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 paddocks stink with the dead ones.
Immediately prior to the liberation of Mixamatosis, a combination of circumstances had led to the build up 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 groundcover. 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 very clear before and after quotes. Yeah, those 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. Make Sematosis. Make Sematosis the Radiohead song. So we're gonna talk in this episode all about Tom Yorke and what inspired him to write the song mix and Metosis.
I have no idea what you're talking about.
Aaron Okay. Miximatosis 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 uh 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 is always the place. Hi, I'm erin Welsh.
And I'm Aaron Aman Upnike.
And this is this 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 mix and metosis. 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.
I gave it about a fifty five to forty five 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 gonna 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 quarantiny time.
It is What are we drinking this week?
We're drinking Bunny's Bug? Get it.
Bunny's Bug is a tasty little drink that has hop water.
Because 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 plusy Berta on our website, This podcast will kill You dot 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 transcript You can find our bookshop dot org affiliate account. You can find our good Reads 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.
Yeah, okay, well then should we you know, let's 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.
Fair warning, listeners, I am starting off this biology section kind of intentionally withholding.
Details for later dramatic effect. So let us begin.
Mixamatosis is a disease caused by the Mixoma 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 gonna ask I can't remember. Oops, But anyways, Yeah, this is a different genus of poxvirus. This is a lay poroxy pox virus, and smallpoxes an orthopox pox 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 poxvirus.
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 yeah, which are all called lagomorphs. I
learned so many new words researching this episode. But Mixima 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 mixoma virus in and letting it replicate.
Interesting.
Very And I'm throwing that little tidbit out there and then just gonna leave it to dangle and circle back to it at.
The very end of the episode.
Okay, I was, I was all poised to ask a question, but I can tell you're strange.
Okay, but today we're talking about rabbits. So this Mixoma virus causes the disease known as miximatosis in rabbits and hairs, and specifically, it causes the severe disease that we know of as miximatosis in the European rabbit Uricdologus cuniculus. If I'm saying that right.
Do you remember the Book'spinicula. 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 that it comes from.
That's very funny. I have not read those books. I'll put them on my Goodreads lists.
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 one o two to one oh three fahrenheit, which is thirty eight point nine to thirty nine point four c. 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 cutaneous popular 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 stirter, which is that like gasping inhale. And they generally die between eight to twelve days following infection.
And so that's like eight to twelve days after they first get exposed, so it's only like a period of four.
To yeah, four to six days, wow, four.
To eight days.
Yeah, it's a very very rapid course of disease. And mixamatosis, this disease classically has an almost unbelievably high mortality rate in the European rabbit ninety nine point eight to one hundred percent 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, we yeah, that we've covered so far.
Yeah. Yeah.
And so the virus, this mixoma virus is present in all of those goopy 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 epizootics or these outbreak scenarios. It does seem like vectors, especially mosquitoes, are pretty pivotal
in terms of large scale transmission. Without them, these outbreaks don't really spread or don't spread us quickly. Oh yeah, but the virus does not rely on mosquitos 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 born 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 tighters 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 rabbits?
Yeah?
I don't know exactly, but I do know that it seems like critical levels in the skin tissue are like ten to the seventh viral particles per gram of rabbit tissue, So that's like a little over ten million or so viral particles per gram, so really really high tighters 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 mix andmatosis 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, Mixoma virus is still and was first a virus of a different rabbit species, entirely many different rabbit species, specifically the Silvie Lagis 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 silvie lagis mixomavirus causes a single skin lump, a single mixoma and that's it.
That's it, that's what it causes.
At the sight 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 aarin in the history section, but that is that Mixoma virus is 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 Erin, 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 europe 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 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 mixamma 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 rabbits skin cells, their epidermal cells, or their dermal cells, and it quickly rises to pretty high tighters 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 mixomavirus 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 sentations the less virulent forms of maxoma virus and other similar laporoxypox viruses that are very closely related, some of which have been used to make vaccines against maxomavirus. 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
localized cutaneous skin findings, but not causing systemic disease. Okay, 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 mixematosis showed genetic resistance in later generations, and so they were able to be resistant to this virus separate, you know, from the virus's decreased virulence. That's a whole other part of the story or 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 questionnairein so the other part of the path of physiology of this virus is that mix omavirus mix oma viruses 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, while mixomavirus 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 anogens by those, for example, dendritic cells and other anigen presenting cells, so that they block these rabbits ability
to make antibodies or even recognize the viral antigens. So Maxoma 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 questionarin.
