This Podcast Will Kill You - Special Episode: Rabbit Hemorrhagic Disease Virus

Episode Date: March 1, 2022

We ended our myxoma virus episode on a bit of a cliffhanger, briefly alluding to the emergence of another deadly rabbit virus on the global scene. In this follow-up bonus episode, we take a closer look at this recent arrival, rabbit hemorrhagic disease virus (RHDV), and what its rapid spread around the world has meant for both invasive European rabbits in Australia as well as native rabbit species around the world. Dr. Robyn Hall (@Virologica), veterinary virologist, epidemiologist, and Team Leader of the Rabbit Biocontrol Team at CSIRO in Australia, walks us through how this virus earned the nickname “bunny Ebola”, where it seems to be having the most impact, and what the sudden appearance of a new type of RHDV has taught us about viral evolution and ecological cascades. Then, once we fill up on RHDV facts, we talk favorite viruses, life as a veterinary virologist, and so much more! Tune in wherever you get your podcasts. And check out our website for links to where you can learn more about this fascinating and deadly virus. See omnystudio.com/listener for privacy information.

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Get started at redfin.com. Own the dream. Hi, I'm Aaron Welsh, and this is This Podcast Will Kill You. I'm back with another bonus episode in our mini series of bonus content that will be releasing over the next few months. In case this is the first bonus episode you're tuning into and you're wondering what the heck is going on, I'm using these episodes as an opportunity to explore more about whatever disease or topic we covered in our previous week's episode and also to get to chat with experts about their jobs, their hopes, their dreams, whatever comes to mind. If you've listened to the podcast before, you know that I'm kind of a relentless question asker. And so instead of just pestering Erin Updike with all the questions, I'm saving some for these episodes.

And so far, I've gotten to have some great conversations with people in very different careers, studying or working on very different problems. And this week, I am so excited to have yet another fun conversation and learn a whole lot more about another topic. So what am I going to be talking about today? This week really kind of picks up where we left off in our most recent. recent regular season episode, which covered a virus of rabbits called the mixoma virus. If you haven't listened to that episode yet, I would recommend checking it out before listening to this just because there's so much more to that story. But I'll give a quick

recap here. The mixoma virus is a type of pox virus that can cause severe disease in some species of rabbits, and it became internationally famous back in the 1950s when it was introduced to Australia as part of efforts to control the invasive European rabbit population. What had started out as a handful of European rabbits, introduced to Australia in 1859, had within a few decades grown to an absolute ecological and agricultural menace. Entire ecosystems were disrupted. Native animals experienced tremendous population declines. Many plant species were driven locally or regionally extinct, and huge tracks of land could no longer be used for agriculture. The introduction of the mixoma virus did help

to drive down or stabilize rabbit populations, but over generations, the virus lost a bit of its impact, as both rabbit and mixoma virus adapted to one another. The deadly virus was no longer as deadly as it once was, and the rabbit was no longer as susceptible as it used to be. So when another lethal virus of European rabbits was identified in the 1980s, the rabbit hemorrhagic disease virus, or RHDV, it was explored as another possible form of biocontrol for rabbits in Australia, and RHDV was introduced in the mid-1990s, again helping to keep rabbit populations under control. But the story of rabbits in Australia doesn't end there, and neither does the story of the rabbit hemorrhagic disease virus. In 2010, a new type of the virus,

was discovered in France, the aptly named rabbit hemorrhagic disease virus type 2, and this one doesn't seem limited to just European rabbit populations. Since its discovery, RHDV2 has spread around the world and has led to concerns for domestic pet rabbits, as well as the wild rabbits and hares that are susceptible, especially in places which have already seen damaging ecological cascades from RHDV1. So what I really wanted to explore in this bonus episode was these two viruses, RHDV1 and RHDV2.

Where did they come from? What effects have they had on rabbit populations? Are they following the same evolutionary patterns as mxomavirus? How worried should we be? And to help me answer these questions and so many more is Dr. Robin Hall, veterinary virologist and team leader for the rabbit biocontrol team at CSIRO, the Commonwealth Scientific and Industrial Research Organization, which is a government agency in Australia. I am super excited to jump into this interview, so I'll just take a quick break here, and then we'll get started.

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com slash this podcast. Hi, I'm Robin Hall. I'm a veterinary virologist and epidemiologist at the Commonwealth Scientific and Industrial Research Organization or CSIRO based in Canberra, Australia. Team leader for the rabbit biocontrol team here. And I have a special interest in host pathogen interactions, management of invasive species, and viral evolution. Awesome.

Thank you so much for taking. the time to chat with me today. I am thrilled. Thanks for the opportunity. It's, yeah, really exciting for me. So in our episode on mixomatosis, Aaron and I talked a lot about the long history of European rabbits in Australia and how this invasive species has been incredibly damaging, both ecologically and economically. I was wondering if you could bring us up to speed on the current situation with rabbits in Australia. Like, what do we know about the impact that there's still having and where does their continued presence seem to be the most problematic? You know, back in the 1950s, rabbits were at massive plague proportions throughout Australia.

