Baa's and Bleat's - The AASRP Podcast
Baa's and Bleat's - The AASRP Podcast
Catching up on CWD with Dr. Catheryn Haigh
Join us for a discussion about the latest research in Chronic Wasting Disease in cervids.
In this episode we talk with Dr. Catheryn Haigh with the from the Chief Prion Cell Biology Unit at the Rocky Mountain Laboratories, National Institutes of Health. We do a little looking at CWD's history, the current research and where it is going.
Questions can be sent to Dr. Haigh at cathryn.haigh@nih.gov
I said I would put a note about testing on deer farms. From what I can find as the only certified test is done during a necropsy any animal that has shown symptoms of CWD should be tested and the entire herd may be depopulated. But actual requirements vary by state.
If your company or organization would like to sponsor an episode or if you have questions about today's show, email Office@AASRP.org
Welcome, welcome to our next episode of Bosen Bleats, the American Association of Small Ruminant Practitioners podcast. Today we are talking with Dr. Catherine Haig of the Chief Prion Cell Biology Unit at the National Institute of Allergies and Infectious Diseases at the Rocky Mountain Laboratories. Thank you so much for joining us, Dr. Haig. Thank you very much. It's a pleasure to be here. So let's start with a little history. I always love to hear where people are from, where you got went to school. You are my first non-veterinarian guest. You are a doctor, but not a veterinarian, a PhD. So give us a little bit about your background.
Catheryn:So I'm originally from England. My secondary education was in really a small town. And while I was still in school, a disease emerged in cattle called bovine spongiform and cephalopathy or BSC. The media dubbed it mad cow disease. And it eventually transmitted to humans, which as a child was incredibly scary. When I went to university, I decided to study biomedicine. I went to the University of Cardiff and I did a training year in the National Health Service in diagnostic laboratory science. And during that time, we had a patient that had this disease, which was Kreutzwelt-Jacob disease, that was thought to have come from VSE. And this patient, everyone was so scared. So by this point, I am absolutely caught in the fascination of these diseases. And I opted to do a PhD at the University of Bath studying them. And by the end of my PhD, I didn't want to give up the research area. And it just so happened there was a job at the University of Melbourne in Australia. And I went out to that job. I had a one-month contract and I stayed for 11 years. And then again, just by luck, the job at the Rocky Mountain Laboratories here came up, and this is where I've been ever since.
Sarah:Wow, that's interesting. So you've been obsessed with prion diseases from for for many years now. Okay, so I am going to briefly dive into a little bit of explanation about what we're going to talk today about, which is chronic wasting disease, or we'll call it CWD from here on out. So you we're not going to talk about a specific paper like we have in the past. We're just going to kind of talk about this topic more generalized, and Dr. Haig is going to kind of talk to us about the latest research and different things that are coming out about it. So let me just give you just a slight background. Most of our vets are going to know most of this, but some of our producers, maybe you don't. Okay, so chronic wasting disease, it's a disease in cervids, which we usually think of, especially with CWD, being deer, moose, and elk, and different, different deer and different, different species breeds of deer and elk, and the moose get it depending on where they live. And Dr. Haig is going to correct me if I misspeak, so hopefully I won't. So CWD was first identified in the late 60s. It's currently thought to be in about 30 states, parts of Canada, and a few other countries. And most of those countries have got it from importing deer from North America. It's what we like to what we call a transmissible spongiform encephalopathy, and it's a cousin to scrapie in sheep and BSE, or as Dr. Hayes said, mad cow disease in cattle. The path of transmission or spread between the different cervid populations, it's still a little unclear. A lot of the research is being done on that. But from what we know so far, it can be transmitted through both body fluids and body parts. It can be transmitted directly by both horizontal, so from dam to offspring, or no, that's vertical, dam to offspring, and horizontally between herdmates. It can be spread indirectly, such as from an infected substance that's in a field and then grazed by other deer. So if say a hunter opened up the deer, took out the insides to make it lighter to move back to his vehicle and left, you know, the innards of the deer, and then that rotted, and another deer came along later and grazed that area, that could be a site of infection. The most clinical signs, obviously wasting, like in the in the name, but chronic weight loss, and there also can be neurologic signs in the animals. And then obviously on necropsy, many lesions in the brain. The prion diseases are always fatal and there's no treatment as of now. So these are just some of the basic facts. And as we go, we'll jump in a little deeper and talk about what's changing in research.
