Protein-only prions

When Stanley Prusiner proposed the protein-only hypothesis of prion infectivity, he envisioned a simple experiment. Make the protein in vitro, and infect the mouse. Now, Giuseppe Legname, Prusiner (University of California, San Francisco, CA), and colleagues have done just that, albeit with a lack of potency that has left some people in doubt.

The problem is that the most potent material—brain extract—is a mess. A misfolded version of the endogenous PrP protein emerged decades ago as the putative infectious agent. But in infected brains it is clumped in an insoluble amyloid form that is difficult to purify and impossible to crystallize. Thus, the exact nature of the most infectious form is a mystery. “The only measurable thing we have right now is the amount of β-sheet,” says Legname. “We do not know...