And then with the introduction of myxomavirus, it was incredibly effective in reducing population numbers. But of course, populations begin to recover over time. And so in the mid-90s, HDV or rabbit hemorrhagic disease virus was released. Again, with massive declines in rabbit populations, but over time, you know, biocontrols are not a silver bullet, and once more rabbit populations began to increase. And so that led to in 2017 the release of a new variant of RHDV, which we call K5 in Australia. And again, we're still seeing the impacts from both the K5 release

and the arrival of this new virus RHDV2 in Australia, which was not deliberately released, but has spread here as it has globally. And so currently rabbit populations are relatively suppressed to comparatively to what they have been in the past. But we do still see considerable impacts. And these fluctuate on a bit of a boom and bust cycle. You know, when conditions are good, the populations will breed very rapidly and increase in size. And if we go into a period of drought, then populations can decline again.

So the impacts we see are really most obvious in environmentally sensitive areas. So particularly in the arid and semi-arid zones, where rabbits compete with native species for food and shelter, and they eat native plants that are already finding it difficult to grow in these arid conditions. And then, of course, in agricultural industries as well, where they impact crops through grazing, they damage the soil, they compete with livestock for food. And again, particularly in drought conditions, those impacts are more severe. And they also, rabbits also have some perhaps less considered impact. So things like they impact our Indigenous cultural heritage sites by damaging these artefacts and sacred sites and things. And even the impact of reducing the vegetation,

I mean, that then exposes more soil and the soil can then blow into the fleece of sheep, which reduces fleece quality. So there's this really sort of lead-on effects and they really have dramatic impacts that are quite wide-ranging and both direct and indirect. Our last episode focused on one of the most impactful tools for rabbit control in Australia, of course the maxoma virus.

And we also briefly mentioned the rabbit hemorrhagic disease virus, which I cannot wait to ask you more about. But these two biocontrol agents, they're not the only tools used to try to suppress rabbit populations. So can you talk about the other methods that are used? When we talk about a control tool, you really want something that's going to be effective, relatively cheap or easy to distribute. And viruses are really the only thing that we have that are self-disseminating,

that work on a landscape scale with the existing technologies. However, certainly at local levels, there are a lot of other tools that can be used. So particularly poisons are used quite heavily. So Pindone, but also 1080. So Pindone is an anticoagulant. So it's like rat bait sort of. And 1080 is a metabolic toxin. We also focus a lot on habitat removal.

So destroying the warrants or if they're harboring in shrubs, removing the shrubbery where possible. Shooting and trapping can be employed on a local level. Exclusion fencing has been implied. So where you put up fences that keep the rabbits out. But again, you have to dig it down and put it up relatively high. and then war infumigation where you introduce like a gas into the warren to kill them. So all of those other methods, they are very effective at local levels. But as you can imagine, they're quite labour intensive.

And certainly, you know, we can't use them across the landscape scale of Australia. So now I am so excited because I get to ask about rabbit hemorrhagic disease virus. I read that this is a callisi virus. What does that mean? Like, are there other types of calici viruses? Yep. I'm very happy to talk about RHDB as well. So, yeah, RHDV is a calisivirus.

These are small RNA viruses. So like the coronavirus is an RNA virus as well. It has an RNA genome. But coronaviruses have like 30,000 letters in their genetic code, whereas these colisi virus has have like seven and a half thousand letters. So we call them small RNA viruses. The shell or the caps. that the genome is packaged into is non-enveloped.

And so that means that they're incredibly environmentally resistant. So like I think again, we hopefully all know now with coronavirus that, you know, it doesn't survive particularly long on surfaces and it does use droplets and things like that and protected in that moist droplet environment. Whereas calisiviruses, because they're non-enveloped, they can survive on surfaces or in soil or something for months. Calesi viruses are pretty common and probably occur in most, if not all vertebrate species, although we are really only starting to look at the virus sphere more broadly.

But some that you may have heard of would include like human norovirus, feline calisivirus. So it's something that we vaccinate our pet cats for. And then there are calici viruses of, you know, cows, mice, pigs, chickens, Atlantic salmon. So, yeah, it's a big family, and the rabbit and hair ones, they're there as well. How are these viruses transmitted? Or maybe in particular, how is RHDV transmitted? A lot of the calisiviruses are transmitted by the fecal oral root. So, you know, you ingest them either from a contaminated surface or something like that. And then they're replicating the body.

They're passed out in the feces and then contaminate their environment. And so RHHHGELDF. broadly follows that process. However, because again, this environmental stability, RHDV can also get picked up mechanically by insects, so particularly carrion flies. The typical life cycle for an RHDV virus is it's ingested somehow. So either, you know, the grass is contaminated, the rabbit eats it, or the rabbit sniffs a dead rabbit and gets it in that way. Or a blowfly comes and lands on like the eyelids of a healthy rabbit and deposits some virus there. And then the rabbit grooms itself and eats it the virus that way.

