University Place

Discovering New Pathogens in Wildlife

– Welcome everyone to Wednesday Nite @ the Lab. I’m Tom Zinnen. I work here at the UW-Madison Biotechnology Center. I also work for the Division of Extension and Wisconsin 4-H. And on behalf of those folks and our other co-organizers, PBS Wisconsin, the Wisconsin Alumni Association, and the UW-Madison Science Alliance, thanks again for coming to Wednesday Nite @ the Lab. We do this every Wednesday night, 50 times a year. Tonight, it’s my pleasure to introduce to you Tony Goldberg of the School of Veterinary Medicine. He was born in New York City in Manhattan. He went to high school at the Westhill High School in Stamford, Connecticut and then he studied biology and English at Amherst College in Massachusetts. He got his PhD at Harvard in physical anthropology.

And then went to the University of Illinois in Champaign-Urbana to get his DV, Doctorate of Veterinary Medicine and his master’s degree in epidemiology. Tonight, he’s here to talk with us about something quite germane, given the coronavirus outbreak. The title of his talk is “Discovering New Pathogens in Wildlife “from Wisconsin and Beyond. ” Please join me in welcoming Tony Goldberg to Wednesday Nite @ the Lab. [audience applauding]

– Well, thanks very much Tom for the invitation and to everyone for coming tonight. Back when many of us were younger, our relationship with nature was quite different from it is today. It was an enchanted kingdom of sorts, but clearly that’s changed. [audience laughing] We live in a different world, a world in which our relationship to nature is more microbial than magical. This New York Times Magazine illustration shows us connected to the natural world through a highway of deadly pathogens. So it is indeed timely that I’m giving this talk today because we are in the middle of yet another pandemic.

This one caused by a novel coronavirus from Wuhan, China. This phenomenon really is new to science in a way. When I was doing my graduate studies, this idea of emerging infectious disease really was not on the scene. This is a graph of the frequency of that phrase in the medical literature by year since 1980, and you could see it didn’t really even figure in to science before the early 1990s. And then it sort of has taken off in this upward trend. I was doing my graduate work then, and I am pretty sure this can be attributed to the remarkable story of the origins of AIDS. That in the early 1990s, we discovered that AIDS was a virus that originated from chimpanzees in Central Africa, and really that decade between the early ’90s and the early 2000s filled in the elements of that story so that to me, the HIV pandemic is the mother of all pandemics, and the mother of all diseases of zoonotic origin. So chimps, very important. And that’s why even though this is a talk about Wisconsin, I’d like to start in Africa where I’ve done work for many years, including during my PhD years in a national park in Uganda called Kibale, which is famous for its primates. And most notably its chimpanzees, as shown by these lovely photographs by my colleague Ronan Donovan.

The chimps of Kibale are famous and have been studied almost as long as the chimpanzees at Jane Goodall site at Gombe. And they’re wonderful creatures, but they suffer problems. We recently did an analysis of causes of death over the decades of this chimpanzee population and found that respiratory disease, which was a little surprising to us, accounted for over half of the documented deaths during the time that we’ve been able to follow these chimps daily. And this came home to me in 2013 when I was there during a remarkable epidemic of deadly respiratory disease, where we lost 5 of the 50 chimps in the community shown here. And I’d known many of these chimps my whole career, like Stout, for example, charged me when I was a graduate student, and I’ll never forgive him for that, but I still miss him. The course of the epidemic was this. There were three waves beginning in about February of 2013 and ending in about September. And being there, it was very scary because when chimpanzees are coughing and sneezing and dying, you’re not sure what’s killing them. So in situations like that, you have to be very careful about wearing personal protective gear, sort of the moon suits. This is, again, me looking like a superhero thanks to Ronan’s fabulous photography, but you have to be very careful.

So we’re investigating this outbreak, collecting biological samples for analysis back in the lab. So what do you do if you don’t know what’s killing wildlife? It turns out that many years ago, there wasn’t much you could do. There were traditional diagnostics. You could say well, maybe it’s this bacteria, and maybe it’s this virus, and you’d send the sample off to a lab, and you’d get a yes or no answer back. These days, things have really changed, and that’s gonna be a theme that goes throughout this talk. Namely, we can rely on techniques now that are broadly known as metagenomic techniques as shown in that figure. Basically, we can take our chicken or rat or human or swabs from a sick chimpanzee and randomly sequence millions upon millions of molecules of DNA or RNA in those samples, and then feed all those sequences into a computer that will tell us what’s there. Most of it will be your salamander or your person or your chimp, but hiding in there, kind of the proverbial needle in a haystack, will be the thing you’re looking for, and you don’t have to have any prior knowledge of what it is. So these techniques are sometimes called agnostic or unbiased, and they’re very powerful. They’re the future of infectious disease diagnostics.

