In the ghoulish world of infectious disease agents, prions might well be the zombies. Unlike bacteria and viruses, prions have no DNA, yet still manage to replicate. Nearly indestructible themselves, the tiny agents slowly ravage the brains of their victims in an infection that is always fatal.
Prions were the culprit behind the mad cow disease outbreak in the late 1990s and early 2000s. And today, they’re driving the epidemic of chronic wasting disease (CWD) spreading rapidly through deer and elk across North America.
For nearly thirty years, Don Knowles ’88 PhD has bravely investigated these strange and elusive infectious particles. When asked if he worries, he just shrugs. It doesn’t seem to faze him. In fact, he and other scientists at Washington State University find prions intriguing—a frontier science ripe for discovery.
“The ADRU works hand-in-hand with the college in infectious disease research,” he says. It’s a relationship that has helped WSU become a leading prion research center for the nation.
In many ways, prions are still a mystery to the scientific community. Unlike run-of-the-mill microbes, prion infections have extremely long incubation periods, which often require equally long research projects. Advances in the field come in frustratingly tiny increments.
According to Knowles, every animal species naturally produces its own type of healthy prion protein. Trouble comes when something causes that protein to change shape.
“If you look back in time, it appears prion disease began with the spontaneous misfolding of these normal brain proteins,” he says.
Studies show that once misfolded, the protein mysteriously forces other healthy proteins to distort. Eventually, these infectious prions clump together into tightly wrapped fibers or amyloid plaques that destroy bits of the brain, making it appear like a sponge. Hence, the disease name: spongiform encephalopathy.
Knowles says there are four naturally occurring types of this disease in animals: sheep scrapie, mink encephalopathy, bovine spongiform encephalopathy (BSE) or mad cow disease, and now chronic wasting disease.
Humans can also develop a spontaneous form of prion misfolding called Creutzfeldt-Jakob Disease (CJD). Though not considered contagious through casual contact, it’s possible CJD prions helped fuel the notorious kuru outbreak linked to ritual cannibalism in Papua New Guinea.
In the early 1900s, the Fore people adopted the practice of cooking and eating dead relatives. These mortuary feasts, as they were called, were primarily attended by women and small children who had little access to fish or meat.
By 1950, many of the participants were dying of a type of dementia called kuru. Villagers blamed it on sorcery as victims would stumble, laugh, and eventually lose all ability to function.
In time, medical investigators concluded it was a type of spongiform encephalopathy caused by prions and spread by touching, preparing, and eating the infected bodies.
“Once they stopped the mortuary feasts, it all went away,” says Knowles. “But kuru can incubate for very long periods, so cases still crop up occasionally.
“The same thing happened with mad cow—once we stopped cows from eating other cows, BSE has all but gone away,” he says. “It’s my opinion that BSE started with the spontaneous misfolding of normal cow prions. Then, sick animals were butchered and mixed into feed supplements for other cattle, widely transmitting the disease.”
Knowles says that with mad cow, mink encephalopathy, and kuru, infectious prions do not leave the body, so disease is spread only if the carcass is opened and subsequently touched or eaten.
The scenario is different with sheep scrapie and chronic wasting disease, where infectious prions do leave the body in urine, feces, and saliva. In these cases, prions contaminate the environment, easily infecting other animals who eat tainted leaves or brush.
Thankfully, sheep scrapie has never been shown to cause illness in people. And, so far, it appears the same for chronic wasting disease. But no one really knows for sure.
David Schneider, WSU-ADRU project leader for spongiform encephalopathy research, is puzzling out the details in hopes of providing answers. His team develops ultrasensitive diagnostic tests for detecting prions in animal tissues and the environment. They also study genetic resistance to prion disease in sheep and goats.
Schneider follows in the footsteps of retired veterinary microbiologist Katherine O’Rourke ’87 PhD, who pioneered the USDA-WSU prion research program with professor of veterinary clinical sciences Steven Parish ’73 DVM. In 1998, they developed an eyelid test for sheep scrapie that provided an easier way to diagnose the disease.
Similar diagnostic improvements, together with careful breeding programs and strict regulatory measures, have dramatically reduced the incidence of sheep scrapie in the United States.
Unfortunately, the principles don’t transfer well to wild deer with CWD.
Ground contamination, extensive migration patterns, and a population explosion in white-tailed deer have disseminated the disease through deer, elk, and moose in 24 states and Canada. So far, no cases have been reported in Washington, Oregon, or Idaho.
Some have proposed slowing the epidemic with controlled burns in forests and grasslands. Though not hot enough to destroy prions themselves, fire could eliminate a large percentage of the prion-laden vegetation deer like to eat. Montana wildlife advocates also suggest using wolves as an ally in the fight against CWD.
As for killing prions directly, Schneider says radiation and boiling have little effect. Incineration, strong bleach, and some forms of autoclaving can work, but not in wildland forests.
It’s enough to cause nightmares, but Schneider is encouraged by recent breakthroughs. “Advances are being made in genetic resistance and breeding programs, antiprion disinfectants, and the development of ultrasensitive testing methods,” he says.
Indeed, Schneider hopes new assays will one day allow veterinarians to screen barnyard fences and feeders for scrapie in addition to testing sheep for infection. Other scientists are developing tests to monitor prion activity in plants and soil.
And in Woodinville, the Briotech USA company just developed a disinfectant solution that kills prions, yet is mild enough to use on tissues and medical equipment.
For now, the best advice is to avoid eating or handling sick animals and to report sightings promptly to state wildlife officials.