This, it seems like a lot of these specific proteins and mechanisms that the Maxoma 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 survive and thrive, but also allows the establishment of an infection that's actually infectious, right, that has high enough tighters 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.
Oh, 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 Maxima virus, whether it's like the American rabbits that you 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. And I think 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 fifteen twenty thirty days instead of like eight to twelve 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 an example virus Aaron interesting, It's I think there's more to the story.
I mean, there's a lot more to the story. So so can you can you tell us the story?
I will if I think of more questions along the way, I'm gonna 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. The story of rabbits in Australia, not just their arrival and spread, but also mix Oma 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 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 an 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 can consider just the full picture
of this story. So yeah, it's about, you know, not just how life finds a way it Also 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 mix Oma 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 seventeen eighty. 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.
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 eighteen fifty nine. That year
everything changed. A farmer by the name of Thomas Austen got it into his head that hunting wild rabbits on his farm would be real, the 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 thirteen 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 thirty to forty per year one rabbitsh 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. No, 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, so yeah, a lot of rabbits like from thirteen to who knows within one year, right, and then you could just see the growth curve on
that right. Yeah, exponentch exponentch for sure. And also the change and environment from England to Australia like those are you know, they're pretty different in climates and environments. It didn't 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 eighteen sixty five, six years after those thirteen rabbits arrived. Six years Austin wrote that he had killed twenty thousand rabbits off his estate, oh my god, and that ten thousand still remained in the next year's hunt. So this is seven years after their arrival.
He reported over fourteen thousand rabbits killed.
Oh my god.
The next year, eighteen sixty seven, Prince Alfred, son of Queen Victoria, killed over four hundred in a three hour hunting session. Oh my. And it wasn't stopped because there were no more rabbits left. It was too hot. Four hundred and three hours.
I'm sorry. Okay, I have a lot of thoughts.
I know, the scale of this is really kind of hard I think to comprehend. Yeah it 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.
Oh, 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 it. I'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 fifteen hundreds into the early nineteen hundreds, 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 two 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 nineteen twenties, and the notion that biodie diversity 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 were 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 eighteen sixty one 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 for so long.
But I was gonna say so so many stories like yeah, yeah, yeah, And so all of this is just to say that if Thomas Austen 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 disc vibes of 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 ten to twelve thousand 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 scarecrows, manual removal, fences, poisoning, hunting and trapping, introduction of animals to control them, et cetera. 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, So 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 carried 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.
Rabbits in Australia, and the switch from valued animal to dangerous pests 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 eighteen fifty nine, 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 ten pounds for killing a rabbit on someone's property.
Oh my gosh.
But within ten years of their introduction, their rapids spread at hundreds of kilometers a year, and enormous population explosion was looked on. 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 than native animal species. Millions of acres in land were forfeited in the late eighteen hundreds
because they had been rendered useless by rabbits. Wow. And remember that guy who was fined ten pounds for killing a rabbit. A few years after that, his son was spending five thousand pounds a year to try to control the rabbits on his land.
That's so sad.
Yeah. And there was also legislation that was introduced in the eighteen eighties 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 is surely is not suitable land for rabbits, people began to realize that physical barriers might be needed, some stronger efforts that might need to take place. In the early nineteen hundreds, construction began on a giant rabbit proof fence in Western Australia, and when fence number one was completed in nineteen oh seven, it was the longest continuous
fence in the world. Wow. It was eighteen one hundred and thirty three kilometers or eleven hundred and thirty nine 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 thirty two hundred kilometers or two thousand 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 warrens that the rabbits were 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 mix andmatosis. 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 rabbit. 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 eighteen fifty nine. So first I already mentioned what efficient breeders rabbits are off the charts. 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. Yet and then there was also predator escape, which is something that happens also a lot with other invasives 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, bilbi's and wombats that.
Sorry, what's a batongue?
And what's bill b 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 can't. I was like, these are new mammals I've never heard of.
There.
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 bilbie's and I recommend that you do the same because they're adorable. They're adorable.
Okay, getting back to it. So the bilbi's 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 is 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 wiren at 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 man with a cart to gather them up. Oh, 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 m m.
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 eighteen hundreds, and rabbits did pretty well into the nineteen hundreds. Even after this bonus system was scrapped, in the first few decades of the twentieth century, upwards of a million rabbits were killed each year and canned for food to be sent to soldiers fighting in
World War One and World War II. Okay, 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 eighteen hundreds, the governments of Australia and New Zealand, where rabbits had also been introduced,
decided to search for a solution. On April twenty sixth, eighteen eighty eight, 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 and diligent inquiry as to whether or not the introduction of contagious diseases amongst rabbits for promoting their destruction, will be accompanied by dangers to human health or to animal
life other than rabbits. Pretty interesting, yeah. They offered a twenty five thousand pounds award, which in nineteen ninety eight in Australian dollars because that's when the book I read was from was about two million Australian dollars, so that'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 their different suggestions on how to kill the rabbits. One of these people was none other than Louis Pasture.