So we did this. This is something that at the time, I had just begun to do in my lab. Now we do it routinely. And out popped a remarkable answer. It turns out that these chimpanzees had been dying of a human pediatric virus called rhinovirus C. Rhinovirus C is the most common cause of the common cold in people worldwide. And this is a great story about UW-Madison because as soon as I realized what the culprit was, I only had to glance out my window down the street to realize that Ann Palmenberg, the world expert in rhinovirus C, was right there within walking distance. So I jogged over to her office. That’s the kind of place this is. It turns out what these chimps had, and this particular isolate was from Betty, was a very typical C45 strain of this virus.

The bottom line is there was nothing special about it. It wasn’t a mutated chimp version of the virus. It wasn’t some strange out of nowhere virus. It’s just the sort of thing that you would find circulating in kids in the hospitals here in Wisconsin during cold season. So why in the world was this happening? Again, due to the expertise of my collaborators, like Ann Palmenberg and Jim Gern in the pediatrics department, we happen to know quite a bit about how this virus latches on to hosts. This is actually an atomic structure, that’s how detailed we can get these days, of the binding complex of rhinovirus C and its host cell receptor. And I don’t understand this either, but what I do know is that we know the receptor quite well. It’s called CDHR3, and what we know about this receptor is that it’s critical for human health. There are two versions of it. The most common version actually resists infection with rhinovirus C and other infectious agents in people, but if you have this rare version, if you’re a person, called the risk allele with a single amino acid change at a single position of the protein, you’re highly susceptible to rhinovirus C infection, and interestingly, you have a 10-fold increased risk of having asthma.

So if anyone’s ever done 23andMe, it’s one of the most informative loci in 23andMe because most people who have asthma will realize they have this variant CDHR3 locus, allele rather. So what we did is we genotyped the chimps at this field site in Uganda and we looked at chimpanzee genomes from across Africa, and we found that every single one of those chimps had the allele of this gene that makes people highly susceptible to the virus and highly susceptible to asthma. The basic idea here is that we have evolved with viruses like rhinovirus C and we have adapted to them, genetically in this case whereas chimps have not. They’ve only recently been exposed to these common cold pediatric viruses of people, and they’re exquisitely susceptible. So all chimpanzees everywhere are genetically susceptible to rhinovirus C infection, and as it turns out, to a suite of other human respiratory pathogens. This concept is actually called reverse zoonoses. I think most people here have heard of zoonoses, diseases that go from animals to people, but it’s not as well-known that there are plenty of diseases that go from people to animals, and they present a global threat to domestic animals and wildlife, and there have been a few papers written about this. I wish I had more time to tell you all the interesting facts about this particular outbreak, but one thing I can’t really tell you yet is how this happens. We don’t know exactly how these viruses get from people to chimps. There are plausible mechanisms.

There are tourists who visit these sites, people like me, people in local villages. Chimps will sometimes leave the forest to go raid crops and they’ll come into close contact with people and the places where they live. So there’s all these different possible ways and we’re looking at that now, but I wanted to start the talk with this story to kind of reinforce the idea that infectious diseases don’t care which direction they go in. We’re concerned about human health because we’re humans, but they’re just as happy to go in the other direction. And they’re just as happy to go to other places like Wisconsin. So this is a group of nine photos that the USGS puts out on emerging diseases in wildlife, and we have six of the nine in our state. So we are not by any means shielded from this phenomenon. I think a lot of people in Wisconsin are aware of a few of them. The two big ones being Lyme disease and chronic wasting disease. So Lyme disease, of course, is a huge problem here.

