it seems like critical levels in the skin tissue

are like 10 to the seventh viral particles per gram of rabbit tissue. So that's like a little over, what, 10 million or so, viral particles per gram. So really, really high titers are necessary for this to be efficiently transmitted. Okay. Yeah. And I'm assuming also that the mosquito has to bite one of the lesions or like pick up and where the gunk is. Exactly. Yes.

And that is why it's thought that especially those base of the ear swellings might be very important for viral transmission because that's a commonplace for mosquitoes and other vectors. to bite the rabbits. So now anyone who's listening who knows the story of mixomatosis knows that that description that I just gave of this horrifying lethal disease of the European rabbit is not the whole story. So let me dive a little bit deeper. So first off, mixomavirus is still and was first a virus of a different. rabbit species entirely, many different rabbit species, specifically the Sylvie Lagos species,

rabbits, endemic to South and North America. And in the Americas, in these species of rabbits, mixoma virus causes an entirely different disease, if you can even call it a disease, really. In American rabbits of the genus Sylvie Lagas, mixoma virus causes a single skin lump, a single mixoma and that's it that's it that's what it causes at the site of inoculation you get one big cutaneous lump and that's it so right off the bat here this virus is getting interesting because we see this huge variation in disease between host species in terms of the pathogenicity of this same virus so that's the first part of this story but number two is what I know you're going to talk a lot more about Aaron in the history section. But that is that mixoma virus's virulence in the European

rabbit dramatically changed over time. So this incredibly lethal version is not the only one which exists. And okay, I don't want to step on your toes too much because I think that hearing this story in its entirety for the first time for most of our listeners is going to be so good. So at this point let me ask you, Aaron, do you have any other questions about the transmission or details that you want to know about the path of physiology of this virus? Yes. Okay. Okay. So in the European rabbit and these American rabbits, does the virus sort of enter in the same way and go through its normal replication cycle and move to the different, you know, parts of the skin or ears or whatever, the body to replicate and cause lesions in the same way over the same time period. Where do the

differences start to jump in? Great question. Okay, so this mixoma virus, when it gets inoculated under the skin, either from a mosquito probe or a little flea mouth or a needle in a lab, the virus first infects the rabbit's skin cells, their epidermal cells or their dermal cells. and it quickly rises to pretty high titers in those skin cells, in those lumps that appear. And then, in addition to infecting the epidermal and dermal cells, this virus will go on to infect dendritic cells, which I think we've touched on a number of times on this podcast, but these are white blood cells that hang out in our skin, and from there spread to our lymphatic system, and their goal is to present to other white blood cells, these viral particles, so that we can

start to mount an immune response. But what happens with mixoma virus is it begins to replicate in these dendritic cells. And then when these dendritic cells spread to our lymph nodes or our bone marrow and our spleen, this virus is able to continue to replicate and infect other white blood cells. So this virus ends up being at very high concentrations in these skin lesions when they appear. And importantly, rabbits are not infectious until these skin lesions appear. But they also then have virus that spreads throughout their body, throughout their lymphatic system, and is able to infect a number of different organs and potentially reach relatively high loads there as well. Now, to answer your question, Aaron, what's the difference between these different presentations? The less virulent forms

of mixoma virus and other similar laparoxypox viruses that are very closely related, some of which have been used to make vaccines against mixoma virus. One thing that they do differently is they're not as good at, or in some cases they can't at all infect those white blood cells. So what they cause is just a localized cutaneous infection, causing a localized cutaneous skin, findings, but not causing systemic disease. Okay. Gotcha. And that seems to really make one big difference. So the virulence we know is at least in part related to how well this virus spreads beyond the epidermis and dermis and how well it invades and replicates within the lymphatic system and

becomes a widespread infection. Gotcha. Okay. So then that kind of leads me into my next question, which is about immunity. So as we'll talk about later on in this episode, rabbits, the European rabbits that were exposed to maximatosis showed genetic resistance in later generations. And so they were able to be resistant to this virus separate from the virus's decreased virulence. That's a whole other part of the story, whatever.

Yeah, yeah. Basically, these rabbits were able to resist getting infected. Yeah. Is the mechanism of resistance the same in the European rabbit as this sort of, like, does it lead to the same reduced disease presence as we see in the American rabbits? Great question, Aaron. So the other part of the pathophysiology of this virus is that mixoma virus, mizomoviruses, all of the different strains, have a whole bunch, like more than I could possibly list in this podcast, of proteins that regulate the host immune system in a way that facilitates infection. So they have these proteins that, for example, inhibit pro apoptotic molecules.

What that means apoptosis is programmed cell death. That's one of the ways that animals, immune systems have of targeting and fighting off viruses by identifying and killing virally infected cells, right? Well, myxoma virus has a whole bunch of proteins that it creates specifically to prevent that process from happening in a number of different ways. They also have other proteins that help to interfere with the coordination and recruitment of leukocytes of white blood cells, basically down-regulating that white blood cell response to infections. They have other proteins that block the presentation of antigens by those, for example, dendritic cells and other antigen presenting cells, so that they block these rabbits' ability

to make antibodies or even recognize the viral antigens. So mixoma virus has a whole host of different mechanisms that affect a rabbit's immune response to infection that are really important in how much that rabbit is going to be able to resist or be susceptible to severe infection. So to answer your question, Erin, this, it seems like a lot of these specific proteins and mechanisms that the mixoma virus has evolved in the American rabbits and are kind of perfectly suited in those rabbits to reduce the immune response to a degree that allows for. the establishment of an infection but does not impair the rabbit's ability to like survive and thrive, but also allows the establishment of an infection that's actually infectious, right, that has high enough titers in the skin so that this virus can be transmitted. Okay, so it's like being able to tolerate and coexist.

Exactly. With, okay. Yeah. And so it's thought that then when those same kind of, proteins were introduced to the European rabbit, like that is what allowed for this establishment of a very severe infection because of the difference in their immune response and how these proteins interacted with that immune response. And so, yes, that's one of the things that tends to change over time as rabbits evolve resistance. It's really interesting.

