Bent Out Of Shape: Could A Mysterious Animal Epidemic Become The Next Mad Cow?

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Originally published on April 22, 2019 10:39 am

Chronic wasting disease is crippling deer populations in the Mountain West, around the country and in bordering Canadian provinces. It's not a bacterium or a virus or even a fungus, but caused by something called a prion, a type of protein that all mammals have in their bodies.

From the Mountain West News Bureau and published in collaboration with High Country News, this four-part special report examines the disease's origins and impact, and a global effort to stop it from spreading.

Part 1: A Mysterious Animal Epidemic

Heather Swanson and Ryan Prioreschi monitor wildlife with the City of Boulder. They're standing in knee-high golden grass on a slope where the Rocky Mountains start slumping into the plains — the epicenter of a now-international animal epidemic. The ecologists have their binoculars out and they’re staring right at the problem.

A fawn is running circles around the rest of the herd, with the boing of a muscular slinky toy.

"He's wired," says Swanson, laughing. "He's doing laps."

A few others are rearing up on their hind legs and kicking each other. The rest of the herd of mule deer are just hanging out in the shade. It looks like a beautiful spring morning and the animals look sleek and healthy. But all is not what it seems.

"That is buck number 46," says Prioreschi, pointing to a deer. "He is positive."

Doe number 22, currently laying in the grass, is also positive for chronic wasting disease.

"Doesn't show any symptoms. She looks perfectly fine," says Prioreschi.

The mountain lions know that something is wrong. A number of years ago, Swanson and her colleagues studied which deer mountain lions prefer to attack.

"The mountain lions were definitely preferentially selecting deer that had chronic wasting disease over those that were negative," she says. "And for most of the ones that they had killed, we had not detected any chronic wasting disease symptoms yet. So certainly the lions were able to key in on far more subtle cues than we were."

Unlike us, the lions know that while a deer might look sleek and alert, it's actually a ticking time bomb. That's one of the weird things about this disease. It isn't like the usual viral or bacterial illness. The infection can sit in a herd, crawling from animal to animal, for years before people notice anything is wrong.

"Through time (it) degrades, essentially, their brain tissue," says Swanson.

Then, things can go downhill fast. Swanson says it could be a matter of weeks before buck 46 or doe 22 starts to droop and drool, as an infection gnaws holes into its brain.

"That seems to happen pretty rapidly," she says. "To our eyes they look fairly healthy and within a number of weeks they reach that point and then they're gone."

Scientists have called chronic wasting disease a nightmare and a state of emergency. Lawmakers are calling it a crisis. Lately, the media’s been calling it "zombie deer disease." There are at least three bills being considered at the national level right now to combat the disease.

A few weeks ago, Wyoming Senator John Barrasso got in front of a congressional hearing to introduce one of them.

"Today I'm here to talk about a different kind of health crisis that's facing our nation," said Barrasso.

The neurodegenerative disease infects deer, elk and moose.

"It's highly contagious and always fatal," said Barrasso. "Unchecked, this disease could truly be catastrophic for wildlife and for local economies."

Barrasso's bipartisan bill is cosponsored by senators from across the country, including Idaho, Wyoming and Colorado. It would give federal dollars to the National Academies of Sciences to identify major gaps in scientific understanding of CWD and to better identify how to keep the disease from spreading further among animals, including from those in Canada to the U.S.

On the same day that Barrasso addressed his colleagues in Congress, epidemiologist Michael Osterholm spoke to state lawmakers in Minnesota.  

"This is kind of a worst-case nightmare," said Osterholm.

It's a nightmare that's hard to explain. Chronic wasting disease is not your garden variety infectious disease. It's not bacterial, viral or even fungal. It's caused by something we all have inside our bodies — something called prions.

As Osterholm put it to Minnesota lawmakers, "If Stephen King could write an infectious disease novel, he'd write it about prions."

Osterholm might not be far from the truth with his sci-fi reference. A book by Kurt Vonnegut, Cat's Cradle, comes up a lot in reference to prions. In it, there's a fictional substance called Ice Nine, a strange form of water that is solid at room temperature. When it touches liquid water, it turns the liquid to ice, too. That's very close to how prions cause disease.