The virus then goes into the gut, enters the animals systemically and causes this major infection that we can talk about in a second. And then the rabbit dies, typically within 46 to 72 hours post-infection. So this thing is incredibly, incredibly fast. And then the carcass starts to break down and contaminates the environment. and the flies can come in and pick it up and move it between populations. What's going on at the pathophysiological level? And like what's a typical course of infection?

What does that look like? So from the outside, you frequently don't see clinical signs, which I guess is great from a biocontrol perspective because the welfare is actually, I mean, anything that kills something, you don't want to say welfare is good, but it certainly has less impact on the animal than something like, say, mxoma virus. So many pet owners, you know, we often hear that, oh, it was fine, it was eating the night before I came in in the morning, it was dead. And so you often find them still with food in their mouth. And so it does happen very quickly. And frequently, you don't see any clinical

signs in the rabbit unless you're sort of taking temperatures every few hours or something. At the pathophysiological level, basically what happens is the virus goes in. It targets the liver. so it starts to replicate in the liver and it causes this massive hepatitis that all the liver cells start to bust open and the liver just pretty much disintegrates, I guess. And so that leads to, you know, a cytokine storm as such. And so you get this massive systemic inflammatory response syndrome, disseminated intravascular coagulation and, you know, circulatory shock and death. And so that sounds all very awful and it is, I guess.

But it's a fairly typical hemorrhagic fever virus. So, you know, some people have referred to it as bunny Ebola and things like that. But basically the virus goes in, causes a lot of damage to the internal organs, sets up this massive inflammatory response, and then the body's just overwhelmed. And so is that course of infection, is that fairly consistent across individuals within a population or within a species? And how variable is that across species as well? So RHDV is incredibly species specific.

So there's a couple of different variants of RHDV. RHDV1 was like the original RHDV that was first reported in sort of the 1980s. And that RHDV1 only affect European rabbits. So there's no definitive evidence that it can replicate in any other species. Then in 2010, a new variant called RHDV2 emerged. And what we saw with RHGB2 is that it can also infect other lagomorph species. So hairs or jack rabbits, the lepers species, and then also the cotton tails or the silver-largas species.

But still people are looking and have looked and there's no evidence of any disease outside of those legamorph species. Within a species or within individuals, within naive individuals, certainly the disease course is pretty typical. see a case fatality rate, you know, upwards of 95%, 99%. So it's, it is very, very consistent. In animals that have some degree of preexisting immunity, then the infection can look quite different. So you may get prolonged infections. They may get a subclinical hepatitis with jaundice and things like that. And then secondary liver disease. But again, that sort of depends on the

level of immunity. But in naive individuals, it's very, very consistent with an extraordinarily high case fatality, right? Where did these viruses come from? What do we know about the origins either of RHDV-1 or RHDV-2? Yeah, I mean, where do viruses come from? That's a big question, isn't it? It is. So certainly, you know, when RHDV-1 emerged in the 1980s, it was reported in Angora rabbits in China. These rabbits are being bred for fur, and they just observe these mass mortality events. So it was pretty clear that something was going on and they identified this virus and later it was found to be a calisi virus and things like that. So we're fairly confident that, you know, it wasn't around beforehand or for a long period of time beforehand because

we would have seen these math mortality events. A couple of hypotheses as to how that virus emerged, it could have either been a species jump. So the same thing as mixoma virus, you know, it's completely subclinical in its natural reservoir host, but when it transmits to European rabbits, it becomes highly virulent in that species. And so that is one hypothesis. Or it could be recombination. So these viruses recombined. So basically different parts of the genome sort of switch in and switch out. And that can give the virus different characteristics. And so it could be that, you know, if there was a benign calisia virus present in rabbits, which we know rabbits, do have several benign rabbit calici viruses that just infect the gut, they don't cause that

systemic disease. And if that benign virus then acquired virulence, either through just standard viral evolution or probably more likely through a recombination event with something, then that could have led to the emergence of this highly virulent rabbit calisci virus. Similarly, with RHDV2, all known RHDV2s actually contain part of their genome from other rabbit colisea virus. calici viruses. And then it's the RHDV2 capsid that's the new part. And that gives it the broader host range and things like that. So the capsid is the shell of the virus. And so where those capsid genes came from, again, we don't know. Was it just through natural evolution or was it a recombination event with another calisivirus? So two main hypotheses, cross species jump or evolution

from a benign ancestor. So how did RHDV2 get to be globally distillery? because it was only found in 2010, but now it has this global distribution. So what do we know about how that happened? That's been the really incredible thing is seeing how RHDV2 has become globally distributed so rapidly. It's really been incredible observing this sort of in real time and a bit horrifying. So again, we know that it's an incredibly environmentally resistant. virus and so it can survive and remain infectious for months in the environment. And then I think the other thing that's contributed to that is that because there's not a lot

