BJW
- Jan 27, 2020
- 7 min read

"Zombie Deer" - a footnote

“Weird.” Steph watched the animal through his set of binoculars. “Eh, what’s that?” Steph’s friend turned inquisitively in the hammock, then noticed the object of his attention: a stag of moderate build. He fumbled hastily out of the ensnaring hammock and reached for his rifle. “Buford, something’s off with this one.” Something glistened in the warm afternoon sun on the buck’s snout, a slimy thread of drool. His friend snorted impatiently, fresh venison clearly on his mind. “What, ya think it’s one of them zombie deer?” He cackled crazily and sighted his rifle. The deer seemed to not hear or care about the commotion, its disposition remaining eerily placid. There was a sharp report of a rifle, but deer remained standing. “What the fu-” “You missed.” “Oh.”

As Buford shoved another round into his museum piece of a gun, Steph continued to watch the deer. It was beginning to move in the jerky, uncertain gait of an automaton. It was just about to disappear into the shadows of the forest when a second shot sounded. “I got him.” “Yeah, but you should have gotten him the first shot. I’m going to check this deer out.” Unbidden, Buford crunched off into the undergrowth after his companion, rifle in hand.

[1]

The deer seemed to be in even worse shape closer up. Even if the second round had missed, it didn’t look like it would have made it much longer. It was clearly in the last stages of starvation. “Even if this deer wasn’t sick, there isn’t much to eat anyway.” “Sick with what?” “Only one way to find out. I reckon we should pay a visit to the specimen testing station.”

Two weeks later, a portion of the deer found itself watched again through a different set of lenses. This time, however, the observation took place in the crisp environs of a diagnostic laboratory. The hinges of a lab chair squeaked slightly as the occupying scientist leaned forward to adjust the focus of the optical microscope. “Anything?” Her accompanying intern hovered curiously nearby. “Yes. Almost certainly.” The elder beckoned to her charge. “Come, you may take a look.” The intern shuffled forward, eagerly pressed his eyes against the rubber eyepieces and adjusted the focus for his younger, un-myopic eyes.

Spongiform brain tissue sampled from a CWD-infected deer [1]

After a few perplexed seconds he turned back to his mentor. “What exactly am I looking at?” “Possibly the first case of CWD in Washington state. It’s spreading, it would seem.”

- - -

The above scenario, is of course, a fabricated scenario. As of the latest from the CDC, CWD, or Chronic Wasting Disease, has not been found in Washington state. However, CWD does appear to be spreading.

(left) Distribution of CWD in 2005. States shaded dark gray represent states where CWD has been found in deer farms [2]. (right) Distribution in 2019 [3]

However, as Belay et al. 2004 notes, the discovery of CWD in new states does not necessarily represent a new and recent and spread of the disease, it could also just be the result of tighter surveillance [4]. It’s a somewhat useless and subtle distinction to make for most, but I suppose it’s important if you want to have an accurate idea of just how fast CWD is spreading. Sorry to split hairs, but I thought I’d mention that.

The described symptoms - ataxia (difficulty moving around), lack of awareness, excessive drooling, and emaciation are accurate as well. Patchy retention of winter/summer coat is a secondary symptom due to the malnutrition that results from infection [1,2,4].

This is nice and all, but what the heck’s making those holes?

So we’ve finally arrived at the question of the pathogenic agent. None of the usual suspects are responsible - viruses, bacteria, parasites. CWD is a prion disease, a prion being a misfolded and infectious version of a protein normally found on the exterior of cells. The “normal” prion protein is highly conserved (i.e. found in similar forms) across mammals, where it is implicated in important roles such as immune system, nervous system, and apoptosis regulation [5,6].

Side note: just to be 100% clear here, CWD does not re-animate deer corpses in the literal sense of zombies (duh). Instead, CWD leads to deer exhibiting "zombie-like" behavior.

The infectious form can replicate by interacting with normal prions, inducing them to convert into this misfolded, infectious form. So prions don’t really “replicate” like bacteria and viruses. Instead, they convert already existing protein by “malign influence,” if you will. In this way prions bear strong resemblance to weebs.

[1]

Ok, but how is it doing it?