"They're just very different from traditional pathogens," said Kaitlyn Wagner, who researches prions at Colorado State University. She says the prions that cause chronic wasting disease start out as normal proteins. All mammals have normal prions, sitting on the surfaces of our healthy cells. The difference between a good prion and a bad one is the shape.

Mark Zabel, who is associate director of the Prion Research Center at Colorado State University, says one way to think about it is origami. Healthy proteins are shaped like origami cranes. If an abnormal origami crane comes along with a bent wing, the normal origami cranes will start to copy it. One by one, their wings will bend as well.

Eventually, when a badly folded prion has, as Zabel puts it, "coerced" enough healthy proteins to get bent out of shape, they can gather in clumps, killing off cells and leaving the brain full of holes like a sponge.

In the case of other prion diseases, including bovine spongiform encephalopathy — also known as mad cow disease — the badly folded proteins tend to stay contained in the brain and nervous system, but animals infected with chronic wasting disease leave behind infectious proteins all over the place. They've been found in urine, feces, blood and saliva. And those misshapen proteins can stick around.  

Zabel says a virus might be able to survive for a few hours outside its host. A bacterium might be able to make it for a week or two. A prion, on the other hand, would be capable of sticking around for years — decades, even.  

To complicate things, studies have shown that plants can suck them up through their roots and harbor them in their leaves, potentially infecting the next animal that comes around for a snack.

There's a lot that’s still unknown. What researchers do know is that it was first identified in Colorado way back in the 1960s and now chronic wasting disease has crawled its way across the country, infecting deer, elk and moose in at least 26 U.S. states and three Canadian provinces.  It's also turned up in South Korea, Finland, Sweden and Norway.

And it all started here, in the Mountain West. Or did it?

Part 2: An Animal Epidemic Goes Global


The question of where chronic wasting disease came from reopened in the spring of 2016.

Roy Andersen was monitoring reindeer in Norway. He’s a research technician with the Norwegian Institute for Nature Research.  On a rare, sunny day, Andersen and his colleagues were doing what they often do in the spring: blasting across a snowy plateau, chasing a herd of about 500 wild reindeer.

Reindeer are big and fast and skittish, so the researchers don’t mess around. They dart them with tranquilizers from a helicopter.

"Everything is going really fast, of course. They're running quite fast," he said.

The group's veterinarian was hanging out the side of the helicopter, dart gun in hand. Andersen says he shot one dart and missed, then tried again.

"And he also missed on that dart, too, so that's when we had to stop," he said.

They landed the helicopter. Andersen and the others got out to track down the darts. The copilots were waiting by the helicopter when one of them spotted something.

"He mentioned that he saw something down the hill about 200 meters away," said Andersen, who decided to take a look.

It was a reindeer.

"It was lying on the side, flat out — not very common for reindeer. And it had all these bubbles and stuff coming out of his mouth,"” he said.

Three or four minutes later, it was dead. Andersen and his colleagues thought they had accidentally killed it — that maybe a dart had hit it in a weird way, or that it was just stressed out from the helicopter chase. So they zipped it up in a giant duffel bag.

"And we brought the animal with us down from the mountains to find out what had happened to it," said Andersen.

Samples from the sick reindeer eventually made their way over to the laboratory of Sylvie Benestad with the Norwegian Veterinary Institute.

"And it was really strongly positive," she said — positive for chronic wasting disease. "That started the problem."

Benestad says Norway has some of the only wild reindeer in Europe. If it spread to semi-domesticated reindeer, it could cause a cultural crisis.

"We are all aware of the threat if CWD spreads to semi-domesticated reindeers. It could easily wipe out the entire Sami reindeer husbandry culture," said Randi Skum with the Sami Reindeer Herders' Association of Norway.

Based on how it quickly and viciously it spread in the U.S., the Norwegians knew they had to do something.

"If we didn't do anything, it would be enormous consequences, so we felt that we had to react immediately," she said.

The Norwegians sent sharpshooters out in helicopters and snowmobiles to kill all the reindeer where the infection had been found — about 2,400 of them.