Catheryn:We see more cases in bucks, probably due to the tendency to fight. Okay.
Sarah:Interesting, interesting. Let's just jump in. And if you just want to talk to us about the latest research, where research is going, what you guys are finding, new testing. Yeah, just kind of let's let's hear what's going on with CWD work.
Catheryn:So a lot of my research really focused on the human diseases. My interest in the human disease that was transmitted from cattle was really what pulled me into being interested in CWD. All of these diseases are caused by a unique infectious agent. It is entirely different to a virus or a bacteria. It is not seeking to replicate itself. It doesn't have a genome. It is actually simply a protein. And it's a protein that has become this folded and changed shape from what it should be. So all of us have this normal protein. We don't know what it does, but it's within everyone. During disease, when that shape change starts, the new shape is then able to bind to more of the normal proteins and cause an ongoing cascade of those shape changes. This is how it transmits through the brain and from animal to animal. So the concern of our research, of course, is how does that transmission occur? Could CWD jump from animals to human? And in the context of humans, what actually goes wrong in disease and how does the brain die? We see the accumulation of these misfolded proteins, but we really don't understand why that accumulating protein causes the brain to die. We don't understand that in CWD or in human disease. So when my group first started working on this, our particular objective was to create a human model of disease. There hadn't ever been a human model. Human cells are very hard to infect. And what we did was we took human cerebral organoids, which are spheres of human-like brain tissue that we grow in a dish. It's an extremely ethically appropriate technique because we actually grow them from induced chloropotent stem cells. And those are cells that we have made from skin cells. We actually take SNPs and we re-engineer them to be these chloropotent stem cells, which we then turn into brain cells. And doing that, we've been able to create this completely human model that we can infect with human prions and we can actually monitor the disease progression, how it damages those organoids. That specifically was what led us to CWD, because we have never had a model where we could look to see if CWD could infect human brain tissue. The nearest models that we have to humans are actually Mogus macaques, or at least the nearest model that I believe has been tested for CWD. Fortunately, the macaques did not take up infection. So that was a very good sign that we have a very strong species barrier to this disease being able to jump to humans, unlike BSE, which very clearly did go into macaques. In our brain organoid model, we tried similar experiments and we put the organoids into a media environment full of CWD prions to see if they would infect the human brain tissues. And very fortunately, we did not see any evidence of infection in that model.
Sarah:We were, you and I were talking before we started that scrapie, which is another prion disease, has not jumped to humans and it's been around for a very long time. So it's another good good kind of example that we can take away that not all prion diseases jump, can jump into humans. What has Scrapie I what species has can Scrapie go to? Do you know? Scrapie is sheep and goats. And that's it.
Catheryn:I believe that experimental trans transmissions to cattle have also occurred, but I'm not entirely familiar with that data. Okay.
Sarah:Sorry, that that was kind of a curveball question, but so yes, so macaques have been the closest model, and yay, it doesn't go to them. So one positive way.
Catheryn:Yes, uh Scrapie has been known of since the 1700s, and we do not know of any case of it transmitting to humans, which is a very good sign that certainly not every Prion disease would.
Sarah:Okay, so your research focuses on the movement to people. Can you talk a little bit about, just because we're veterinarians, that's the audience, what we can do for the deer? So what what kind of actions are out there? How are they trying to slow the spread? Is there, you know, in the states that it's very prevalent? What do you know kind of what that action plan is? If there's what are people talking about as a hope for slowing this down?
Catheryn:By my understanding, some states have more developed action plans than others. I think the best thing that anyone can be doing, the hunters, really at this point is testing. The testing the carcasses to understand how far this has actually gone, how badly infected herds are. Because we really we don't have any intervention measures. There have been various culs trying to wipe out herds where CWD is. But the problem is because it is so infectious in the environment, it can transmit potentially years after an animal has died and rotted in the ground. There really isn't a way to clean an area so that it won't transmit again. So understanding how far it's spread is probably the first step. There are a number of groups that are looking at vaccines. I believe there's some promising results, but I don't know how far they've come along yet. That would be really quite wonderful if we could do that, because if we could vaccinate the deer and they could no longer get the disease, it would gradually disappear. So that would be really our best case scenario.
