Unfolding the Prion Mystery

PRIONS are creepy. Although not alive by any accepted definition, these unusual particles ––believed to cause diseases such as mad cow and chronic wasting disease––still manage to propagate by deforming normal proteins, triggering a chain reaction with typically fatal results. They are lethal in vanishingly small doses, and as opposed to viruses or bacteria, which succumb to environmental conditions or antibiotics, prions are resistant to extreme temperatures, radiation exposures and many chemical treatments that kill any life. For all of these reasons, the fight against prion-related diseases largely relies on understanding and stopping the movement of the pathogens. It‘s a battle of containment.

Since the first cases of CWD surfaced among deer in southwestern Wisconsin in 2002, the state Department of Natural Resources has waged that war using hunters and sharpshooters to kill deer in a targeted exclusion zone. At the same time, UW-Madison launched a significant research effort to study and explain the strange protein that seems to be at the root of the outbreak. The good news is that recent research has filled in some blanks about the movement and behavior of prions. The bad news is that the results suggest that prion control will be extremely difficult.

Just this summer, in one of the most notable studies to date, Joel Pedersen, a CALS professor of soil science, and Judd Aiken, a virologist in the UW School of Veterinary Medicine who studies several types of prions, reported a drastic increase in prion transmission when prions attach to clay particles in soil. Pedersen says the finding could explain how the disease is transmitted among deer in southwest Wisconsin: Saliva, urine or feces dropped by deer can make soil infectious.

“Our studies on prion disease transmission underscore the need for wildlife managers to consider soil as a potentially important environmental reservoir of infectivity,” Pedersen says.

A Warning––and a Disaster

More than 200 years ago, Scottish shepherds found that some of their animals seemed to itch uncontrollably, and noting that the affected sheep compulsively scraped up against rocks and trees, they nicknamed the condition “scrapie.” It would be the first of a host of related degenerative diseases observed in mink, deer, elk, cats, bovines and humans that followed a similar destructive pattern. In each case, some infectious agent got into an animal’s nervous system and set to work chewing up its brain, causing an invariably fatal disease.

Not until the 1960s did scientists theorize that the infectious agent might be a prion, an otherwise normal protein that somehow folds itself into the wrong shape and somehow––there’s that word again––distorts other prion proteins in a cell. Able to propagate despite having no DNA or RNA, prions seemed to defy the laws of biology, and some considered them too good––or too bad‚––to be true until California biologist Stanley Prusiner isolated them in the lab in 1982. That finding was “intellectually shaking,” recalls Elizabeth Craig, a CALS professor of biochemistry who studies proteins. “Self-propagation was associated with DNA and RNA. It was shocking to find it without either one.”

Prions grew considerably more mainstream in the 1990s, when an outbreak of mad cow disease in the United Kingdom forced that nation to cull millions of cattle to control the infection. Since the start of the epidemic, about 150 Britons have died of a human prion disease called variant Creutzfeld-Jakob disease, apparently as a result of eating infected beef.

UW-Madison scientists have played a critical role in the exploration of the prion diseases, and indeed, had the warnings of a Wisconsin virologist been heeded, the United Kingdom might have been spared the mad cow disaster, or at least controlled it much sooner. Beginning in 1990, Richard Marsh MS’66 PhD’68 cautioned that dairy cows might get infected from feed that contained byproducts from prion-infected cows. (In many countries, inedible byproducts and the carcasses of diseased cattle are treated with heat or chemicals before being blended into animal feed.) Marsh, who had grown up on a mink farm, reached this conclusion after studying a 1985 outbreak of prion disease at a mink farm in Stetsonville, Wis., which killed 60 percent of the animals.