I love it. I love it so much. I can't, like I get so excited. I think this, I swear this is my last one, but I was just thinking about it. So in these rabbits that are resistant in some way to macsoma virus, whether it's like the American rabbits that, you know, just have the skin lesions, et cetera, how long does the virus persist in those hosts? Oh, that's such a good question. And it's a really important part of the story as well. I don't know is the short answer to it. it depends a lot on what species you're talking about and also what strain of the virus you're talking about. But it does tend to be the case that, for example, in American rabbits, they can have these lesions that persist for a really long time. These cutaneous lesions can potentially persist for weeks, if not months. But again, they don't cause any systemic illness. In more resistant European rabbit populations or with less virulent virus strains, you can sometimes just see a

prolonged illness where it lasts maybe 15, 20, 30 days instead of like 8 to 12 days. So it is variable between species and between strains of virus. But it is an important part of the story. Yeah. Yeah. So yeah, that's, I mean, that's myxomavirus. Aaron? Interesting. I think there's more to the story. I mean, there's a lot more to the story. So can you tell us the story? I will. If I think of more questions along the way, I'm going to ask you. Oh, good. Sounds great. Okay. Let me, let's take a break and then we'll dive into the history of this virus and the European rabbit in Australia. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief.

It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments.

It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keef's. Just visit o'Keef's company.com slash this podcast and code this podcast at checkout. Why have I asked my electrician I found on Angie.com to bury my pet hamster nibbles in our yard for me?

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Bottom line, Xfinity is smart and reliable. You deserve the peace of mind of having Wi-Fi that's got your back. Xfinity. Imagine that. The story of rabbits in Australia, not just their arrival and spread, but also myxoma virus and then later attempts at biocontrol, It might be one of my favorite topics that we've ever covered on this podcast ever. Yeah. I mean, we've been talking about doing this and I've been wanting to do it for a very long time.

So I am really excited. I am too because, and it's like I said earlier on, this is such an incredible story because it covers so many different themes, right? Like you could learn about it in a veterinary class. You could learn about it in ecology class, an evolution class, a virology class, an economics class, a pest management class, history class, like so many different, there are so many different angles to this, but I think it's also really fascinating when you put them all together and consider just the full picture of this story. So yeah, it's about, you know,

not just how life finds a way. It also makes us think about why we choose to use the words invasive or pests to describe one species but not another and how those labels or the things defining those labels, how they shift over time. I could honestly go on and on about how excited I am and all the lessons that we're going to learn from the story, but like maybe I should just get to the story itself and then we can, you know, discuss the lessons as we go. Yeah. Okay, so the long and short of it is that rabbits were introduced to Australia. They bred like crazy, destroyed heaps of vegetation, and eventually the mixoma virus was introduced as a method of controlling rabbit populations. All right. So that's the short version. That's the short version. Let's go to

the long version. To do that, we have to go to 1788. This is where the story really begins. because that year, the first fleet brought the first European settlers to Australia, along with food, tools, agricultural equipment, seeds, alcohol, medical supplies, and a few rabbits. A few, just a few. Just a few. And these are not the rabbits that we need to worry about. There's no record specifically describing what happened to these first fleet rabbits, but they were likely domesticated rabbits.

and if there were any attempts to introduce them into the wild, they probably weren't successful. And the same could be said, more or less, for the domesticated rabbits that were brought to Australia in the decades after the First Fleet's arrival. That is until 1859. That year, everything changed. A farmer by the name of Thomas Austin got it into his head that hunting wild rabbits on his farm would be really, super fun. Like not the lame domestic rabbits that were kept in hutches. Like those aren't, those aren't fun to hunt. You want the wild ones. And he wanted the wild ones from his homeland of England. So he had his brother, who was living in Liverpool, send over two dozen wild European

rabbits. It seems that only 13 rabbits survived the journey from what I gather. But when they got to Austin's farm near Geelong in South Victoria, they were let go. Free to breed so that the farm would be stocked with nice wild rabbits to hunt. Oh gosh. And since rabbits breed like rabbits, that's exactly what they did. So it's estimated that one female rabbit produces about seven litters a year with an average of four to six bunnies in each litter. So let's say between 30 to 40 per year, One rabbit. Whoa. One rabbit.

Whoa. And by the end of a breeding season, those kittens, because did you know that baby rabbits are actually called kittens? I learned that. And it's one of my favorite things that I learned while researching this episode. It cracks me up. I'm like, wait a second. My whole life. I know.

Not bunnies. Kittens. Kittens. It's not in any of the children's books. No. At least not the ones I read. Yeah. So these, but the kittens.

that were produced in the early in the breeding season by the end of that same breeding season were sexually mature and breeding themselves. Oh, no. Mm-hmm. So, yeah, a lot of rabbits. A lot of rabbits. Like from 13 to who knows within one year, right? And then you could just see the growth curve on that, right? Yeah. Exponench. Exponantch, for sure. And also the change in environment from England to Australia, Like, those are, you know, they're pretty different climates and environments. It didn't slow them down at all because actually the European rabbit is thought to have evolved in the Iberian Peninsula and southern France in a Mediterranean climate. Yeah.

Side note. Did you know that Spain or Hispania, the name may have come from the Phoenician word meaning island of rabbits? No, I did not. There's a lot of different proposed explanations for the etymology of Spain, but that's one of them. I love it. Anyway, so these rabbits were doing quite well on Austin's farm and off of it. By 1865, six years after those 13 rabbits arrived, six years, Austin wrote that he had killed 20,000 rabbits off his estate.

Oh, my God. And that 10,000 still remained. In the next year's hunt, so this is seven years after their arrival, he reported over 14,000 rabbits killed. killed. Oh my God. The next year, 1867, Prince Alfred, son of Queen Victoria, killed over 400 in a three-hour hunting session. Oh my. And it wasn't stopped because there were no more rabbits left. It was too hot. Uh-huh. Uh-huh. Mm-hmm. Four hundred and three hours. I'm sorry. I, okay, I have a lot of thoughts. I know. The scale of this is really kind of hard, I think, to comprehend.