of cross-protection or immunological cross-protection between RHDB1 and RHDV2, RHDV2 very rapidly replaced RHDV1. So I guess the analogy here would be RHV2 is the Omicron of Ravit calisiviruses replacing Delta. And so, you know, there was this huge surge in cases because it swept through an effectively naive population. So you had huge case numbers. The virus grows to extremely high levels and infected rabbits. And so there was just this massive virus load being shed into the European environment after the emergence and local European spread. And so then with global travel and globalization, you know, if people walked across a park where a rabbit

had died, they pick it up on their shoes and then they travel and take it home, you know, and if it gets into a wild rabbit population anywhere, then it spreads that way. And I think we saw a similar thing with the emergence of canine parvo virus back in the mid-70s. Parvo viruses are also incredibly environmentally resistant and we saw that spread globally within about six months, actually. So we know that environmentally resistant viruses just through fomite transmission can, you know, on shoes and things like that. I think the other thing that I don't have a lot of data on, but I really didn't appreciate, I guess, so much before RHDB2,

how much trade of rabbits and rabbit equipment, particularly there are. So I think, you know, it could be that if somebody's pet rabbit dies, they then put the cage on eBay or something, and somebody else orders the cage, and then the cage is contaminated. And so, again, I certainly don't have direct evidence for that, but I think it's easy to sell stuff internationally these days and ship stuff. And so I suspect that there may be some of that as well. I want to talk about sort of the impact of RHDV2 in Australia in a minute,

but I want to first ask about some of these places where RHDV1 or RHDV2 has spread and where rabbits are not considered invasive, where they're just a part of the natural ecosystem. What have we seen in terms of the impact on the local rabbit populations there? And what kind of downstream effects have there been on the other members of that ecosystem? You know, the impacts of RHGV, first RHGB1 and now RHDV2 on rabbit populations and their native home ranges is really concerning. And it's actually caused them to be their threat category to be upgraded in terms of the IUC and Red List. So it really is a major concern for native rabbit populations. And so rabbits are native to the Iberian Peninsula, so Portugal and Spain.

And they've certainly observed 60 to 70 percent declines in rabbit populations. And then they've also observed similar reductions on their apex predators. So the Iberian links in the Spanish Imperial Eagle particularly because those animals don't have the food source. And that then affects fecundity of those populations. and so they're not breeding as effectively. And so rabbits really are keystone species in their native environment. Similarly, RHB2 arrived in the US in early 2020, and we've seen quite dramatic impacts on cotton towel

and jack rabbit populations in the US. And certainly there are several endangered species over there, and so there's quite grave concerns about the impacts of RHDB2 on those already threatened populations. Likely there will be similar lead-on effects on their, predators as well. I don't know that the reductions have actually been quantified at this point in the US. And I think the other thing, you know, I've had some conversations with colleagues in the US and they've sort of said, we haven't really seen the knockdowns that we, you know,

you've reported in Australia or that we're seen in Europe. And I think that's probably, at least partially due to the different ecology of the cotton tails and jack rabbits over there. So I believe that they don't form these massive Warren systems, the same way that rabbits do, the content Intact densities are probably lower and things like that. A lot of people who are concerned about this are not just concerned about the wild rabbits, but also sort of domestic pet owners. Is there anything good on the horizon or is there any good news on the horizon potentially for a vaccine or any sort of control, I guess either for both the wild rabbits or people

who have domestic pets? Certainly for domestic pets, good news with RHD or colise viruses is that really there's only those two types. So RHDV-1 and then RHDV-2. And the immunity induced, if you do if I have infection or after vaccination, is pretty much lifelong. Like, it's a really durable. It's a really strong induction of immunity. And so RHDV2 vaccines have been developed and are available in many parts of the world. And so for pet rabbits, if they're vaccinated, it's really not likely to be an issue. Unfortunately, in Australia, we don't currently have. to vaccine and that is a problem and something that is being worked on. In terms of wild rabbits,

I think that's a bit harder. You know, how do you vaccinate wild populations? I think is an ongoing concern from multiple disease perspectives. You know, certainly in the Iberian Peninsula, they're doing a lot of habitat management to try to help support rabbit populations. They're actually restocking wild populations. So moving animals from high density to impacted areas. And I think we now know, so in the last couple of years, it's clear that maternal antibodies, so if the mum has antibodies to RHDV2, then the kittens will be protected for, you know, sort of around an eight-week period. And if the kittens are infected during that time, then they don't die. They effectively get vaccinated. And so there was a really

interesting paper out recently. They actually spread RHDV2 baits in an enclosed population, in a control population, but they actually spread RHDV2 brates during breeding periods. And they actually showed that there was a reduction in young rabbit mortality by a third. And there were actually more immune juveniles recruited into the adult population. And so I think as RHDB2 becomes endemic and immunity levels increase, that maternal antibody protection will help buffer those impacts on rabbit populations moving forward, which is good for native populations. But again, in Australia, it's going to be an issue for biocontrol. In our mixomatosis episode, we talked a lot about the evolution of virulence, which is one of my

all-time, like, favorite things to think about, and how selection pressures are super dependent upon the virus itself and the way it's transmitted, the host behavior, the environment, among many other things. In the case of maximatosis, of course, there was this trend towards decreased virulence, and then more recently it seems like a few more virulence strains have been selected for. And then, of course, genetic resistance among the rabbits played a large role. And so I was wondering, you know, what have we seen in terms of any virulence changes of RHDV one or two since these viruses were first discovered?