We’re a real epicenter for Borrelia burgdorferi, the bacterium that causes Lyme disease that is transmitted by ticks, and in fact, we have a Midwest Center of Excellence in Vector-Borne Disease here funded by the CDC that specializes in Lyme disease. Chronic wasting disease, we don’t know if it’s zoonotic yet, but it certainly is emerging, and we’re certainly aware of the spread of chronic wasting disease among the deer herd of Wisconsin. It’s also a disease of major concern, but these two diseases that get a lot of popular press are not the only ones in Wisconsin. So I wanna go through a few other ones that you may not have heard of, starting with a disease of fish. One of the reasons I moved to Wisconsin was because I like to fish. So when this disease popped on to the scene, I became very interested in studying it. It’s called viral hemorrhagic septicemia, and it’s actually caused by an invasive species, an invasive virus. If you do go fishing, you might see these signs posted at the rivers that the DNR puts out to inform people about it. But it started out as a disease that was popping up in association with fish kills in Lake Michigan and Lake Winnebago in the early 2000s, and this was a big issue because fishing is a huge industry in Wisconsin. It’s responsible for $2.3 billion of annual economic impact, and we are third behind Florida and Michigan in the number of nonresident anglers who buy fishing licenses in the United States. So that’s everybody from Chicago coming up in the summer on the weekends. And we catch and keep a lot of fish. And this virus came in 2003 to the Great Lakes region and started causing massive fish kills in a number of fish species, and it turned into a major regulatory issue. It shut down, for a while, the interstate transport of bait fish. So there is a thriving bait fish industry in Wisconsin and surrounding states, and USDA came down and shut that down. Believe it or not, it’s related to rabies virus. So fish get rabies-like viruses too. Rhabdoviruses are all over the place. And it causes this hemorrhagic disease and massive fish kill.

So some people in my lab joke that we should be calling it Fishbola. [audience laughing] It’s like that. The first thing we did with this virus, that’s me trying not to get seasick on Lake Winnebago, was to develop a test for the virus because before we did this, it was impossible to test for this virus without killing the fish. We developed a blood test that you can take a blood sample and then test it for antibodies. And what was interesting is when we applied this test to Lake Winnebago, sort of the ground zero of viral hemorrhagic septicemia in Wisconsin, we were able to show that the virus persisted even when there were no fish kills, that it sort of hung out at low levels in the lake from year to year, even when we were seeing nothing on the surface of the water. Now, you don’t know what’s going on under the water, but we found lots of fish with antibodies to the virus, and the antibodies were going up and going down, and we even found one fish, Typhoid Fish Mary, who is a 24-year-old freshwater drum collected in 2012 that was positive for antibodies and had active live virus in the tissues, in spleen and kidneys. So this was a carrier fish that was swimming around Lake Winnebago, ready to see the next epidemic. What we’re doing right now, and I don’t have results for you yet, is to go around the state with the DNR and test these four species of game fish from the water bodies shown here and in Michigan, where there’ve been several kills caused by this virus, and we’re hoping to map the distribution of this emerging pathogen in the state of Wisconsin. But what we realized when traveling around the state of Wisconsin is that we would encounter fish kills or stories about fish kills or reports of fish kills to the DNR that were not viral hemorrhagic septicemia and were just stuck on the shelf because they couldn’t figure out what they were. So we launched a side project informed by some of the chimp work I’d been doing, that I like to call the Bass-O-Matic Project for those of you who remember the old SNL skit.

So basically, find a fish, grind a fish, sequence a fish, and figure out what pathogens are in it. And guess what? We have been finding loads of new, undiscovered viruses in the fish of Wisconsin. For example, largemouth bass reovirus, which we published a couple of years ago, which is a divergent virus, again, new to science, that’s most closely related to a pretty serious viral disease of farmed salmon, but it’d never been found in a bass before, let alone in Wisconsin. This thing is known from the Pacific Northwest and Norway. So that was surprising, and we’re working on other viruses, like a virus of brown trout that popped up and a virus from some private hatcheries around the state that’s actually related to really nasty human pathogens with names like Crimean-Congo hemorrhagic fever. So we don’t know what these things are doing, and fish, have fun, eat fish, that’s fine, but it’s surprising when you start to look, just how much you find, especially in cases like this where you have animals dying of unknown causes. And that’s really important for people in Wisconsin because we love our animals. At the School of Veterinary Medicine, I think we have somebody studying the health of every one of these animals except for trilobites because they’re extinct. [audience chuckling] We are a state that loves the outdoors. We are a state the loves our wildlife, our pets, and our livestock.