Sarah:And correct me, I think what we were talking about before, there is a way to test living animals, correct? Yes, it doesn't just have to be brain tissue. No, um, if you were had a farm herd that you were farming, you could test your herd. Yes.
Catheryn:And I believe people do. The tests for this have come on in the last 10 years amazingly. Whereas it used to be pretty much a post-mortem diagnosis from brain. Now we're sort of looking at clippings from ear tissue. And the tests are much faster. So there really there is no good reason not to get the animal tested if you're worried about it. And certainly, I would hope that we might move captive herds to routine screening at very low cost. I don't know that if that's in the works yet, but certainly these tests are really, really good. They're very sensitive, they're very specific. So we we have moved into a new era of good testing for these diseases.
Sarah:Well, that alone, I would think, would stop it from going to these other countries, right? And I mean, from what I was reading, and you know more than me, but it's a couple Northern European countries have found it, and like South Korea or something super random like that. So if the testing is easy, you can do it on living animals. Hopefully that won't happen again, right? Like that should be a requirement.
Catheryn:We would hope that. Part of the caveat to this is that I think we don't know how early an infection that we would be able to pick up. That is work that is certainly being done right now. So you you would need to know how early you could detect infection in those animals and maybe test them over a period of time to make sure they didn't go from negative to positive. But certainly there is work being done trying to figure that out in the animal models now.
Sarah:Right. They could be like silent carriers. So yeah. And I'm sure we're working to the, like with so many other animal diseases, the clean herd, where you know, you've tested over the years, you've had a closed herd, nobody has come and gone, you know, you're not borrowing someone else's buck for breeding. There's no way wild animals are getting in with your farmed animals. So hopefully, yeah, the clean herd scenario, I would hope, is maybe the way we're going.
Catheryn:Yeah, certainly in a captive herd where they're in such close proximity, it's gonna spread fairly quickly. So screening prior to moving the herd would be very valuable.
Sarah:Yeah, yeah. All right, so we're working on and have achieved better testing. Uh identification has been a huge part of the scrapie solution. I spend a lot of timing about scrapie tags and all of that in my in my field of this world. Do you know anything about that aspect?
Catheryn:In terms of the scrapie field, there was an awful lot of breeding to try and breed flocks that were resistant to disease. I believe there was some element to success, but even the most resistant genotypes were still found to take you know that some sheep would get disease. So that a similar approach was considered for CWD, but I don't think I've seen anything to suggest that it's been successful. I think a lot of the research has really focused on the transmissibility. There has been some very interesting research on decontamination because it contaminates the soil. So an interesting one that I read was that mountain lions, when they eat a deer, they actually digest away a lot of the infectious protein. So by eating that deer, they're kind of purifying the landscape a bit. And there are even some worm models that look at how worms can decontaminate. So there's been a number of angles like that and a number of angles just looking at decontamination agents for if you've prepared a deer and then you find out that it was infected. There are a few new papers on that which have found various substances, even household substances, can be effective. I think at the moment we tend to use quite concentrated bleach, but that should be pretty efficient on most equipment. So yeah, those those studies are definitely ongoing. How to decontamine how the environment might decontaminate these, as well as how we can decontaminate an area that might have had a infected deer in the world.
Sarah:I think what does where does composting fall in that?
Catheryn:I don't know. I would think if worms are able to reduce it, it might be it might be a good thing that if that's being tilled and turned over, that it would reduce the infectivity. So, but yes, I I don't know the answer to that one.
Sarah:Well, the I need to look up that study. I'm sure somebody has looked at that because so many people in my area out here, a lot of people are farmers, and so they just compost, you know, the remains of whatever deer they've hunted that year. You know, the skin and all the stuff they're not freezing. I don't I guess I don't know what, you know, if you take it to a processor, how they're disposing of the remnants. Probably burning it, maybe. That's probably pretty good.