Yeah. Yeah. And Austin, the farmer, definitely helped along the spread of the rabbits, or at least likely, by introducing them to new areas and other people coming in and being like, I want rabbits too. This is hunting is really fun. But honestly, the rabbits didn't need that much help. And it's not like anyone was actively trying to prevent their spread. Instead, the arrival of the rabbits was seen as something to be celebrated. I know. We can look back at that now and be completely horrified because we know how this story plays out and how so many other introduced species stories play out. But let's consider the historical context.

As we always do, on this podcast we'll kill you. When Thomas Austin imported and released those rabbits, it was during the period of large-scale colonialism that was taking place around the globe. from around the 1500s into the early 1900s. And during that time, it was a really common practice for colonizers to bring with them things that reminded them of home or things that they used to eat or farm, basically anything they thought would make their new life easier or more pleasant. Colonialism is how so many different species traveled to new places, both intentionally or unintentionally.

rats, cats, foxes, starlings, so many species of plants, pathogens, I mean, like everything, everything. And the worldview that was imposed on the places being colonized was the one commonly held by most European or American colonizers at the time, that plants and animals were put on this earth for humans to eat or to use for work or to simply enjoy. biodiversity and the interconnectedness of species in an ecosystem, these things weren't really considered by the colonizers or even known about. A species' importance was defined by how it could be used for humans, the benefit that it gave to humans, not its ecological role. Those concepts, like the interconnectedness of all the organisms in an ecosystem

and just how interdependent they were, those may have been held by some people, or at least like, recognized a little bit by some people and some cultures, but they were still decades away from being widespread. Ecology as a field of study didn't really even get started until the 1920s, and the notion that biodiversity was important was even further in the future. And even if someone did hold those views back then, they probably weren't in a position to argue against those who were in power, making these decisions. Because introductions of non-native species like the European rabbit to Australia, they weren't just done casually by a few plant or animal enthusiasts, they were encouraged sometimes

to the point of being included as a government directive. Yes. For instance, legislation from New Zealand in 1861 was passed, quote, to encourage the importation of these animals and birds not native to New Zealand, which would contribute to the pleasure and profit of the inhabitants when they became acclimatized and spread over the country in sufficient numbers. Oh my God. Oh, my God. It's giving me palpitations. I know. I know. I know. It just they, there just wasn't the knowledge of, yeah. It's so hard to hear that, though, to go back and be like, oh my God, you intentionally ruined the world. I mean, we've been doing it. it for so long. I was going to say so, so many stories. Like, yeah. Yeah. Yeah. And so all of this is just to say

that if Thomas Austin hadn't brought over the rabbits when he did, it was probably just a matter of time before somebody else did. Yeah. Yeah. Just as certain species were valued for their potential for profit or enjoyment by humans, others were seen as hurting humans or human interests. Pest species. And this term is still plenty in use today, typically in an agricultural context. And it's separate from terms used to describe a species origin, like native or non-native slash introduced, which refers to where a species evolved or the term invasive, which describes a species that's been introduced and is detrimental to the native species in an area. So a pest species can be native or invasive. And there are a lot more terms dealing with these concepts, but, I don't want to overwhelm with terminology and definitions, but this concept of pest species is entirely defined by the meaning to humans for the most part. And it has origins all the way back to the agricultural revolution 10 to 12,000 years ago when people began to interact more with the plants and animals that disrupted their crop yields or their livestock numbers. And that gave rise to

this term pest from the Latin pestis for plague. And people devised ways to deter those pest species, like scarecrow's, manual removal, fences, poisoning, hunting and trapping, introduction of animals to control them, etc. Some species may have been considered pests almost universally, or at least wherever they were found, like mosquitoes, but for many others, the label of a species as pest depended on who you asked. Yeah. For instance, wolves and sheep. If you're a sheep farmer, you may consider wolves to be a pest species because they sometimes eat your sheep. But for other people, sheep are the real pests, changing an ecosystem with their grazing,

reducing habitat for other species. Over time, the concept of pest species changed. It expanded to include things like pathogenic microorganisms and parasites and arthropods that carry disease. And it also shifted as our understanding of ecology and biodiversity grew. And so species that were once viewed as pests lost that label as their importance to an ecosystem was recognized. And others that were once highly valued earned the pest label and then some as they wreaked havoc on the landscape. Like rabbits in Australia.

Like rabbits in Australia. And the switch from valued animal to dangerous pest for rabbits in Australia was sudden and nearly complete. Wow. These guys are, we need them gone. In the first few years after their arrival in 1859, people were thrilled, like I said. Hunting them was forbidden for several months out of the year to try to protect their numbers. Oh, my, oh my. And one man was fined 10 pounds for killing a rabbit on someone's property.

Oh, my gosh. But within 10 years of their introduction, their rapid spread at hundreds of kilometers a year. and enormous population explosion was looked at in absolute horror. As the rabbit spread, they consumed any vegetation visible, whether it was grass or shrubs or the bark of a tree, leaving almost nothing left for the prized sheep that many people farmed, let alone the native animal species. Millions of acres in land were forfeited in the late 1800s because they had been rendered useless by rabbits. Wow. And remember that guy who was fined 10 pounds for killing a rabbit? Uh-huh.

A few years after that, his son was spending 5,000 pounds a year to try to control the rabbits on his land. Oh. That's so sad. Yeah. And there was also legislation that was introduced in the 1880s requiring all farmers to control the rabbit populations. And if they didn't, they would be fined. Wow. Yeah. As rabbits spread even into areas that people had said, you know, oh, there's no way they can survive here.

This surely is not suitable land for rabbits. People began to realize that physical barriers might be needed. Some stronger efforts might need to take place. In the early 1900s, construction began on a giant rabbit-proof fence in Western Australia. and when fence number one was completed in 1907, it was the longest continuous fence in the world. Wow. It was 18333 kilometers or 1139 miles. Wow.