Among those euthanized animals, 19 tested positive for chronic wasting disease. Luckily, Benestad says, the area is fairly isolated, with roads on one side and mountains on another. They built a fence for good measure and started intensive surveillance of animals across the country. It's now forbidden for reindeer herders to gather lichen and plants from certain areas to feed their animals.

Did those control measures work? Call back in ten years, says Benestad, and maybe then she'll have an answer.

"We still don't know how it came to Norway," she said.

Norway has strict rules about importing live animals, so Benestad says CWD couldn't have arrived that way. One hypothesis was that it came from the U.S. way back in the 1930s and '40s when Finland imported white-tailed deer to populate its forests. (Fun fact: all white-tailed deer in Finland are descended from less than 10 American animals.) But that was long ago, and there didn't seem to be any problem with Finnish deer. Maybe, Benestad says, it came from lures made of deer pee, which hunters can buy online.

But then something else happened.

"About two months after the first case in reindeer, we discovered two moose," she said.

Again, Benestad analyzed the samples.

"And I noticed immediately that it was something different," she said. "The brain distribution of this abnormal prion protein was different."

She concluded this version of the disease was not the same as the one circulating in North America. And upon closer inspection, the disease in reindeer was different, too.

Then last year, a moose in neighboring Finland tested positive as well, way over by the Russian border, and in March 2019, the illness showed up in Sweden. A hunter came across a moose that was in bad shape. It was thin and confused, walking in circles.

"The hunter thought that perhaps it was blind," said Maria Noremark, a veterinarian and epidemiologist with the National Veterinary Institute in Sweden. "And that was the first case we have detected in Sweden."

It's worth mentioning something important, though. That moose was 16 years old. The other cases of chronic wasting disease in moose have also occurred in elderly animals. On top of that, the infection shows up in fewer places in the body than it does in deer and reindeer. It also seems to be a lot less contagious than the CWD circulating among deer.

Scientists are trying to figure out what all this means.

Maybe, Benestad and Noremark say, moose are like people in that a certain amount of prion disease will naturally (albeit very rarely) arise in older mammals, and because it’s contained in the brain and spinal cord, there’s very little concern for contagion.

But that doesn't explain the reindeer, which, like deer, seem to experience the disease much younger and in a much more contagious form. Could there be multiple kinds of chronic wasting disease? And where are they coming from, anyway?

"I mean, the first cases in North America also came from somewhere," said Noremark.

Part 3: A Complicated Turn Of Events


Researchers first identified chronic wasting disease way back in the 1960s. Soon after, Michael Miller got sucked into working on it.

"Yeah, sucked into it is really right," he said.

Miller is a senior wildlife veterinarian with Colorado Parks and Wildlife. Back then, local wildlife scientists were studying captive mule deer at a facility in Fort Collins, Colorado. They were trying to figure out how to help mule deer in the wild survive harsh winters, but the animals kept getting sick and dying.

It didn't make any sense. Finally, they looked at pieces of the animals' brains and saw something disturbing: the brains were full of holes, a pattern similar to what happens with mad cow disease. They soon discovered it was hard to kill, too.

"The folks who were running these research operations decided to try to get rid of the disease, so in the mid-80s they gathered up and killed all the captive deer and elk they had and did what, at the time, seemed like a very thorough job of cleaning up the facility grounds," Miller said.

They cleaned the pens where the animals had been kept, turned the soil, brought in a helicopter to drop chlorine onto the site, and left it alone for a full year. Then, they brought in healthy wild elk calves.

"And we failed," said Miller.

With a couple years, the disease was back. Miller and his colleagues worked hard to figure out how to contain it in northern Colorado.

"The idea at the time was that we would do what we needed to here, locally, to keep it from spreading to the Western Slope. What we didn't realize is that it was actually more widespread. It was a really nice idea that was probably 10, 15, maybe 20 years too late," he said.  

Over the next few decades cases kept showing up in new places, first in captive animals, then in the wild. Cases mushroomed across the U.S. and Canada. It even jumped continents, flying from Canada to South Korea in a shipment of infected elk.

Early modeling work hinted at the possibility that chronic wasting disease might make deer go extinct.