Catheryn:Incineration does kill prions. So that's what we use for a lot of high-end infectious material. So I I would think burning biases has been generally a way to go if they're known to be infectious anyway.
Sarah:And and that's how they cleared out BSC positive farms in England, right? Yeah. Okay, so transmission, decontamination, testing. What are we missing?
Catheryn:Well, there will be a lot of research going on on how the disease spreads through the animal and kills them. Again, that that comes down to the question of can we stop it realistically, if vaccination worked or if we could stop these diseases, then the issue goes away on every level. There's no issue of transmission across species barriers. Once you've treated enough animals, the transmission rates would stop. So uh I know of some groups doing some really very cool research looking at models of deer brain, trying to understand how the prions are causing the brain to dysfunction. And this is very similar to what we do with the human tissues. Because there may be a way to stop this that doesn't need to be a vaccination. There may be a way to treat the disease and stop it. Of course, that may be more challenging in deer because you know, in humans, you're kind of looking for an injection or a tablet form in deer that might not be that simple, but certainly there's gonna be a lot of work looking at how we can stop this.
Sarah:And you look back, and we've been successful with so many diseases, so we just gotta get these brainy people like yourself plenty of money so they can figure it out. This is gonna be another like side question that you may not have an answer to. Does it seem odd that the prions are primarily in ruminants?
Catheryn:I don't know. Human diseases are natural too. I'm not I'm not sure that that really is the case. I think we've just observed the spread more in ruminants. In human diseases, that these agents are not like transmissible through saliva or bodily fluids, so we we don't have those same. Issues of transmission that we do in the cervids and in the sheep. A mad cow disease even was less transmissible. The reason that that spread so widely was because cattle were being fed back to cattle in their meat and bone meal feed. Otherwise, that that disease may never have emerged as it did. Cattle do have a couple of natural diseases as well. They usually onset much older. So yeah, I mean human diseases have been shown to be transmissible between people when ritualistic cannibalism was involved. And that was the Fori tribe of Papua New Guinea. They discovered a disease called Kuru. And it transpired that their funeral rites involved consuming the disease to purify them on their way to heaven. Otherwise, our diseases really are not that transmissible.
Sarah:It just is it's weird to me that it's like humans, sheep, deer, cows. You know, it's like, and maybe it's because we farm them and there's so many.
Catheryn:So it went into cats. I believe dogs and rabbits are the ones that seem particularly resistant, but we don't have any idea why.
Sarah:But obviously, like our goal with all of these prion diseases is not to scare the public away from eating meat, you know, hunting, consuming dairy products. You know, we're still here trying to keep them safe. And obviously, this is the focus of your research. I definitely didn't want to completely shy away from the zoonotic potential of this disease, but it's really, really a gray area. I mean, that's what you've been talking about and most of your research is about. But if you could kind of sum up that grayness and why it's not black and white for us, maybe that would be a little helpful.
Catheryn:Yeah, so BSC was very clearly not a gray area. It transmitted to people. It was clear that it transmitted in all of our animal models. We have mouse models of the disease, we have Cinemogus mechanic models. BSC very clearly went across. For CWD, it's been much less clear. There have been a couple of mouse studies where it has looked like there was some potential for it to jump. And the difficulty with mouse studies is that if you force a system very hard, you can definitely make it do what you want. That doesn't necessarily mean that it's representative of the real world. More promising results were the Cinnamonus mechanics, because they are a closer relative to us, evolutionary speaking, and they did not take up the infection. They were over many years not seen to get sick from CWD. And so then our data coming in at the end with the human model supports that we theoretically are far enough away from deer and servids' relatives that it shouldn't jump into us. But we can never say that it absolutely won't. There are a few things that we can't account for, and one of them is the emergence of new strains. So we can test the strains we currently have, but we obviously don't know what might emerge. And if something emerged that had more of a capacity to jump the species barrier, that would be something unfortunately we wouldn't know until the strain was already out there. If we do see any new strains emerge, that is something we intend to be looking at fairly quickly.
Sarah:And part of the thing that muddies the water is that there are news agencies, other people reporting that there are people that have, and I'm gonna mess up the disease, the prion disease in people. You say it very nicely, I'll let you keep saying it. And they they are attributing it from hunters and stuff, getting it from eating deer, but the science isn't backing that. And so that's really what muddies the waters for us, right?