And has there also been any genetic resistance among rabbits? it's such a beautiful example of, yeah, how each virus is perfectly adapted to maximize its transmission, right? And so, myxoma virus is spread by biting insects, and so therefore it requires a live animal to transmit. So it's, you know, in the virus's best interest to keep the host alive for as long as possible to maximize the number of biting insects that can feed on that infected animal. And so a prolonged disease duration is good. So hence the virus attenuates to become less virulent. In the case of RHDV, it's spread from that dead animal. Like I said, it's that carcass contaminating the environment and being exposed to blowflies

that facilitates transmission. And so as long as they die at the peak amount of infectious virus, that's going to optimize transmission. Hence, we really haven't seen attenuation of the virus with either RHDB1 or RHDV2 because, again, maximum transmission occurs by killing that rabbit at that 48-hour mark when the entire liver is just packed full of virus. And so I know there's been a lot of discussion about that virus has always evolved to be mild. And certainly I think this is a classic example of, you know, it really depends on the root of

transmission. And so in terms of genetic resistance, myxomavirus is a pox virus. So it's a very large DNA virus. And so it encodes a whole bunch of genes. And I guess that also provides a lot of targets for the host immune system. And so pox viruses have all of these. these really cool mechanisms of trying to counteract the host immune system and therefore the host evolves to then counteract the counteractions and et cetera, et cetera, and this really beautiful

virus host co-evolution. Because calisia viruses are so tiny, they just kind of, they get in, get it done and that's it. And so it's, yeah, a bit of a different story. There are some studies suggesting the development of genetic resistance in some localized populations to RHD 1, at least in Australia, but certainly it doesn't seem to be a major driving force the way that mizoma virus was. And again, I think that's because RHDV is just so lethal so quickly that there's not really the opportunity to survive. And I think what's really intriguing is the RHDV1, RHDV2 differences here, because RHDV1, while it was able to infect, it is able to infect young rabbits, younger than about eight weeks of age, it doesn't.

tend to cause disease in young rabbits. It only kills adult rabbits. And that's independent of maternal antibodies. So there's just, there's something about young rabbits that leads them to not develop disease after RHDB1 infection, whereas that's not true of RHDV2. RHDB2, Lathly kills both young and old rabbits. And so in the case of RHDV1, it was kind of a very stochastic or random event, like if you happen to be five weeks old when you got infected, you survived and if you happen to be nine weeks old, you know, you died. And so there's not really a strong selection pressure there. It was just a sort of a random event. Whereas with RHDV2, there's not that sort of age differential. And so previously just being young enough to randomly avoid

dying is not a thing anymore. And so the rabbits that survive RHDB2 infection, if there is a genetic component there, it's potentially likely that there will be a lot more, a stronger selection pressure for development of genetic resistance to RHDV2 than there was to development of RHB1. So it's certainly something that people are very keen and actively investigating to try to see how this plays out as RHDB2 becomes endemic. Here in North America and in many other places where rabbits are considered like a keystone native species, the arrival of RHDV2 has been met with these alarm bells, like, you know, concern for the rabbits.

This could be lead to a lot of ecosystem collapses. But in Australia, you know, where rabbits have been invasive for about 160 years or so, has RHDV2 been seen as a problem or more as a potential solution? And do you think that these differences in perspectives across different countries, do you think that that changes the way that research is done or focused on, the different types of research questions into this pathogen? Yeah, so RHDV2 was first detected in Australia and probably arrived in Australia in around 2014,

and first detected in 2015. And at that time, rabbit populations were certainly increasing, and we were actively investigating the release of a new biocontrol this K-5 variant that I mentioned briefly at the beginning. So, you know, rabbit populations were increasing. It was seen to be a problem, and population densities were very high. So when RHDV2 entered the Australian rabbit population,

as we've observed elsewhere, there was this massive epizuodic sweep through. And we saw population reductions based on, you know, serological data and spotlight counts and things like that is an estimated to 60% reduction in rabbit abundance nationally, like 60% population level reduction. So very considerable. From our perspective,

that dramatically interfered with all of the research that have been going on for the K-5 release, right? because we'd put all this modeling and effort into looking at how K5 would behave in the pre-RHDV2 rabbit population. And obviously, once RHDV2 swept through, population densities were much lower. They were probably a lot more fragmented. And so, you know, the effective reproductive number is totally different in different population conditions.