Yeah. Over a thousand. It's a lot. And supposedly rabbit proof, huh? Uh-huh. Well, no, maybe not so much. Later it was, I think, named the emu fence, and it did seem to have some effect in other pest species, quote unquote, but rabbits not so much. When it was constructed, it seems that rabbits could be found on both sides of the fence.

And a fence that long, it would have been really difficult, if not impossible, to maintain effectively. Yeah. There were two other rabbit-proof fences that were constructed around the same time. and it brought the total length of fencing to over 3,200 kilometers or 2,000 miles. So a pretty substantial effort. But fences weren't the only thing that people were trying to use to control rabbit populations. Poisons, especially strychnine and arsenic, which would be two potential great topics for future episodes. Yep, they would be.

They were a popular choice, as was ripping, which was the term used for tearing up the large underground burrows or warrants that the rabbit we're living in. This is one of the only species it seems that creates these large family warrens or burrows, which is actually really important to the transmission of mixomatosis. Also predators were introduced like foxes and cats to other sometimes invasive species, but nothing seemed to put a dent in the rapid expansion of rabbits. So let's talk about some of the characteristics of these rabbits that made them so successful at establishing. Okay. And it's really a mixture of both rabbits themselves and the Australia they entered into in

1859. So first, I already mentioned what efficient breeders rabbits are off the charts. Yep. Second, many of the places in southern Australia they first moved to were similar in climate to the places they evolved. I mentioned that as well. Third, they can move surprisingly long distances, just individual rabbits, but also allowing for the spread. Fourth, when they were brought over, they left most of their pathogens and parasites behind,

and there didn't seem to be any in Australia that could affect them. So what we call parasite escape. It's always the case with invasive species. It often is, yep. And then there was also predator escape, which is something that happens also a lot with other invasive species. So for decades, many farmers had been poisoning dingoes and other native predators who were considered pests because of livestock at that time. And so rabbits entered into this low predator environment, and it also might have taken some time overall for predators to even

recognize the rabbits as potential prey. Number six, there were already lots of burrows dug by batongs, bilbies, and wombats. I'm sorry. What's a batong and what's bilby? I know what a wombat is. My words alone can't do it justice. They are adorable small mammals. You should look them up.

I was like, there's are new mammals I've never heard of. I feel like Australia has a lot of mammals I've never heard of. Oh my gosh. I love them. So we just took a break so that Aaron could look up batongs and bilbies. and we recommend that you do the same because they're adorable. They're adorable. Okay, getting back to it.

So the billbies and the batongs built these burrows. These burrows. And so then when the rabbits came in, they were like, oh, sweet, free real estate. We're just going to move right in. And that was that. And number seven, human mediated changes to the landscape, like clear cutting of trees and the promotion of pasture lands. he's also paved the way for rabbits. And there's just the fact that it was, like I already said, this attitude of, oh, we can't wait to have these rabbits.

Let's promote their growth. Anything that, you know, we want to have here to make our lives better is going to be great. Yeah. Yeah. And so all of these factors combined meant that by the time people recognized there might be a problem, it was already way too late. Yeah. I want to read another quote about rabbit population growth in Australia from the time. Quote, rabbits overran the town in search of water.

They ate the gardens and burrowed under the houses. Shopkeepers had to wire net their premises. The servants at the hotels brushed them off the steps. The inspector of stock hunted two or three from under his bed each morning. School children killed so many on the way to and from school that the mayor had to employ a with a cart to gather them up. What? It's like, it is still hard for me to imagine.

It is. It's unimaginable. I can't picture that many little bun buns. Mm-mm. Mm-mm. But also not everyone saw rabbits as this threatening menace. They were also seen as an opportunity. The profession of rabbiter sprung up when bonuses were introduced for rabbit scalps starting in the late 1800s, and rabbiters did pretty well into the 1900s, even after this bonus system was scrapped. In the first few decades of the 20th century, upwards of a million rabbits were killed each year and canned for food to be sent to soldiers fighting in World War I and World War II.

Although the rabbit industry certainly was raking in some money, the cost of lost farmland and sheep grazing areas, it vastly outweighed that some. And in the late 1800s, the governments of Australia and New Zealand, where rabbits had also been introduced, decided to search for a solution. On April 26, 1888, these governments got together to establish the Royal Commission of Inquiry into schemes for extermination of rabbits in Australasia. Oh, wow. AKA the Intercolonial Rabbit Commission. The goal of this commission was to, quote, make a full full, and diligent inquiry as to whether or not the introduction of contagious diseases amongst rabbits

for promoting their destruction will be accompanied by danger to human health or to animal life other than rabbits. Pretty interesting. Yeah. They offered a 25,000 pound award, which in 1998 in Australian dollars, because that's when the book I read was from, was about 2 million Australian dollars. So it's quite a big reward. Yeah.

Yeah, the Elmer Fudd reward. That's funny. Thank you. He sounds so surprised. I forgot about Elmer Fudd. So yeah, anyone who could come up with a successful and feasible strategy for the destruction of rabbits would get this money. Hundreds of people from all over the world wrote in with this. There are different suggestions on how to kill the rabbits.

One of these people was none other than Louis Pasteur. Actually, I did think I think I saw that. So, so exciting. And he suggested a chicken cholera virus. But no one, including Pasteur, took home the prize. He was really angry about it. He was like, my solution is the best. This is discrimination against the French because the people who were judging were Germans

and they have this competition. Well, it was like over the top, for sure. But also his chicken cholera wasn't that deadly to rabbits, didn't seem to be super transmissible, and it wasn't restricted to rabbits. So like he shouldn't have gotten the prize. No, it's not a great option. Sorry, Louis. But it was really fascinating to me to read about this introduction of this idea,

the concept of using an infectious disease as a method. of control, it seemed so early. Yeah. But actually, people have been trying to use other organisms to control pest species for a long time. It's mostly been through the introduction of predators like cats and mongooses, and after germ theory, some pathogens as well. And there are many potential benefits to biological control methods over traditional

methods of control. For instance, they can be highly specific to just the target species. species, unlike poisons. They are often the only practical means for control if the species is already established in a large area and over diverse habitat. They can be self-perpetuating, and the cost benefit is low, right? You just cook up some, incubate some virus and release it. And see what happens. And see what happens. Yeah. But there are also risks. So we now know that biological methods of control are rarely. effective. Or if they are, it isn't for very long. They are self-perpetuating, which means

difficult to control. You kind of just let them loose. And there are often unforeseen consequences, which can lead to ecological cascades that have enormous long-term impacts on an ecosystem. Yeah. So it's like while biological control methods can potentially solve problems, they can also create new ones. For example, mongooses. is like a classic example, right? Throughout the second half of the 1800s, they were introduced to many islands in the Caribbean as well as Hawaii to try to control rats in the sugar cane, which were also invasive. But instead, they just ate iguanas and ground nesting birds and snakes and caused enormous population declines and some extinctions. And that led to a lot of indirect effects and ecological cascades. Yep.

