An immortal pathogen
Funerary cannibalism, pathogens both immortal and fully lethal, rapid and relentless psychosis, insomnia, starvation. Prions may occupy the same space in pop culture as Casey Anthony and plane crash dissections. Real-life horror stories permit us to feel a sort of safe terror. For many of us, a typical Saturday night involves copious amounts of fast food accompanied by spooky video essays about the loss of human life. This kind of lapse in empathy requires us to believe that whatever is experienced by the human subject of the video is extremely unlikely to impact us or our loved ones. True crime has been criticized for inciting this alienation; in the effort to dramatise tragic events, the genre ultimately trivialises them. This could also be true for prions.
On that account, it is good for our hearts that we get serious and learn about prions. I know, very boring. But, in the words of David Lynch, “Fix your hearts or die”.
In 1982, Stanley Prusiner identified the “proteinaceous infectious particle,” which he coined “prions.” This was a paradigm shift. Before Prusiner’s discovery, all pathogens were believed to carry some form of nucleic acid, RNA or DNA. Prions do not. Pathogens need to replicate to survive, and nucleic acids are really the only way for a virus or another pathogenic organism to stably replicate itself. This does not apply to prions. Before 1982, diseases like Kuru and Creutzfeldt–Jakob disease (CJD) were known as “slow viruses” due to their potential for long incubation periods before rapid disease onset. Prusiner demonstrated that these pathogens were effectively immortal; he subjected them to treatments that destroy nucleic acids and showed that they retained their infectiousness. Prusiner linked the prion protein (PrP) to these diseases.
PrP, the protein that causes CJD, Kuru, and fatal familial insomnia (FFI), is expressed in all our brains. You might be terrified or, at the very least, confused if you don’t know anything about protein folding. In short, when your proteins are made, they fold into complex structures which directly inform their function. PrP can generally exist in two main forms. The common, healthy form is cellular prion protein (PrPC). The scary one is scrapie prion protein (PrPSC), named after a prion disease affecting sheep. In general, prion disease occurs when PrPC misfolds, adopting a PrPSC conformation. PrPSC is thought to act as a template for the healthy PrPC to misfold. In other words, PrPSC is infectious. You can develop prion disease in a few ways: inheritance through mutations in the PRNP gene; infection by exposure to PrPSC in a lab, a factory, or on your plate; or sporadic cases, caused by the spontaneous misfolding of PrPC. To make life hard for scientists, sporadic prion disease doubles as the most common and confusing form. Much of today’s research into prion disease involves studying the structures of PrPC and PrPSC, the conditions that favor misfolding, and how exactly PrPSC causes the brain to devour itself.
Prions kill fewer than 100 Canadians each year, so what is the use in dedicating time and public resources to study them? I’ll offer two related justifications. First, PrP is not the only protein that spreads its own misfolding. Alpha synuclein, associated with Parkinson’s Disease (PD) and Dementia with Lewy Body (DLB), and amyloid beta, associated with Alzheimer’s Disease (AD), are both well-expressed proteins that have been shown to sporadically misfold and propagate in the brain in a prion-like fashion. PD, DLB, and AD are significantly more common than CJD, Kuru, and FFI. This leads into my second point. Studying the way PrP misfolds and destroys brain tissue will lead to collateral discoveries about broadly applicable topics, such as neuroinflammation and cell death, thereby improving our understanding of how the brain functions and how to protect ourselves from neurodegeneration.