And so there was a very confusing aspect between, like, was this the new biocontrol that these scientists were talking about? And then we're trying to say, no, it was an indifferent strain that was just spontaneously came in and things like that. So overall perspective, it's dramatically reduced rabbit numbers, which has been very beneficial. However, it's certainly a problem for pet rabbit populations, because as I said, we don't have a vaccine here. We weren't expecting RHDV2. And so, like, again, for that K5 virus, we've done a lot of research into making sure that the vaccines were appropriate for that release. And then RHDV2 swept through and it's having really, really dramatic impact on

pet rabbits. And so an RHGB2 vaccine is certainly needed for Australian pet rabbits. In terms of the differences in research focuses between different countries, I think really it's all about understanding the pathogen, right? And then you can either use that to your advantage as a biocontrol or to your advantage to counteract its impacts. And so I think we're all actually doing quite similar research. It's just how those findings are applied. So the use of biocontrol is never without controversy. Can you talk about some of the reasons that people are opposed to the use of these rabbit viruses? And is there a possible downside to reducing rabbit populations in Australia? I mean, nobody likes killing animals, right? Like,

nobody wants to be killing animals if there was a better way, you know, 100%. So unfortunately, with the current technologies that we have, lethal control of invasive species really is the only way to manage that. And even, you know, you can't go around and surgically sterilise every rabbit in Australia and things like that. And even if you do, then they're still going to have those environmental impacts in the meantime. So, but of course, yeah, it certainly is controversial. There's a few different reasons why it's controversial. I mean, I guess obviously animal welfare, particularly. As we said, RHDV is very quick and there are minimal clinical signs, you know, although the pathophysiology sounds horrific, it's really your organs just pretty much

go into organ failure and you die very quickly. So the welfare is way better than something like Mixo. People have raised concerns about releasing viruses, viruses evolve, you know, will it spread to native species or other species or could it cross species? And certainly, I guess, with the many decades, at least with RHDB1, these viruses appear to be incredibly species-specific and we haven't seen any evidence of infection in non-legomorph species. Obviously, the impact on domestic rabbits is controversial and for that, as we said, we need a vaccine, but the vaccines are very effective when they're available. Possible downsides to reducing rabbit populations, I think one thing that's frequently raised is that if you reduce rabbit populations,

that would lead to predators turning to native species. And again, there's been quite a lot of research actually done investigating that. And there's been no direct evidence to actually support this prey switching by either feral or native predators in Australia. And so actually it was the opposite. Reduced rabbit abundance was showing to actually reduce feral cat and fox abundance and reduce the predation of native fauna because, you know, a large population of rabbits supports a large population of these predators. And so just by reducing the number of predators, by reducing the number of predators, by reduce. their food source was actually beneficial, but it is something that's quite frequently raised. And then just briefly, I think the other thing that perhaps is not so frequently raised by

opponents of biocontrol, but for users of the biocontrol, I guess the efficacy of the agent can be quite variable. So it depends on, you know, the virus dose that the animal receives, the level of pre-existing immunity, the maternal antibody status. And it really needs to be used at the right times. And so the, a little bit more finesse than something like putting out a poison. So one last question about RHDV2 biology and so on before I get to ask a bunch of questions about you. And that is the impact of climate change. So what do we know or what is thought to be the potential impact of climate change on rabbit populations

or on the distribution of these rabbit viruses in Australia? You know, rabbits are known to be really adaptable. their native range of that Mediterranean ecosystem, but they've really managed to adapt to a lot of Europe. There's feral rabbit populations in British Columbia and Canada. You know, they colonized Australia within a 70-year period. So they are really adaptable. And so if the rabbit populations thrive

and particularly in adverse environmental conditions, then this is going to really have more impacts on our native plant and animal species. And so for the viruses themselves, as we said, they're pretty environmentally resistant. But again, if we start to see these really prolonged periods of drought, then that's going to probably reduce the environmental burden of these viruses. And I think we're probably already seeing some of these impacts in terms of the variability that we've seen over the last few years.

So over the last couple of years, we've had a Lanina event in Australia. so a lot of warm, wet weather. And certainly the last two years, we've seen really massive outbreaks of calisia virus in spring when those fly vectors start to increase, but I would assume that drought may then reduce environmental survival. So there's probably arguments both ways on how that would affect the actual virus,

but certainly I think rabbits will survive or adapt to climate change a lot more readily than our native species, which is a concern. So we're going to take a quick break here, and then when we get back, I want to ask you what it's like to work in the rabbit biocontrol program and what a veterinary virologist does. I'm so excited. Thanks. 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. 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.

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No, sorry, I do basements. Connecting homeowners with skilled pros for over 30 years, Angie, the one you trust to find them when you trust. Find pros for all your home projects at Angie.com. Welcome back, everyone. Okay, so I want to know, as the team leader on the Rabbit Biocontrol program, what do you end up doing on a day-to-day basis? Or maybe it's more accurate to ask you how much does what you do change from day to day? Yeah, so I think, you know, what's really exciting about our team or the research that we do is it spreads quite a few broad areas. So, you know, we do animal experimental work, so infection trials, and then we do a lot of in vitro work.