Yeah. Mm-hmm. I mean, you can just, there are so many examples of biomexamins. biological control gone wrong. Oh yeah. Look at all of Hawaii. Yeah. Any island at all pretty much is really susceptible to these types of ecological collapses caused by an introduced species. Yeah. Okay. But since this is the classic story of biocontrol gone mostly right, I would say, I think it's about time that we meet the mixoma virus in this part of the story. So the mixoma virus was first

observed in 1898 by an infectious disease researcher named Dr. Giuseppe Sanarelli in Uruguay. It's one of the very first viruses described, coming shortly after the word virus was used to describe the filterable transmissible agent causing tobacco mosaic disease, which is what we always learn is the first virus, right? Sanarelli had imported some lab rabbits from Brazil to run some experiments, and some of them became super sick with swollen eyes and ears and faces. And he decided to name this disease mixomatosis. Muxa from the Greek word for mucus and oma for tumor. Tumor mucus tumor. This disease seemed especially deadly to the European rabbits in the lab, but not the ones

native to South America. And for about 10 years after Sanarelli published his findings, there was pretty much just like silence on the mixomatosis front. But then interest picked up. Other researchers, of course, grew interested. And over time, we learned a lot more about the virus, the role of arthropod vectors in its transmission, the reservoirs of the virus in North and South America, how immunity worked, how specific its host range was,

and importantly, how lethal the virus was in some species, like the European rabbit, but not others. Yeah. One of the people who became interested in this rabbit disease was a Brazilian researcher named Dr. Honrique Aragau, who spent his career at the Oswaldo Cruz Institute. Think back to our Shagas episode. Yeah. Araigau had worked on identifying the reservoir of mxomavirus in South America and also the role of arthropod vectors. And he was so impressed with the virus's ability to cause disease that in 1918, he wrote to the Austroids.

government saying you should use this virus as a control strategy for your rabbit problem. Wow. Which by then the rabbit problem was like internationally famous. Yeah. His suggestion was considered and then dismissed. Hmm. Mostly on the grounds that not enough research had been done to determine whether it would be effective or whether the virus could be dangerous to humans or other animals. Okay.

But while it got the official no at first, the idea wasn't entirely dropped. especially since some people were just getting so desperate for anything to work. And so in 1927, a series of experiments were carried out to see how transmissible and how specific it was. Could this actually be something we could use? The results weren't encouraging. Basically, it didn't seem like it would spread among rabbits easily. And even if it did, it was likely to result in a situation where rabbits would evolve resistance or tolerance. and the virus would decrease in virulence.

And researchers still couldn't be sure that it wouldn't spread to the native animal species or humans and cause a huge catastrophe. All fair points, and the idea was shelved yet again. And that could have been the last time that we ever heard about mixomatosis, if Dr. Jean McNamara hadn't come across the idea totally independently from Dr. Erigal. Dr. McNamara was a pediatrician from Australia, who in 1933 was awarded a fellowship to study polio in New York.

While there, she visited the lab of Dr. Richard Schope, whose name may sound familiar from our HPV episode. Oh. He discovered the Shope papillomavirus that had given rise to the jackaloupe myth and was one of the first people to link viruses to causing cancer. Jackalopes, okay. Yeah. But at the time of McNamara's visit,

that Shope was working on a vaccine against mxomavirus using the immunologically related fibromavirus. He showed McNamara the rabbits that were infected with mixoma, and when she saw how lethal it was, she was like, this could be useful. So she wrote home to her family, quote, I had a lovely day out at Princeton, the branch of animal and plant pathology.

There is a man there. I would love to take home to work on our animal diseases. Shope is his name, and he has something which, kills rabbits, though he has not tried ours. I'm going to send some to Ivan to give him the chance to become famous by killing off the rabbits. I love that. And so she sent some samples of the mixomavirus. They were destroyed upon arrival because things had been ramped up a little bit more seriously at like, you know, let's not introduce species and potential pathogens. But

nevertheless, she persisted and eventually convinced the Australian government to set up some experiments, commissioning Dr. Charles Martin in Cambridge to examine the virus's potential. Martin's experiments showed more promise than the 1927 ones, but there was still a great deal of hesitation to introduce it to Australia, not just on the grounds that it might not work, but that if it did work, there might be unintended consequences. But just like last time, more field experiments. were set up, and just like last time, they weren't overwhelmingly successful, and maybe that really would have been the end of it. But the landscape, which was already drastically altered by

years of rabbit population growth, it had grown even more rabbit infested during World War II when so many people left to fight in the war and rabbit control on some of these farms, like slipped. There was no way you just didn't have the human power to control the rabbit population. And so by the end of the 1940s, people were desperate for something to reduce rabbit numbers. And McNamara was like, okay, I'm going to say it again, mixomatosis. The last field trials were wrong. They were done in the wrong place. There were no mosquitoes there.