Actually, I did think, I think I saw that.
So exciting, and he suggested at chicken colera virus, but no one, including Pasture, 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, oh, 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 you 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, 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.
Let's 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 unf foreseen 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. This is like a classic example. Right throughout the second half of the eighteen hundreds, 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 cause enormous population declines and some extinctions, and that led to a lot of indirect effects and ecological cascades. Yep, yeah, I mean you can just there are so many examples of 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 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 eighteen ninety eight by an infectious disease researcher named doctor
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 all which is what we always learn as the first virus.
Right.
Yeah. 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 miximatosis maxa, from the Greek word for mucus and oma for tumor, tumor mucus 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 ten years after Sanarelli published his findings, there was pretty much just like silence on the mixmatosis 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 doctor Hanrique Aragau, who spent his career at the Oswaldo Cruz Institute. Think back to our Shagas episode. Yeah, Aragao had worked unidentifying the reservoir of Maxoma virus 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 nineteen eighteen he wrote to the Australian 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, 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 nineteen twenty seven 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 miximatosis if doctor Gen McNamara hadn't come across the idea totally independently from doctor Ericau. Doctor McNamara was a pediatrician from Australia who in nineteen thirty three was awarded a fellowship to study polio in New York. While there, she visited the lab of doctor Richard Schope, whose name
may sound familiar from our HPV episode. He discovered the chop papolloma virus that had given rise to the jacalobe myth and was one of the first people to link viruses to causing cancer jacalobes. Okay, yeah, but at the time of McNamara's visit, Shope was working on a vaccine against maxoma virus using the immunologically related fibromavirus. He showed McNamara the rabbits that were infected with maxoma, and when she saw how lethal it was, she was like, uh,
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 her animal diseases. Shop 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 Maxoma virus. 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 gential pathogens. But nevertheless, she persisted and eventually convinced the Australian government to set up some experiments, commissioning doctor Charles Martin and Cambridge to
examine the virus' potential. Martin's experiments showed more promise than the nineteen twenty seven 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 rabbit control on some of these farms like slipped, like there was no way. You just didn't have the human power to control the rabbit populations. And so by the end of the nineteen forties people
were desperate for something to reduce rabbit numbers. And McNamara was like, Okay, I'm going to say it again, mix thematosis. 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 nineteen fifty, 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 burrow and the rabbits living in there. The first year results weren't too impressive, and the researchers in charge, Francis Ratcliffe and Lionel Bowl. 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 sick rabbits began to come in from southeastern Australia in areas where the virus had been released. In some places, over ninety percent of the rabbits had died within a month of the virus showing up.
Wow, yeah, 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 a direct contact among the rabbits alone had failed.
And around this time is when doctor 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 Maxoma 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 miximatosis 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 Maxoma virus knew that it couldn't be the cause of this illness, and so to reassure the public, researchers doctors Frank Venner, McFarlane, Burnett, and Clooney's Ross injected themselves with Maxoma virus and publicized the outcome, which was nothing but a slight red spot near the site of injection of 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, and it's transmitted by mosquito mosquitos which.
Were so prevalent, which we're also transmitting Magsimitata's Oh.
My gosh, I love it.
I don't love that people got encephalitis, but like.
All the pieces fall into place, yeah, oh my gosh. Yeah. Nineteen fifty one, though, was the first year to show real promise in mixamatosis as a control agent for rabbits. But even though things were looking good, the disease seemed to be largely restricted to two 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 ninety nine point eight 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 six hundred million to one hundred million.
Wow. Yeah.
And this drop in population was not, of course, you know, 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, an 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 nineteen fifty two and
nineteen fifty three. So two and three years after the virus was introduced, less deadly strains of the mix Oma 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 nineteen fifties. 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 with the fast rabbit reproduction cycle, and how many there were, this evolution happened on a much faster
timescale 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 and rabbits also showed up in the mid nineteen fifties, also decades ahead of predictions, and some fascinating lessons were learned about host pathogen coevolution
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 showed that there were multiple different evolutionary pathways the virus had taken. Eventually, all of these Maxoma virus 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.
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 nineteen nineties 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 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 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've to be benign, and that is absolutely not the case. It really is more about transmission.