"That's probably not going to happen. It's certainly not going to happen any time very soon. What is more likely is that we will have a deer herd that is unable to grow," he said.

A bad winter, for example, could do some real damage to herds if enough animals among them are infected.

People in Canada, the U.S. and Nordic countries are scrambling to keep the disease under control. Idaho is trying to tighten rules about moving animals across its borders. In Wyoming, environmental groups are suing the U.S. Fish and Wildlife Service for feeding elk in the winter, which they believe could contribute to the spread of chronic wasting disease.

Colorado just came out with its latest management plan, which includes testing animals, thinning out overly infected herds in some cases, scoping out the possibility of investing in incinerators to dispose of infected carcasses, and warning hunters and taxidermists about how to handle infectious material.

"We're not talking about going in and annihilating deer over large tracts of land," said Miller about the plan in Colorado, where 57 percent of deer herds and 37 percent of its elk herds are infected. "We've actually done that," he said, adding that it was only once and not on a very big tract of land. "It was under the misguided notion that it had just gotten there, and we could actually stamp it out if we did something quickly. And again, we were wrong."

"It isn't something that lends itself to a quick fix, and we don't need to do draconian things but we need to do something," said Miller.

Historically, a lot of these plans have rested on one big assumption: That the disease started here in the Mountain West and then moved everywhere else. But Mark Zabel, who studies the disease, says that could be wrong in a big way.

"Most of the outbreaks in the U.S. can be traced back to movement of animals on the game farms from the Front Range to places like Saskatchewan in Canada to the Midwest and Wisconsin to South Dakota, repopulation in Arkansas," said Zabel, associate director of the Prion Research Center at Colorado State University. "But then there are some that have no known connection."

For example, scientists were mystified in 2016, when the disease showed up in Norway and then later in Finland and Sweden.

"I think this question of what's going on is kind of opened up again," said Kaitlyn Wagner, a PhD candidate in microbiology at Colorado State University.

Wagner and Zabel have a hypothesis. They think there isn't necessarily one chronic wasting disease, but instead a bunch of different strains of it. Those different strains, they say, could be emerging at different times across the globe.

On a February morning in the lab in Fort Collins, Colorado, Wagner and Zabel are comparing the prions from the brains of CWD-infected deer in Texas and elk in Colorado, as part of a project looking at samples from seven states. They want to know if they're different.

"If they are different, this would suggest that we have different strain properties which is evidence as we're building our case that we might have multiple strains of CWD circulating in the U.S.," said Wagner.

Step one is to see if they're just as easy to destroy using a chemical called guanidine. The shape of a prion dictates everything, including the way it interacts with an animal's cells and the ease with which chemicals can unfold it.

"Moment of truth," said Wagner, as she and Zabel huddled around a computer, waiting for results to come through. When they did, Zabel was surprised.

"Unlike anything we've seen before," he said. "Awesome."

The prions from the Texas deer are a lot harder to destroy than the ones from the Colorado elk. In fact, they're barely damaged at all.

"We've never seen that before in any prion strain, which means that it has a completely different structure than we've ever seen before," said Zabel.

And that suggests it might be a very different kind of chronic wasting disease. The researchers ran the same test on another Texas deer, with the same results.

Now, these are only the preliminary results from a few animals. Wagner and Zabel have a lot more experiments to do. But if future tests come to the same conclusion, it would support their hypothesis that there are multiple strains of chronic wasting disease with different origins. That, in turn, could mean that this disease will be an even trickier challenge to manage than it already is.

And, Zabel adds, there's something else.

"If it's still evolving, it may still evolve into a form that could potentially, eventually affect humans," he said.

It turns out, Zabel is not the only one worried about that possibility.

Part 4: The Next Mad Cow Disease?


Michael Osterholm is worried. He directs the Center for Infectious Disease Research and Policy at the University of Minnesota. He's also serving a one-year stint as a "Science Envoy for Health Security" with the State Department. And he told Minnesota lawmakers that when it comes to chronic wasting disease, we are playing with fire.

"You are going to hear from people that this is not going to be a problem other than a game farm issue. You're going to hear from people that it's not going to transmit to people and I hope they're right, but I wouldn't bet on it," he said. "And if we lose this one and haven’t done all we can do, we will pay a price."