You need to do it again. And it turns out that the fourth or the fifth or whatever time it was, I've lost count, this time was the charm. Oh, yeah. In 1950, field experiments were set up where rabbits in different areas were inoculated. with the virus and then let loose to bring it back to the borough and the rabbits living in there. The first year, results weren't too impressive and the researchers in charge, Francis Ratcliffe and Lionel Bull, Francis Ratcliffe, by the way, was the author of the second quote that we read in the intro. They nearly pulled the plug. But then reports of sick rabbits began to come in from

southeastern Australia in areas where the virus had been released. In some places, over 90% of the rabbits had died within a month of the virus showing up. Wow. Yeah. 90% in a month. In a month. It's, again, hard to imagine. So it seems that heavy rains had led to a big mosquito season. And the mosquitoes were able to pick up the slack where direct contact among the rabbits alone had failed. And around this time is when Dr. Frank Fenner, who's one of the authors of that, great book that I read about this, he joined the team as the virologist. And Fenner would go on to uncover so much about viral evolution and resistance and also played a major role in the eradication of smallpox in Australia. So he was kind of a big

name in microbiology out there. So everything seemed to be going great with the maczoma virus. People were celebrating over the corpses of millions of rabbits in anticipation of the return of vegetation. Wow. But then there was a development that almost brought the whole thing to a stop. An outbreak of encephalitis cases of unknown cause in humans appeared alongside the rise in mixomatosis and the rabbits, which made people terrified that like, okay, this virus that you introduced is now infecting and killing humans.

A few researchers working on the mixomavirus knew that it couldn't be the cause of this illness. And so to reassure the public, researchers, doctors Frank Fenner, McFarlane Burnett, and Clooney's Ross injected themselves with myxoma virus and publicized the outcome, which was nothing but a slight red spot near the site of injection. No encephalitis. What was causing the encephalitis? It was actually found to be a relative of the Japanese encephalitis virus. It was given the name Murray Valley Encephalitis Virus after where the outbreak took place. Okay. And it's transmitted by mosquitoes. Mosquitoes, which were so prevalent, which were also transmitting my somatosis. Oh my gosh, I love it. I mean, I don't love that people got

encephalitis. But like, what a story. Like all the pieces fall into place. Yeah. Oh my gosh. Yeah. 1951, though, was the first year to show real promise in mixomatosis as a control agent for rabbits. But even though things were looking good, the disease seemed to be like, largely restricted to areas along rivers and lakes. But the next year, it exploded far beyond that. And with, like you said, this estimated case fatality rate of 99.8 percent, it obliterated. Obliterated. Any rabbit population it came into contact with. Wow. And within a few years of the virus's release, Australia's rabbit population dropped from an estimated 600 million to 100 million. Wow. Yeah. And this drop in population was not, of course, consistent or equal across the entirety of the rabbit-infested areas due to differences in climate. And so like mosquitoes might not breed as well in more hot and arid regions, and so they didn't experience as much of a decline.

And also, despite how huge an impact the virus was having on the rabbits, researchers on the project knew that it was. just sort of the honeymoon phase. It was only a matter of time before resistance popped up and attenuation crept in. And they were expecting it to happen eventually, but it showed up a lot faster than they thought, like years and years faster. By 1952 and 1953, so two and three years after the virus was introduced, less deadly strains of the mixoma virus or attenuated. strains had been discovered in some of the wild rabbits two to three years after. Wow. And later research showed that attenuated strains had popped up independently all over the

continent during the 1950s. And so let's talk about the trend towards decreasing virulence. Why was it evolving to become less deadly? Well, if you're a virus that's transmitted by direct contact and you kill your host before your host can pass it on, you won't survive as the virus. The strains that will survive are those that are less deadly, where the host maybe stays alive a few days longer to infect a few more rabbits. And this, you know, with the fast rabbit reproduction cycle and how many there were,

this evolution happened on a much faster time scale than people expected. And for their part, the severe bottleneck and rabbits meant that genetic resistance would be selected for. Those were the ones that survived to reproduce and pass along resistance alleles. Genetic resistance in rabbits also showed up in the mid-1950s, also decades ahead of predictions, and some fascinating lessons were learned about host pathogen co-evolution. In terms of the virus, although the general trend was towards decreased virulence, a study examining trends in viral evolution across Australia and Europe where it had been released show that there were multiple different evolutionary pathways the virus had taken. Eventually, all of these mxomavirus strains

seemed to have evolved to be less deadly. So it converged on this phenotype of being less deadly. But if you looked at them genetically, they didn't show those same patterns of genetic alterations, right? They weren't constrained by evolution in that way. They did it in like a bunch of different ways. So they got to the end result, but they took a bunch of different paths to get there. It's so interesting. Yeah. And research in the 1990s showed that although in general, there had been a trend towards less deadly strains, there were some strains that seemed to have evolved way back to super high virulence. And those highly virulent strains had apparently been selected for because they could overcome the rabbit's resistance. They were the ones that were called.

causing lesions where the virus could spread, whereas the less virulent ones were just kind of existing in the rabbits and then petering out. Right. Because it was this interplay between this rapidly evolving virus and an animal with a very short generation time that was rapidly evolving resistance. It is, it's so interesting. And I think it really also makes us rethink. I feel like there's especially in COVID times been this assumption that all pathogens

evolved to be less deadly. They evolved to be benign. And that is absolutely not the case. It really is more about transmission. Yeah, exactly. Oh, they evolved to be optimally transmitted, which could vary depending on how something is transmitted and how their host reacts to it and how much resistance they have. Like, oh, my goodness, Erin. It's, there's, there's no hard and fast rule, which is what we love about ecology. I know. Okay. So all of the that is super fascinating, but there's also some really interesting tidbits from the rabbit side of things, too. Yes. First, a study published in 2019 showed that in rabbit populations that had been exposed to macomavirus across Australia, France, and the United Kingdom over the past 60 years, the same alleles in the rabbits had been selected for, and that most of the alleles were immunity-related genes.

Interesting. Yeah. And so the rabbits showed a common genetic basis for the evolution of resistance, but the virus did not. Oh my gosh. That's cool. Isn't that really fascinating? So there was existing genetic variation in all of these rabbit populations all around the world. Right.

And that certain alleles were the ones that were present in all of these populations from the beginning were the ones selected for. Yeah, that is interesting. Huh. Super cool. Yeah. And then there's one more thing. Okay. And so this is something called a sire effect.