So these things are upsetting to us. They strike not only at the health of our animals, but sort of at our core values as residents of Wisconsin. Not on this poster is one of the most iconic of species around here, the bald eagle. Isn’t that a great shot? [audience murmuring] That went viral. So the bald eagle is obviously an iconic species of bird. It’s important I think to realize that the Founding Fathers did not discover the magnificence of the bald eagle. It was revered by Native American cultures for millennia prior to the arrival of Europeans on North America, but it was chosen as the symbol of United States of America by the second Continental Congress in 1782, and it appears on the Great Seal of the United States. Now, I’d like to address and dispel a myth. Benjamin Franklin did not want the turkey to be the national bird of the United States as some people have said. This is indeed an urban legend that that would have been our seal if he had. [audience laughing]

But Benjamin Franklin did not like the choice of the bald eagle. That is true. He wrote about that because this is how we think of bald eagles, as these magnificent hunters of the sky who fish and swoop down and are majestic. But they’re actually dirty thieves. They engage in this behavior that’s called kleptoparasitism or sometimes piracy, where they mostly make a living by stealing food from other species. In this case, a fox has been lucky enough to catch a nice rabbit and here comes the eagle, swoops down, grabs the rabbit, and the fox is going crazy because he just stole dinner. So bald eagles are notorious for this behavior, which made Benjamin Franklin not like them, and he actually called them a bird of bad moral character [audience laughing] because they don’t make an honest living. So he was quite the natural historian. So a little history on the bald eagle in our country and of course, if we’re gonna talk about bald eagles in the United States, we can’t forget Rachel Carson and “Silent Spring,” where she exposed the deleterious effect of DDT on eggshells and because of this chemical and other challenges, bald eagles, at one point, were reduced in the lower 48 states to only about 400 breeding pairs. They’ve since rebounded to 16,000 or more since last count.

So this is a Fish and Wildlife Service timeline of the path to recovery for bald eagles. It started before Rachel Carson, but really her writings inspired the public to take serious action, and through a series of legislative changes and enforcement, bald eagles were brought back from the brink of extinction. That is the same for Wisconsin as everywhere. 25 years ago, that was the distribution of breeding pairs of bald eagles in Wisconsin. In 2017, it was that, and it’s even higher today. So we are awash with eagles which is great, but eagles are not without threats. So there are lots of things that kill eagles these days. This is from a nice publication out of the National Wildlife Health Center here in Madison, which shows that many eagles suffer poisoning, if they scavenge carcasses that maybe farmers will leave out to poison carnivores, trauma, this is if they’re hungry and they’re by the side of a road, they might get hit by a car, electrocution, landing on electric wires, like that poor eagle there. People still shoot them for reasons I don’t understand, and some of them just don’t make it because there’s natural selection out there and they’ll starve each winter because they haven’t learned how to hunt properly. Among infectious diseases, we really don’t know very much about eagle infections.

There’ve been scattered reports of different infectious diseases that have afflicted eagles over the years. A case here, a case there. The exception to that is West Nile virus, which we know when it arrived in 1999 in the U. S. , did take a toll on bald eagles, and in fact, they’re exquisitely susceptible. This is a paper by my colleague Hon Ip on the right there at the National Wildlife Health Center who showed that bald eagles in Utah were actually getting infected with West Nile virus not by mosquitoes, which is how the West Nile is usually transmitted, but by eating infected eared grebes. So they’re so susceptible, they can get it by eating another infected species. So that’s the one we knew about. Ron Seely, in 2005, wrote this brief report in the “Wisconsin State Journal” about this strange syndrome of bald eagles that had baffled scientists. I don’t know, I’ve never felt more baffled than when I became a scientist.

It’s what journalists like to say, “such and such baffled scientists. ” Well, we were baffled for awhile. But there was this syndrome that’d been noticed for decades in Wisconsin called Wisconsin River Eagle Syndrome. Eagles had been dying mysterious deaths. They would be okay one day and then they would just go into seizures and vomit and be deathly ill the next day and die. And it only seems to happen along the Lower Wisconsin river way. So Wisconsin River Eagle Syndrome. My colleagues at the DNR and the Wildlife Health Center looked at all the things you might expect: every toxin under the sun, all the known infections. Couldn’t find a thing. The images on the right are what a typical liver looks like under a microscope from an eagle that has died of Wisconsin River Eagle Syndrome.