Polisi viruses notoriously don't grow in cell culture. And so we're trying to establish an organoid system for these viruses. So there's some, you know, molecular biology, there's cell culture, there's animal experiments. And then there's field work as well. So we get to go out and sample rabbits in the field, which is lovely. And then there's a lot of molecular surveillance and diagnostic testing as well. we really have broad techniques and are able to do a lot of variable things that that keeps life interesting. For me, as team leader, I'm not really in the lab so much these days, which is

quite sad. But, you know, like many sort of PIs, I guess, I'm working across several projects, you know, working on the next grant, working on the next publication. I'm also a facility veterinarian here. So I respond to animal emergencies. And yeah, you know, know, life's never dull in science, I think. Yeah, that's right. You practiced as a veterinarian for a bit, and you are still practicing as a veterinarian, which is amazing. So can you take me through how you got from veterinarian to veterinarian and veterinary

virologist? Lots of V's in that sentence. Lots of V's, yeah. Made it through. Yeah, so, you know, I was one of those kids who was always curious, you know, I was, why, but why? but why, but why? And, you know, I loved nature. I loved animals. And so I, from a very young age, I said, I'm going to be a vet. And so that's what I did. And I actually thought I was going to be in small animal practice for the rest of my life. And I got into small animal practice. And, you know,

I think I found that I wasn't really asking why so much on a day-to-day basis. There was a lot of routine and, you know, there's a lot of other considerations. And so that sort of, that curiosity wasn't satisfied the way I had expected it to be, I guess. And so to me, that lent itself to going back to do a PhD. And when I was applying for PhD programs, you know, looking back, everything I applied for was an infectious disease of some sort. And so I'm guessing that infectious diseases piqued my interest somewhere along the line. And, yeah, ended up doing a virology project working on recombinant vaccines for the poultry industry. And yet, from there, I just fell in love with viruses. Like, they're just, they're so cool and they're so diverse. And heaps of different

opportunities have stemmed from that. So after my PhD, I worked for a period of time as a diagnostic virologist in one of the state labs and then went back to do a postdoc in Rabat-Khalisi viruses and, you know, like we've just talked about, they're so cool. How, you know, is there so much to do? So I've stayed, stayed since. Do you have a favorite virus or bacterium? I'll allow that too, or parasite. Well, I mean, I probably have to say RHDV, don't I? You don't have to, but I would think that that's a very strong contender. Yeah. Yes. I just, you know, I think, yeah, viruses are also perfectly adapted to their niche, right? And so every single one of them has such a cool story to tell. So, I mean, I think perhaps one of the coolest ones is, you know, Sinsittin.

So Sinsittin gene, which is the gene that allows the development of placenta, right? It allows the cells to fuse, which is the basis for the, you know, for placental development. Sinsittin is a captured retroviral gene from a human retrovirus, right? And that that allowed the evolution of all placental mammals. So I guess I kind of have to say Sinsittin, otherwise I wouldn't be here, you know, or whatever virus gave rise to Sinsitton. And also, you know, I would hate to live in a world without my dog. And so, you know.

But yeah, you know, viruses have just shaped evolution so strongly. And so every single one of them is just amazing. And, you know, there's those polydnaviruses in parasitoid wasps that they inject the virus along with their eggs that suppresses the caterpillar immune response so that the caterpillar immune system doesn't kill the egg and things like that. And then there's a microvirus that infects a fungus that infects rape seed, which turns the fungus from virulent to actually beneficial for the plant and things like that. And so they're just, I mean, I can't pick one. There are just, there's so many cool examples. You just gave some of the most fascinating examples that

I don't think I've heard of any of those. And so that is like I am about to go after this is over, I'm going to go like on a Wikipedia rabbit hole about every single one of those. And I'm very excited. Worth it. Totally worth it. So you work at CSIRO, which is a government institution. And what do you think are some of the pros and cons of working at a place like CSIRO versus like a

university for instance? Yeah. So I think, you know, one of the things about working for Sari that I've, I've, really enjoy and that really vibes with my values, I guess, is the really applied focus. You're doing research because someone or an industry body has said, this is important to us, can you look into this? And so they're really applied outcomes that end users really care about. It's really output driven. And you really do get to work closely with stakeholders. So, you know, setting the next research agenda, it's like, okay, well, how do you feel about what we've done so far? What, like, where

we go from here. And so it's, it's a real, really collaborative approach with the end users, which is great. You know, the flip side of that is that there are really strict milestones and deadlines. And there's not so much of the opportunity to sort of just follow the science for the sciences sake that perhaps you may get in an academic institution. Similarly, it's a lot harder to, I guess, pivot. So for example, with the whole coronavirus situation, I know so many virology labs, you know, just completely pivoted to SARS-CoV-2. And obviously, like, that was never going to be an option because, you know, the agriculture industry isn't going to, they have a rabbit problem.