If that wasn't warning enough he added: "Just remember what happened in England."

Decades ago, Osterholm got involved in a newly emerging disease — bovine spongiform encephalopathy, later dubbed "mad cow disease."

"I was included in a group that actually provided an initial assessment to the British government on the potential for the BSE prion to be transmitted on to humans," he said.

At that point, scientists hadn't documented a prion disease in animals that could infect people, but they did have a few pieces of the puzzle. For one, work in Papua New Guinea had showed that people could transmit prion diseases to each other if they practiced cannibalism, especially of the brain-eating variety. They also knew that BSE was spreading quickly between cattle. Osterholm says he and others worried that the more it spread, the more chances the disease might have to change into something that could sicken people.

"A lot of people thought that it was an overreaction," says Osterholm. "Then, of course, in 1996, ten years later, we recognized that in fact transmission had occurred."

Variant Creutzfeldt-Jakob disease, as the illness is called in people, has infected about 230 people worldwide.

Osterholm feels like he's having a deja vu moment, except instead of mad cow, it's chronic wasting disease that's now spreading in animals, with the potential to cross a species barrier and infect humans.

Daniel Schmidt says Osterholm needs to lower the fear flag.

"To say that without any concrete proof — I think that's irrational," said Schmidt, editor-in-chief of Deer & Deer Hunting.

"If CWD is a threat, it is more to the lifestyle of the hunting public in America," said Schmidt. "Because if you scare people enough in America they're going to stop doing something."

Schmidt and his family live in Wisconsin. He says they eat wild venison almost every day and don't give chronic wasting disease a second thought.

If you need something to worry about, he says, how about climate change, or pesticides in your strawberries?

"This is not a zombie apocalypse and the hamster wheel of fear-mongering is nothing short of sensationalism, in my opinion," Schmidt said.

So, who's right? Could chronic wasting disease present a public health crisis? Or are we, as Schmidt put it, merely hamsters spinning the wheel of fear?

The answer to that question largely rests on the shoulders of Stefanie Czub. She's a professor of veterinary medicine with the University of Calgary and she also runs the Canadian Food Inspection Agency lab that tests for mad cow disease. Everyone's waiting for results from her decade-long study of chronic wasting disease in macaque monkeys. It’s actually about to end, in March 2020.

"Which is too bad, because such an experiment will never, ever be repeated," said Czub.

She says the experiment has cost Canadian taxpayers about $8.5 million, paid for primarily by Canadian taxpayers through the Alberta Prion Research Institute. Now, funds are running out. So is support for research on primates.

"At this point, what we would like to stress — my collaborators and I — is that we have some evidence that it might infect non-human primates," said Czub. "However, the project is not completed yet."

Czub and her collaborators took 18 macaque monkeys and exposed them to chronic wasting disease prions. Some had the prions inserted straight into their brains. Some ate infected venison. Others got exposed via blood transfusion. And some were given little cuts, which were then wrapped in infected deer brain, which was meant to model how a hunter might be exposed to infectious material after getting cut during field dressing. There were also three control animals, which received tissue from healthy deer and elk.

Here's what the group has found. So far, four out of the 18 monkeys developed what Czub calls "subtle and transient" symptoms that "could be indicative of a prion disease." Two of them had received CWD straight into their brains. Two had eaten infected meat.

They lost weight and became anxious.

"Anxiety is a very common clinical expression in animal prion diseases," said Czub. "It is one of the main symptoms in bovine spongiform encephalopathy, and that is the reason why some people decided to call it 'mad cow disease.' The animals are not mad, they are scared to death."

She says in monkeys, that involves crouching in the farthest corner of the cage. They would also shiver and have difficulties picking up pieces of food. One monkey lost a third of its body weight in six months.

After the four symptomatic animals were euthanized, Czub and her colleagues ran a bunch of tests, which Czub says "suggested the presence of CWD" and concluded that they did, indeed, have chronic wasting disease. But there are a number of things that make this complicated. First off, three of the four sick monkeys also happened to have diabetes.