Catheryn:You are completely right, it does. Because there has been so much fear over this, where someone who has a history of hunting does die of these diseases, there's been a tendency to overhype where it may have come from. The reality is these diseases do kill humans. We they're quite rare. I think it's usually one to three cases per million, but that's still cases that occur, and that hunter statistically has the same chance of getting the disease as the person who doesn't hunt. So these cases do occur. I think in the last media report that I saw that was um talking about this, it as far as we could tell, and I think the CDC put out a statement on this, it looked like the person died of a normal Kreutzvelt-Yakov disease, which what's the most common form of these diseases in humans? There was no evidence that they'd actually definitely eaten infected meat or when that would have been. So when mad cow disease crossed the species variant, the disease that it produced in humans was a variant of Kreutzvelt-Yakov disease. And that variant was different. So unlike the disease that we usually see, it affected people much, much younger. And the biochemistry of the disease, that was completely different to what uh the disease that occurs sporadically is. So we were able to see I think after four or five cases, it was clear that this was a new disease that had emerged. And what we might expect is that if CWD did grow across the species barrier, that we wouldn't see just the same disease as would occur in sporadic, yeah, in the sporadic cases of this disease. We would probably expect that we might see something much more like that variant disease that would look different and would affect people differently. So yeah, conflating the normal disease, which we do have people do unfortunately get it with a disease from infection. So far, when we've seen it, it's been a very different disease. And that was just BSC.
Sarah:I think that's a great piece of information to take when people are hearing stuff in the media and the news. And I mean, that's kind of our point, right? As the doctors, as scientists, to be like, yeah, we see what you're seeing, but like, let us shine some light on that. You know, let us give you some more information to make correct assumptions about these diseases and what's going on with them. And not, and one thing I always like to point out is, yeah, we may change our mind tomorrow because we have new data, but it doesn't make us wrong today. We're still, you know, saying what we know best. We're not hiding, we're not trying to be deceptive to anybody as a scientific community. We're just giving you what we know today. And I think that's really important for people to hear again and again and again.
Catheryn:Absolutely. If we find any evidence that will be put out as rapidly as possible with advice for how people should proceed. Um, there are whole working groups monitoring this all the time at the moment.
Sarah:All right. I feel like we've done a great job kind of updating everybody on what's going on. I've learned a ton. Is there anything else that you think we've missed?
Catheryn:No, I don't think so. I would simply reiterate to everyone test, test, test. The more knowledge we have, the better, really.
Sarah:So, do you have any specific advice? Because many of our AASRP members who this is primarily created for have deer herds. Is there any very specific things you would say to them? Like, and maybe you don't know this, because I know this isn't your specialty of CWD, but like how often they should test? Is it 100% of the herd? Is it, you know, a lot of times we test a percent of a herd to get a feel for it. When you say test, test, test, can you give our dear veterinarians any specifics on that?
Catheryn:I have not read the latest guidelines on what would be expected. I mean, any animal that's not looking particularly healthy, I'm sure would be a candidate to be tested. I would very much think in a captive herd that if one animal was found to be sick, then you would probably want to test the rest of the herd and find out how far it had gone. But I do not know the specific guidelines as they stand at the moment.
Sarah:So look them up and put them in the um podcast notes. Um I always ask our final question, and this can what do you see as the next problem that researchers need to think about and address in cervid medicine? So what where does where does our CWD research money need to be directed? You what do you what do you think's like I think even though the risk to humans for transmission across the species barrier is low, this disease being in cervids is just not good for the animals, it's not good for the environment.
Catheryn:I think we really need to try and find a way to stop it. And my personal excitement is certainly the vaccine research. That I've seen some very promising vaccine research, and I would love to see that pushed forward to something that really might make a difference to the spread of these diseases.
Sarah:Yeah, that would be absolutely huge. Great. Yeah, I agree. Well, thank you, Dr. Haiggs, so much for joining us. I know this was kind of out of your comfort level talking to a bunch of veterinarians, but I really appreciate you taking the time. And thanks so much for coming. Well, thank you very much for having me on.