Yeah, exactly, although 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, Yaren there's no hard and fast rule which is what we love about ecology. Okay, So all of 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 twenty nineteen showed that in rabbit populations that had been exposed to MaxMa virus across Australia, France, and the United Kingdom over the past sixty 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, and that certain alleles were the ones that were present in all of these populations from the beginning were the ones.
Gosh, 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 in about rabbit resistance in these in these miximatosis rabbits. Okay, so essentially when a dough an unselected dough female rabbit mated with a buck that had recovered from miximatosis, had been infected and then recovered, the kittens were more resistant than expected. The risk of death had been reduced by about twenty five percent.
But only in that direction, like only a selected 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, yeah, 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 in that buck had made it, 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 not even the mechanism is known.
Yeah, that's oh my god, that is really bizarre.
This 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 gos. 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 nineteen sixties, and part of that was due to the introduction of the European rabbit flee in nineteen sixty six, 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 nineteen eighties, 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 dryer 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 nineteen ninety one it was close to half of the pre mixematosis population.
Whoa yeah.
The rabbit hemorrhagic disease virus a kelisi virus, also incredibly specific to rabbits, was explored as a possible rabbit control agent in the nineteen nineties after first being discovered in China in nineteen eighty four, and in nineteen ninety five it actually escaped into wild rabbit populations in Australia from an island where field studies were taken place, so it was like whoopsie, yeah, but they would have been planned to be released anyway. It was just a little head
of schedule. 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 continued 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 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, and further destruction of habitat. This destruction is also not equal
across Australia. For instance, in arid rangelands, 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 for many other herbivores and out competed them, in some cases, completely driving out native burrowing herbivores from rabbit infested areas like bilbies, batongs, common wombats, spectacled hair 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 mixomavirus 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 pelts, 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
one hundred and sixty years. These introduced rabbits now occupy seventy percent of the continent, impact over three hundred native plant and animal species, and cost an estimated two hundred million Australian dollars every year in lost production. Wow. Miximatosis has been used as a control agent for rabbits in several other countries, and its story, as as well as that of invasive rabbits, is likely far from over. But let's talk more about where we stand today with maximatosis.
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 maxoma virus today, like you said, Aaron, it is not only a story of Australia Mixoma virus was also introduced in France to control rabbit populations in France, and from there it spread across Europe and into the UK, so Maxoma 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 Maxoma virus has been introduced, it
has sort of established itself as an endemic pathogen. Now it causes occasional episode 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 tighters for a very short period of time, so it wasn't very infectious, and like you talked about
a lot aarin, when rabbits died very quickly from infection, they were also really poor sources of infection, which in the case of Maxoma 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 friend's bodies for very long. So both these highly virulent strains that wipe out rabbits very quickly and these very very mild strains where rabbits survive infection and recover, both of those tend to be poor sources of virus transmission, and so it's these medium virulence strains often called like three A or four. There's like a grading scale, so it's these grade three and four 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 totures make it easier for rabbits to survive infection.
It's just so many, se 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 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 mixomavirus 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 here and we could just get to read about it.
Thank goodness, Thank goodness, other 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 our thing is going to get hotter and drier and there are going to be no more mosquitoes at all?
And the Spanish flea, the Spanish rabbit flea 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 hares 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 miximatosis and have outbreaks that have caused deaths of hundreds of Iberian hairs, which are a totally different species in the IBERIANSLA 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 Maxoma virus. Think cowpox inoculation and small prox protection, same idea, right, And then there are also a live attenuated vaccines that are made from various strains of the Maxoma virus. These tend to produce a stronger and longer lasting immune response, but because they're from Maxoma 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 shop fibromavirus and then a few months later the Maxoma virus 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 maxoma virus can replicate in a wide variety of cells in vitro and is very adept at replicating in inhuman cancer cells. Mm hm, Well, turns out there's a lot of research into using maxoma 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 maxoma virus 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 Exactlyssance, 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 y' 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 micro exactly exactly.
I love it, And that makes mix sematosis.
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 doctor 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 gonna 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 Vertebrant Pests earlier by Fener and Fantini, and I also watched a couple of really fascinating YouTube videos on this. One is called one hundred and sixty Year Battle against one of Australia's worst invasives, and 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 mixoma virus itself, were both by Peter Kerr, one from twenty twelve, one from twenty fifteen. I will post both of those, and then that paper on it was titled the Current Status and Future Directions of Mixsoma Virus, A Master in Immune Evasion. That was the twenty eleven 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 dot com.
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You filthy animals.
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