These are kind of nonspecific changes, but these big vacuoles, these holes in the liver cells are what you would typically see in this case, although they couldn’t really figure out what was causing it. So I guess when you’ve got a hammer, everything looks like a nail. We decided to take this one off the shelf and see if we could shed some light on it using metagenomic diagnostics. In other words, take the tissues from these sick birds, put them through our fancy DNA sequencing apparatus, and let the computer tell us what in there was not a bald eagle. We did that, and came out with a really surprising finding. We discovered a new virus that we have called bald eagle hepacivirus. It’s shown there on the right with the eagle soaring off the screen. It is part of a group of viruses that contain two genera, pegivirus and hepacivirus. You probably have never heard of the pegiviruses before. They don’t really cause disease, but you probably have heard of the hepaciviruses because that is the genus that contains human hepatitis C virus, which was interesting because the end stage of infection with hepatitis C virus looks very much like what those eagle livers looked like.

So we had a relative of human hepatitis C in a bird that nobody had any idea it would be. And just about the same time, there’s a group from China that published a similar virus in domestic ducks, but it wasn’t clear what it was doing. So we found this very interesting, very suspicious virus in bald eagles in Wisconsin. And we kind of went crazy with analyses because we’re trying to understand it. What this graph is showing is we constructed a phylogenetic tree or a family tree of eagles themselves because we had their livers and we could do molecular phylogenetics on the birds, and the viruses that were infecting each of those birds on the right. And we tried to say, “Okay, are these family trees matching up at all?” And the answer is no. So we thought maybe that this was some virus that was being transmitted from mother to offspring or father to offspring, vertically transmitted from eagle to eagle and was just sitting there in the eagles. That doesn’t seem to be the case. This argues against that and suggests they’re getting it in some other way. So we looked across the coterminous United States from Florida to Washington State, which is where we found these viruses in eagles.

And we tried to ask, “Well, is there any effect “of geographic distance on the genetics “of the eagles or their viruses?” In the case of the eagles, it’s clearly no. Eagles are eagles are eagles genetically no matter where they’re from, which isn’t particularly surprising ’cause there were only 400 pairs of them back in the 1960s. So they went through a severe population bottleneck. You wouldn’t expect a lot of genetic diversity. But the viruses showed a very different pattern. The viruses from those same eagles clustered into tight little groups, and the farther apart in space they were, the more different they were genetically. It’s called isolation by distance. So what we think is going on is that the virus is being maintained through local cycles of transmission. And it is not necessarily being carried around by eagles. So basically, we don’t know how this virus is being transmitted, but it’s decoupled in a way from its hosts.

What this graphic shows is a bit of the epidemiology and what still makes this very suspicious. It turns out, we found this virus in eagles all over the United States, so not just in Wisconsin, but eagles from Wisconsin were nine times more likely to harbor this virus than eagles from anywhere else. And if we only counted eagles from counties where Wisconsin River Eagle Syndrome had ever been diagnosed, there were 14 times more likely to have been infected with bald eagle hepacivirus than eagles from elsewhere. So where we are right now is sort of in the murky waters of emerging infectious disease. We found an interesting virus in an interesting species, infected or suffering an interesting disease, but we are moving towards testing the idea that this is actually the cause or not. It could be the cause, it could be an incidental finding, but a very interesting virus in an iconic species. And I didn’t realize until I had done this work and it was published, just how popular eagles are, because this went viral a little bit. It got covered all over the popular press. I think I was unprepared for it because as a scientific finding, it was not definitive. It was suggestive and interesting to me and to virologists and ornithologists, but the popular press really picked up on it and I think the reason for that, as you can imagine, is that we love our eagles.

They are deeply ingrained in the national psyche. They’re all-American and here in Wisconsin, they are part of our own iconography as well. So everybody loves eagles is what I learned. So getting back to the broader question here, emerging infectious diseases. I don’t wanna give you the impression that all emerging infections or all new infections are viruses. These days, listening to stories about Wuhan coronavirus, you would think so or Ebola, but they’re not. There are some weird ones out there. So I wanna return to my roots a little bit and talk about apes in Wisconsin. Yes, there are apes in Wisconsin at zoos. So this was an interesting case that came about a little earlier than what I just talked about with the eagles, involving an orangutan at the Milwaukee County Zoo, named Mahal.