I used to think that it was this build-up of pathogenic prions that directly caused the striking “spongiform encephalopathy” or sponge-like state of the brain that you saw earlier. However, it does look that there’s some research proving this personal assumption wrong. Briefly, mice that were genetically engineered to only produce free-floating (vs. cell-attached) “normal” prions were infected with pathogenic prions. While infection resulted in clinical manifestations “reminiscent” of Alzheimer’s disease, these were “minimal” and did not seem to involve

spongiform encephalopathy [7]. Thus, it seems like the prion plaques are not directly involved in the mechanism causing this signature clinical manifestation.

What's responsible then?

Kovacs et al. 2008 puts it this way: “The exact mechanism is not clear but is likely a result of abnormal membrane permeability and increased water content within neuronal processes. It may be also result from autophagy [the recycling of cell components]” [8]. So in other words, we still need to find out how prions are connected to this mechanism...

I think I’ll write up a more in depth post about prion biology at a later date, but for now, let’s talk about the most pressing questions.

Can CWD spread? Is it infectious?

There’s a lot of direct and indirect evidence that it can. From what I’ve told you thus far, you might assume that the infectious prions exclusively hang out in the brain. However, this is not the case. CWD prions have been found in the saliva, urine, faeces of infected animals, and even in a water sample taken from a CWD-endemic area [6,9]. It’s also pretty much everywhere in the deer, in tissues such as the heart, spinal cord, tonsils, blood, and skeletal muscle [2]. As it’s been shown that oral exposure is all that is necessary for infection, it’s not too hard to imagine infection occurring via ingestion of contaminated material [2]. To corroborate this theory, Williams et al. 2002 notes that “contaminated pastures appear to have served as sources of some CWD outbreaks” [1]. The implications of this is that once CWD has reached an area, deer in the area are at a constant risk of an infection, even if there are no deer currently infected. This would be due to the degree of environmental resistance possessed by prions, which is probably higher than even anthrax spores, since after all, prions are just proteins. No nucleic acids susceptible to degradation by UV radiation, nothing.

Even worse for the deer, “models...failed to reach steady-state equilibrium in infected deer populations, indicating that CWD may lead to local extinctions of infected deer populations [1]. There is no treatment for CWD, and all infections result in a 100% fatality rate, on average within 23 months [1].

Can humans get CWD?

Time for the million-dollar question. It’s a valid one, as prion diseases have been proven capable of crossing the species barrier. Variant Creutzfeldt-Jakob disease (vCJD) is a prion disease in humans that result from exposure to BSE (bovine spongiform encephalopathy/mad cow disease) prions. There’s been over 200 cases, mostly in the UK, although the feared pandemic has not materialized [6].

[6]

So can humans get CWD or not? The short answer: experimental and “field data” suggest that this isn’t very likely. Early research testing the susceptibility of squirrel monkeys gave pretty frightening results, with the monkeys exhibiting a high level of vulnerability to oral inoculation with CWD prions. However, cynomolgus macaques were shown to be highly resistant to even intracerebral inoculation. As a result, these trials weren’t really regarded as reliable indicators of human susceptibility [10].

Belay et al. 2004 reviewed the “field data” of all cases of human prion disease possibly caused by CWD prion exposure, there were none confirmed. They conclude: “the lack of evidence of a link between CWD transmission and unusual cases of CJD, despite several epidemiologic investigations, and the absence of an increase in CJD incidence in Colorado and Wyoming [CWD endemic states] suggest that the risk, if any, of transmission of CWD to humans is low” [4].

However, the real test came when mice that had been genetically engineered to produce human prions were intracerebrally inoculated with CWD prion, essentially simulating the exposure of a human. Since intracerebral inoculation, or direct exposure of the brain with the prions is the most direct, sure way to initiate infection, this test would more or less conclusively determine human susceptibility.

Brain tissues taken from the exposed genetically modified (or transgenic) mice. Panels a-h show healthy tissue from mice exposed to CWD prion. As a positive control to show what “successful” infection would look like, panels i-j show samples from a mouse infected with BSE prions. The dark dots are sites of prion build-up. [9]

As you can see from the figure above, the genetically modified mice failed to develop signs of disease. However, before you celebrate by biting into your venison sandwich, Sandberg et al. issues one caveat: it seems there are multiple “strains” of prions. The good scientist cautions: “further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized.” Wait and see, in other words. Could be a while. Put your venison sandwich back in the fridge, don’t want it to go bad.