They still have a rabbit problem. So, yeah, pros and cons, you know, they're both the same side of the coin. It's really achievement-focused, but then it's a little less curiosity-driven, I suppose. On the podcast, we're always talking about One Health and how much we love it and how important it is for different fields to work together to consider the whole picture. And so do you feel as though your experience as a veterinarian has given you more of an insight into the One Health approach? Yeah, I really do. I think, you know, at vet school and in practice, you have to have your head both around the individual level, treating the individual animal, but also how that impacts the

herd and the population and interspecies level as well. And so I think it's just drilled into us and we've never considered otherwise that, you know, how does what I do here? How is that going to impact the rest of the ecosystem? And, you know, and again, from the veterinary perspective, it incorporates nutrition. And in terms of large animals, that incorporates pasture. And so that involves drought because then different weeds will pop up with different climactic conditions and things like that. So I think training as a veterinarian really gives you that broader.

perspective of the animal but also the environmental and then the human and zoonotic disease picture as well. So can you tell me about a cool project that you're currently working on? So perhaps I may have given away a bit earlier, but the whole recombination story has just, over the last couple of years, has really piqued my interest. So as I mentioned, RHDB2 first arrived in Australia, probably in 2014. And we've been tracking the genomic epidemiome of these viruses since it arrived. And what we've seen through that genomic surveillance is at least six independent recombination events since the arrival of RHDB2 in Australia. And that's just the recombination events that have generated epidemiologically fit viruses,

right? Not all the viruses that died out. So that's unprecedented, or at least I didn't appreciate it prior to that, how important recombination was. And then seeing these successive waves of epidemiological replacement by these variants. And sadly, I think it's been superseded now by the coronavirus variants and everybody's like, well, yeah, what did you expect? But for me, it was really striking when I saw this with caliciruses. And I think what's been really intriguing, so among those six recombinant variants that have arisen, they all contain almost identical capsid proteins or, you know, effectively the spike protein to each other. So it's not immune escape that's driving this epidemiological replacement of these viruses. And so if it's not

immune escape, like what is it? Because again, there's all this focus on immune escape. And so we recently had a got funding support for a postdoctoral position to start to try to look into what is driving the epidemiological fitness of these recombinant variants. So which of these non-structural proteins and why? If it's not immune escape, what is going on? And so I think that's really got my interest at the moment. All right. So I've got one last question for you. And that is an advice seeking question. What advice would you give to someone who is interested in pursuing this type of career? Or maybe, you know, what type of advice do you wish you had received when you were just starting out? You know, in hindsight, looking back, you know, I think there's a lot of talk now

about this fixed mindset versus growth mindset type thing. And I think, as I said, I decided from a really early age that I was going to be a vet. And so I guess my whole identity as, you know, through my school years and then going through vet school and everything was like, I'm going to be a vet, I'm going to be a vet. And that really fixed mindset. I mean, it was good, obviously, like you need to have the drive. But it also, you know, it probably made me pass up or bypass other opportunities that may have popped up in the way, along the way. So I think in hindsight, you know, if I I could have adopted more of a growth mindset instead of this focus on being a small animal practicing veterinarian.

It could have looked really different. So I would just say my advice based on that would be be open to opportunities like, you know, have a plan but be prepared to adapt it. Be curious. And I think for me it was really important finding out what my values were. And, you know, as I sort of briefly mentioned, reconciling that practice wasn't satisfying that core curiosity value that is so strong for me and knowing that there's other things out there where you will be a good fit sort of thing. And so, yeah, be open to different directions

and yeah, just be curious. That was so fascinating. Oh my goodness. Thank you so, so much, Dr. Hall for chatting about rabbits and viruses and evolution. I had such a great time. If you want to learn more about the work that Dr. Hall is doing, I'll link to the project's website as well as a bunch of cool articles related to Dr. Hall's work on the post for this episode on our website, this podcast will kill you.com. Speaking of which, you can find all sorts of things on that website, including, but not limited, to the sources for all of our episodes, transcripts, our bookshop.org affiliate account, our Goodreads list, music by Bloodmobile, links to merch and Patreon,

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And a special thank you also to our wonderful, generous patrons. We love you. We've got another regular season episode coming out next week. covering a whole new topic. So until then, keep washing those hands. Why have I asked my age-fat guy I found on Angie.com to change my grandpa's tracheot tube? Because I was so amazed by how quickly he replaced our aerodox.

I knew I could trust him to change Pop-Pub's tube while I was on vacation. Make a quick, young man. Aw, see, Pop-P trusts you. I think we should call it doctor. Connecting homeowners with skilled pros for over 30 years, Angie, the one you trust to find the ones you trust. Find pros for all your home projects at Angie.com. Success starts with your drive,

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