I don’t know if anybody remembers this particular orangutan, but it was a great story. He was born in Colorado at the Cheyenne Mountain Zoo and he was rejected by his birth mother. This happens sometimes. We don’t know exactly why, but he was actually flown on a private jet from Colorado to Milwaukee and introduced to his surrogate mom, who took to him right away and raised him like her own, and was this wonderful story of hope and redemption and second chances, and they even wrote a children’s book about it, “Little Mahal and the Big Search for a Real Mom”. It doesn’t get more heart-wrenching than that. And he died suddenly and unexpectedly at five and a half years old, and all we knew was that it was a severe acute respiratory disease of unknown cause. These are, again, for some reason I’m on livers today, but this is Mahal’s liver showing these cysts, which are not normal, and inside some of the cysts, these cells that are not orangutan cells. They’re some other thing that has infected him. And try as the zoo vets might, they could not figure out under the microscope what this was. They sent it around the world to experts in parasitology and fungi and all these different things.

So, I got a call from Annette Gendron, my colleague who recently retired, could this be an obscure primate pathogen called hepatocystis which makes cysts in the liver, hepatocystis, liver cysts, which I had been studying in Africa at that same site I told you about with the chimps. So I told her, “Well, it could be, “so lemme run a quick test and I’ll give you the answer, “and I’ll be home by dinner and you can say what’s going on. ” Never say that, [audience laughing] because I ran the test and it was negative, but I’d already shot my mouth off and told Annette and the folks at the Milwaukee County Zoo that I was going to solve the case. So I was left, for those of you who do infectious disease work, with a very unenviable list of differential diagnoses, basically anything with a nucleus. [audience laughing] So this was in the early days, but we adopted this technology that I’ve told you about a few times now for pathogen hunting, where we took Mahal’s tissues and put them on the machine and said, “Okay machine, tell us what is not orangutan. ” Most of it was orangutan, 97%, but seven of the sequences that we got off of the machine that were not orangutan actually matched Taenia solium, which is the pork tapeworm. Now, Mahal did not have the pork tapeworm. But it allowed us to zero in on this particular branch of the tapeworm evolutionary tree, the Taeniidae which contained, at the time, two genera, Taenia and Echinococcus, which anyone in veterinary medicine will be intimately familiar with. So that was enough information to let us design more specific tests and figure out, did Mahal die of Taenia or Echinococcus? And the answer was no, neither because we found Mahal’s tapeworm to be something in between the two that I show here clustering with this thing I’ve abbreviated V. Right at the time we were doing this, we saw in the literature a publication proposing a new genus of Taenia tapeworm called Versteria, named after Anna Verster, a famous South African tapeworm biologist.

You learn these things. And it turned out we had stumbled on the first primate infection with a tapeworm of the genus Versteria, which was really fascinating. So we had no idea Versteria was in Wisconsin, and we happened to find it in an orangutan in Milwaukee. Doesn’t get any weirder than that. Can’t make this stuff up. So what actually happened? It’s a little confusing because when I say tapeworm, you think of the long tapey thing or maybe you’ve seen these in your cat or dog’s poop and you run screaming to the vet. So this type of tapeworm, in a normal situation, that long tapewormy thing lives inside the intestines of a dog or a cat or a carnivore. And they deposit that onto the environment through these little packets of eggs called proglottids, which then release the eggs into the soil and along comes a mouse and picks those up off of the soil, eats them, and those go into the tissues of a mouse and just wait. And maybe they’ll even slow the mouse down a little bit. And then they just wait for a cat to eat that mouse, and then those eggs hatch inside the cat and migrate to the gut and become the long tapey thing again.

That’s a tapeworm lifecycle. What had happened in the case of Mahal the orangutan is he inadvertently played the role of the mouse. This can happen sometimes. It’s called cysticercosis, where an animal will ingest the eggs and the eggs will hatch, and kinda not know where they are. They know they’re in some animal, but it’s the wrong animal, so they grow out of control and they forms cysts, and they can grow out of control and kill animals. This can happen in many species, but Mahal loved to eat dirt, as any good orangutan does, because it helps with the digestion, and he must’ve picked this up from the soil. So we conducted a two-year investigation into the origins of this thing by going all over the United States to places where trappers and hunters and pest control people were collecting weasels because in Europe, the closest relative of this thing lives in weasels, and we dissected so many weasels. And we wound up finding a few adult specimens of this worm, showing that this genus does in fact live in weasels. We found one in an ermine from Wisconsin, which got us very excited, in Horicon Marsh actually. But that particular one was not very closely related to the variant that killed Mahal.