And it was found about rabbit resistance in these mixomatosis rabbits. Okay. So essentially, when a doe, an unselected doe, female rabbit, mated with a buck that had recovered from mixamotosis, had been infected and then recovered, the kittens were more resistant than expected. The risk of death had been reduced by about 25%. But only in that direction. Like only an unselected dough and a selected, a resistant buck, but not the other way around. At least I didn't see. Like, I would assume that there would be some maternal antibodies passed in, but this is, the dough is unselected.

And then the buck had been exposed. And it's not just in the litter that was produced when the dough and that buck had mated, but also, future offspring. Like of that dough with other bucks? Yeah. So even if a dough later mates with a buck that was not immune, if she had previously mated with a recovered buck within seven months of his infection, those offspring are also partially immune. What?

I know. Okay. I'll post more papers about this. It's really fascinating. And it's probably something to do with epigenetics. It's got to be epigenetics. It doesn't seem the mechanism. is known. Yeah. That's, oh my God, that is really bizarre. It just shows, like, also, this is such

an incredible system to have studied because there's so much known about it. You can watch these things happen in real time. There's just the more you dig, the more you find, the more questions you have. Yeah, I have so many. Okay, so despite the increasing resistance in rabbits and decreasing virulence in the virus, rabbit populations continued to decline, or at least even out, throughout the 1960s. And part of that was due to the introduction of the European rabbit flee in 1966, which was even more successful as a mechanical vector than the mosquito. And it was also somewhat due to the reactivation of the virus in rabbits with lesions, which allowed it to spread to rabbits who were newly susceptible. And by the 1980s, rabbit populations were under pretty good

control in some places, not eliminated by any means, but at least more manageable, maybe. But in drier and hotter regions, where mosquitoes weren't as prevalent and the European flea didn't survive well, rabbits were still a huge problem. And so the Spanish rabbit flea, which was adapted to that type of drier and hotter environment was introduced. Also was decently successful. But the story of rabbits in Australia was not over, and let's be honest, it may never be. Rabbit populations had begun to recover despite all of these interventions, and by 1991, it was close to half of the pre-mixomotosis population.

Whoa. Yeah. The rabbit hemorrhagic disease virus, a chalisi virus, also incredibly specific to rabbits. It was explored as a possible rabbit control agent in the 1990s after first being discovered in China in 1984. And in 1995, it actually escaped into wild rabbit populations in Australia from an island where field studies were taking place. So it was like, whoopsie. Yeah. But it had, they would have been planned to be released anyway. It was just a little ahead of schedule. A little early. Yeah. And the rabbit hemorrhagic disease virus proved to

be pretty successful as a control agent, especially in those hotter, drier areas where control had previously been challenging. And there have been repeated introductions of that virus since. So I've presented the story of rabbits in Australia as one of a villain, rabbits, and a hero, the mixoma virus. But as always, it's way more nuanced than that. And those roles could easily be swapped in other places where rabbits aren't considered pests. It's true that these introduced rabbits did and continue to do tremendous damage to ecosystems in Australia. By reducing overall vegetation and destroying new plant growth, including trees, they have eliminated some plant species, such as acacia trees and some species of grass in some areas.

And the overall reduction in vegetation has also led to the erosion of topsoil, which has impacts on the establishment of new plants, drought tolerance, potential for windstorms and wildfires, further destruction of habitat. This destruction is also not equal across Australia. For instance, in arid range lands, where plants often have long lifespans and very slow growth periods, rabbits eat seedlings and destroy plants that were decades old. The recovery times for these areas is much, much longer than others, and it's unclear whether complete recovery is even possible. And while initially the concern was primarily for the impact of rabbits on sheep or other livestock, many other species suffered at this destruction of habitat.

Rabbits limited resources from many other herbivores and out-competed them, in some cases completely driving out native burrowing herbivores from rabbit-infested areas, like bilbies, betongs, common wombat, spectacled hare wallaby, Western gray kangaroo and southern hairy-nosed wombat. Oh my goodness. And then there are many social and cultural aspects of rabbit control. Some feel the introduction of mxomavirus and rabbit hemorrhagic disease virus is inhumane, and efforts have been made towards finding a better way to achieve reduced rabbit populations,

like maybe through sterility. And there are also many people whose livelihood relies on or is supplemented by hunting rabbits for meat or peltz, and there have been calls to prevent the introduction of rabbit hemorrhagic disease. virus in some areas where rabbits are used for this purpose. These aspects have led to questions of how to weigh the role of the rabbit as a resource against its role as an environmental pest, which is a conflict that comes up often in questions of conservation. At this point, the war on rabbits in Australia has been going on for nearly 160 years. These introduced rabbits now occupy 70% of the continent, impact over 300 native plant and animal species, and cost an estimated

$200 million Australian dollars every year in lost production. Wow. Mixomatosis has been used as a control agent for rabbits in several other countries, and its story, as well as that of invasive rabbits, is likely far from over. But let's talk more about where we stand today with mixomatosis. What are those other rabbit populations impacted? Should we be worried? What's going on? Let's get into all of that after a quick break.

So mxomavirus today. Like you said, Aaron, it is not only a story of Australia. Mxoma virus was also introduced in France to control rabbit populations in France. And from there, it spread across Europe and into the United States. the UK. So mixoma virus is now found pretty well distributed around the world. It's endemic, of course, to North and South America, but it's also found across Europe, into the UK, and of course in Australia. And at this point, in much of the world where mixoma virus has been introduced, it has sort of established itself as an endemic pathogen now. It causes occasional epizotics, and primarily it is

these medium virulence strains that tend to predominate. So as it turns out, as this virulence kind of decreased, it was also found that when strains became really mild, where they caused very little disease and rabbits could recover really quickly, they only had transmissible tithers for a very short period of time. So it wasn't very infectious. And like you talked about a lot, Aaron, when rabbits died very quickly from infection, they were also really poor sources of infection, which in the case of mxoma virus isn't very surprising since something like a mosquito or a flea doesn't tend to feed from dead things. And rabbits don't hang out with their dead friends' bodies for very long. So both these highly virulent strains that wipe out rabbits

very quickly and these very mild strains where rabbits survive infection and recover, both of those tend to be poor sources of virus for transmission. And so it's these medium virulence strains, often called like 3A or 4. There's like a grading skill. So it's these grade 3 and 4 strains that tend to predominate. But at the same time, more virulent strains, like you mentioned, Aaron, in some populations where rabbits have developed a lot of resistance or evolved a lot of resistance, these more virulent strains still exist.