"And it's really important to mention that because diabetes — uncontrolled diabetes — really does induce wasting, so we need we need to be super careful in the interpretation of wasting," said Czub.

It's also really important to say that Czub has presented her preliminary results at conferences, but they've never gone through the true scientific wringer: peer-reviewed publication. That's a really important step, because where one researcher might see an unusual level of anxiety, another might just see an animal in captivity. Even results from more technical evaluations, like analyzing slices of the brain for neuron death, could potentially be interpreted in different ways.

"We'd like to see them published so we can get a better idea of how strong the data really is to support transmission," said Brent Race, a staff scientist at Rocky Mountain Laboratories in Montana, which is part of the NIH's National Institute of Allergy and Infectious Diseases. He and his colleagues ran an experiment similar to Czub's.

"Our studies in macaques have been published three different times now," said Race. "We watched our macaque monkeys for over 13 years in some cases and we were unable to find any evidence of transmission of chronic wasting disease."

Their study on "humanized" mice spliced with a human gene also showed no strong proof of transmission. Race and his colleagues tried to make it as easy as possible for the infection to take hold: They used mice that not only had human prion protein, but a lot of it, they injected CWD straight into the animals’ brains, and they also used a very sensitive test to check for signs of disease transmission. Eighty-four out of 88 mice came back negative. The remaining four came back with fuzzy results, which Race is now investigating further.

Race's study on squirrel monkeys, on the other hand, concluded that those animals were highly susceptible to chronic wasting disease. Thirteen squirrel monkeys were exposed to the disease directly in their brains. All of them developed symptoms including severe weight loss, tremors, drooling and weakness after an average of about four years. The researchers fed another group of 12 squirrel monkeys with infected meat and found that 11 of them developed CWD an average of about six years after exposure. Importantly, the researchers wrote in the journal Emerging Infectious Diseases, macaque monkeys are biologically much closer to humans than squirrel monkeys.

"Aside from a few benchtop assays and the unpublished macaque study from Canada, news has been very encouraging," said Race.

A systematic review of 23 studies including Race’s concluded that, "Five epidemiological studies, two studies on macaques and seven studies on humanized transgenic mice provided no evidence to support the possibility of transmission of CWD prions to humans."

However, the review added that the results from the squirrel monkeys — along with a number of test tube studies — muddy the waters. "Therefore, future discovery of CWD transmission to humans cannot be entirely ruled out," the review stated.

Christina Sigursdon, a professor of pathology at UC San Diego and UC Davis, did a study that hunting enthusiasts have pointed to as a reason not to worry about chronic wasting disease.

It showed that a certain part of human prion proteins makes them incompatible with chronic wasting disease prions and so healthy human prions shouldn’t be capable of getting misfolded, kind of like how a zipper just won't zip if the teeth are different sizes.

"So, it suggested that this region was a barrier — at least, a partial barrier — for blocking infection," said Sigurdson.

But only a partial barrier — and even then, only a partial barrier against the particular versions of chronic wasting disease from Colorado that Sigurdson used.

"We need more research to find out how many strains there are, how different are these different strains and would there potentially be some strains in the U.S. that could be infectious for people," she said.

The Centers for Disease Control and Prevention haven't found any evidence of chronic wasting disease in people, despite researchers actively looking for them. Epidemiologists in states like Colorado and Wyoming are also watching for an elevated rate of prion disease in hunters, who would be most at risk from eating venison.

Hunters like researcher Brent Race.

"I'm an avid hunter myself and my entire family eats it," Race said. "Actually, we raise cattle and we sell all of our cattle and eat deer and elk instead."

But Race wouldn't go so far as to eat meat that hasn't been tested for chronic wasting disease. In fact, that's a feeling shared by pretty much every person in this story: If you're hunting in an area with chronic wasting disease, get the animal tested before it ever hits the plate, and don't eat meat that tests positive.

"Otherwise," said Michael Osterholm, "I wish you well and hope you enjoy your venison."

This story was produced by the Mountain West News Bureau, a collaboration between Wyoming Public Media, Boise State Public Radio in Idaho, KUER in Salt Lake City and KRCC and KUNC in Colorado, and published in collaboration with High Country News.

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