But a colleague of mine in Colorado at the Denver Museum gave us an ermine that had one of these tapeworms that was an almost identical match to the one that killed Mahal the orangutan in Milwaukee. And what’s really interesting about that is if you recall, Mahal was born in Colorado and flew on the private jet to Milwaukee. So we think that Mahal picked this thing up in Colorado by eating the eggs of a tapeworm from an ermine, and flew with the quiescent infection on a private jet to Milwaukee, where for some reason, five years later, it started to grow out of control and killed him. So this is the lesson for emerging infectious diseases. The ways they get around are virtually unpredictable. I should say that I’m very proud of this study because in both of our publications, we said at the end, “Hey, orangutans are not very different from people. “We should really be paying attention “to this as a possible zoonotic agent. ” And last year, three papers came out based on our results showing that it can affect humans. We predicted it. So one in a kidney transplant recipient, another in a historic case, and a third in a woman from Pennsylvania who reported spending a lot of time with fishers.

I don’t know what she was doing. I think she may have a been a wildlife rehabilitator, but it turns out that in elderly and immunocompromised people these abhorrent infections can happen, if you come into close contact with a definitive host. So we predicted a novel zoonotic agent before it entered humans. And I guess it’s for that type of reason that I’ve developed sort of a street reputation around here for being a disease detective. It’s a very flattering way of saying epidemiologist, so thank you On Wisconsin magazine for doing this. [audience chuckling] But I guess when one has that label, you’re sort of expected to say something about why everybody fears these things, which is pandemics. It’s fine, it’s not fine, but it’s not the worst thing in the world if one animal in one corner of Wisconsin gets one strange disease. But if it starts to spread around the world and threaten global trade and global human health like the pandemic going on right now, then we worry. And a question I get very often is, “Should we here, “in the frozen tundra of Wisconsin, worry?” And the answer is yes we should, because we are by no means isolated. We get these things every year with the flu.

Flu breaks out in Wisconsin like clockwork every year. Most years it is simply the seasonal flu, which is really a term for the mild form of a pandemic because it’s coming from Asia. Some years it’s more severe, in which case we call it pandemic flu, but it is a globally-spreading disease. And then we have weird ones that hit people here in Wisconsin, like you may remember in 2003, the monkeypox outbreak. That was, again, how can you predict this? Gambian giant rats imported to Texas from Ghana carried monkeypox and were sent in a shipment of pets to Indiana and then to Wisconsin, where it made people sick. So a virus from the rainforest of Africa infecting people in Wisconsin through the global pet trade, through a Gambian giant rat. I mean, it’s just very hard to predict these things. What we do know is that this happens often these days because of global transportation. Globalization is a fact of life for us. You can’t even see the U. S., let alone Wisconsin, in that blob of red. This represents connections among airports. So it’s not surprising things can get around. What are some of the other ways that these things might be able to get around and to Wisconsin? Well, this is a tick, and what’s remarkable about it isn’t that it’s a tick or that it’s a tick of the genus Amblyomma, but where it was discovered. I don’t know if anyone remembers this. This one was discovered inside my nose. [audience laughing] This is the famous Ugandan nostril tick. So about ten years ago, eight years ago I guess, this was my claim to fame. No matter what I do in my career from now on, on my tombstone it’s gonna say “Here lies the nose tick guy,” [audience laughing] ’cause I came back with this thing in my nose.

I’d had a few of them before. They’re not uncommon in Uganda where I work, but of course no one’s heard of them here. I pulled it out and I sent it to a colleague of mine at Texas A&M who’s a tick expert, Sarah Hamer, and she sequenced it, and the sequences were in no known database. So what I had in my nose was a new species of tick, or an old species that had never been sequenced. We’re still not sure, but it was a nostril tick, and this went viral. [audience laughing] I had a full-page spread in “The Guardian”. I was in “National Geographic”, “Science”. Twice, I was on “Lightning Fill In The Blank” as a quiz question answer. That was perhaps the greatest of honors. But yeah, this was my 15 minutes of fame because it was completely gross, and a scientist came back to Wisconsin with a tick in his nose.