And so in different areas geographically, all of these different types of strains can actually co-exist, which is so fascinating. And if you think about it on an even larger scale, like the large scale evolution and ecology of this virus, it's not just the intrinsic virulence of the virus and the resistance of the rabbits. It's also larger scale things like weather.

Right? Turns out that cold weather increases effective virulence and warmer temperatures make it easier for rabbits to survive infection. Who knew? It's just so many variables. So many things. Nutritional status of the little bun buns. Whether they have any co-infections or other parasites that they're dealing with. Predator abundance. Because especially in the wild, predators are going to tend to remove sick rabbits that when you're looking at experimental trials, those rabbits might have. have survived for longer. It depends on seasonal influences. There are so many things that contribute to this continually evolving story of the co-evolution of mixoma virus and rabbits. It's so true. It really excites like the little ecology part of my brain where I'm like, but what about this? But what about that? How do you put this into a model? And then I'm like, no, I don't want to do any more modeling no more. Don't worry. Lots of people are doing the modeling, Aaron. We just get to read about it. Thank goodness. Thank goodness that people are doing the models.

But I think this topic, almost more than any other one we've covered, just was such a perfect example of how this is truly a snapshot. This is constantly evolving. All of the moving parts of this are constantly evolving. What's climate change going to do to the areas where, you know, are things going get hotter and dryer and there are going to be no more mosquitoes at all and the Spanish flea and the Spanish rabbit fleet can't survive? Like what's going to happen? Right. I know. And it does seem, you asked earlier on, Aaron, like how many other species of rabbits and hairs are we talking about here? And I don't know exactly, but I do know that there are more and more case reports and studies showing that, for example, the Iberian hair has now been found to be

infected with mixomatosis and have outbreaks that have caused deaths of hundreds of Iberian hairs, which are a totally different species in the Iberian Peninsula. And so, like, how much more could this spread? We don't know yet. Yeah. Right? How do we try and keep it under control? There are vaccines, which is great.

It seems from what I could tell, there's like two different groups of, vaccines that exist. Both of them are live attenuated vaccines, so live virus that are grown in a lab to be, not as virulent. One of them comes actually from the Shope fibroma virus, which again is that related virus that doesn't cause severe disease, just causes like a one big fibroma. And it kind of tends to cause some cross-protection against mxoma virus. Think cowpox inoculation and smallpox protection. Same idea, right? And then there are also a live attenuated vaccines that are made from various strains of the mxoma virus. These tend to produce a stronger and longer lasting immune response, but because they're from mxoma virus can also have the potential for mild disease. So from what I

could gather, in settings where you're raising a lot of rabbits, whether it's for, you know, domestic rabbits or for pelts or whatever it is, these two vaccines are often used in combination. from what I can tell. So like one dose of the chope fibromavirus and then a few months later, the mxomavirus so that you have really good protection. And the last thing that I want to just briefly mention because, first of all, this blew my mind. And I think it's incredibly cool. But also I'm mentioning it because inevitably people will ask, like, how does this relate to my life in specific as a human being who maybe doesn't care that much about rabbits. Fair enough.

Let me tell you, because this is incredible. So remember that little tiny spoiler I dropped at the top, that mixomavirus can replicate in a wide variety of cells in vitro and is very adept at replicating in human cancer cells? Mm-hmm. Well, turns out there's a lot of research into using mizoma virus as a cancer-fighting viral infection, essentially, something that could potentially be used in combination with chemotherapy

to treat various cancers. That is fascinating. Fascinating, Erin. Where are we in that research? Very early stages. Okay. There's also work being done to investigate mxomavirus as a treatment for chronic rejection of things like organ transplants and other diseases that have like a chronic

vascular inflammatory component because of all of its immunosuppressive properties. Oh. Oh, that's interesting. It's kind of like the way there's been research into human parasite infections. Yes, exactly. As like immunosuppressants. Yeah. So very early stages, actually the paper that I found that went into this was actually

kind of old at this point and I didn't find anything like more up to date. But we'll post it and you all can do your own research because I think it's really like a cool future direction. See, it's like one more lesson. One person's pest is another person's pet or potential cancer-curing microbe. Exactly. I love it. And that is mixomatosis. What a journey.

Seriously. I think this has just been so. interesting. It really has been. And do you know what else is so interesting that I feel like we only talked about just a little bit in this episode? What? The rabbit hemorrhagic disease virus. The rabbit hemorrhagic disease virus. We barely even got into it. It's true. We barely did. And if you're kind of bummed that we didn't really talk about it as much as you wanted us to maybe, you're in luck. Because next week, you can hear all about it. when we interviewed Dr. Robin Hall, who is a veterinary virologist, what a cool title, at CSIRO,

which is the Commonwealth Scientific and Industrial Research Organization in Australia. It's going to be so awesome. I am so excited about it. Yeah, me too. Okay, but for now, sources? Sources. I mentioned the book Biological Control of Ferdtent Pests earlier by Fenneran Fantini, and I also watched a couple of really fascinating YouTube videos on this.

One is called 160-year battle against one of Australia's worst invasives, another is called The Rabbit in Australia. And I will post links to those, as well as to a bunch of papers also that I read. I have a number of papers. Two of my favorites, just about the mxoma virus itself, were both by Peter Kerr, one from 2012, one from 2015. I will post both of those. And then that paper on, it was titled The Current Status and Future Directions of Muxoma Virus,

a master in immune evasion. That was the 2011 paper that really detailed kind of the future possible directions of mixoma virus that I thought was so interesting. We will post the sources from this episode and all of our episodes on our website, this podcast will kill you.com. We will. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to exactly right media.

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