But what the press missed and I thought was the most interesting part of it was just why did I have a tick in my nose? With the help of some of my collaborators in this forest I told you about at the beginning where the chimps were dying of respiratory disease, there was a study going on to measure the age at which the molars of chimpanzees erupt because as anyone with kids knows, molar eruption when they start to teethe is an important moment in growing up. So how do you do that in wild chimps? You wait for them to yawn and you take a picture of their face. 99% of the time, you miss ’em. They’re looking away or their mouths are closed. So what we had was this gigantic photo archive of baby chimp faces. And we looked through them and found that about 20% of them had ticks in their nose. So you can see them here inside the nostrils, up in there of these four chimps and many more. So what I had in my nose was a chimp tick. And for anyone who knows about chimps, this will make perfect sense because what do they love to do to bond their societies? They groom each other. So if you’re a tick out in the open on a chimp, you’re dead meat ’cause you’re gonna get groomed off and eaten.

So you have to find a place to hide. There’s a few places you could think of, but the nose is a really good one because it’s warm, it’s wet, it’s vascular. So if you can get in there, it’s great. And I’m pretty much a chimp with language. So the tick didn’t care. [audience laughing] It got into my nose, flew on a trans-Atlantic flight back to Madison where I discovered it. Now, as far as I know I haven’t sparked any pandemics, but it’s a nice example of how globalization comes home. And I should just mention because I love these types of stories. This is an evolution story. Chimp nose ticks are not the only things that do this.

This is the chimp louse, Pediculus schaeffi. It’s unique among lice because if you shine a flashlight onto it, it will let go of whatever it’s holding on to and drop to the ground, which is suicide if you’re a louse. But if you think about it, if you’re a louse on a chimp and another chimp parts the hair to groom and the light shines on you, you better jump chimp and find a new chimp, or else you’re gonna get eaten. So, this is– in the School of Veterinary Medicine, as on this campus, there are researchers who are wonderful at studying all the intricacies of how viruses evade the cellular and humoral immunity of their hosts through these complicated biochemical pathways and strange mechanisms. Parasites do this too, but behaviorally. They have adaptations like the microbes inside us to avoid host defenses. So I just like that story because it’s another example of an evolutionary arms race with host and pathogen. So my intent here partially was to scare you by letting you know [audience laughing] that yes we really do have to worry about emerging infectious diseases, and there are more and more of them every year. I guarantee you that Wuhan coronavirus will not be the last of the emerging infectious diseases that any of us see. These things are happening all over the place, and I often get asked, “So what are you doing about it?” So I’ll just hit very quickly on the fact that there are interventions being designed.

You may have heard in the news that scientists are rushing to develop a vaccine. That’s great, but that’s not an outbreak response. That vaccine will be ready for the next outbreak. So the honest truth is that there are no magic bullet solutions for halting pandemics in their tracks. Once they’ve started, they keep going. So it’s one of the unfortunate aspects of being an epidemiologist that when you do your job, nobody notices, because if you prevent an epidemic or prevent a pandemic, how does anyone know? It’s only when something breaks out that people say, “Well, you should be doing your job. ” Well, I prevented seven pandemics last week, what do you expect of me? [audience laughing] But what we do in between epidemics and phone calls from the press about strange viruses is we try to do sort of basic public health interventions, things like education. In Uganda, we have a new project called Healthy Children, Healthy Chimps or HC Squared, where we’re trying to examine how these pediatric viruses are getting out of the children into the chimps, and at the same time, use it as an avenue for educating kids and their families about basic health, basic healthcare and basic health prevention. And for some of the emerging pathogens in Wisconsin, all I can say is that I’m working with the various agencies in Wisconsin that have established programs on interacting with the public. We can do things.

We can do things like set management zones or put up signage or change the way we monitor. So none of it is like a vaccine that’s gonna save everybody tomorrow. It’s not like the movies. This is kind of hard, slogging public health that happens at a slow pace without necessarily the fanciest technologies. So I will stop there except to say that all these projects are big projects of which I’m only a part, and I’m grateful to all the collaborators and funders who have helped over the years, and I would be, of course, happy to stop and take any questions. [audience applauding]