Much like the "microbe hypothesis" put forth over 150 years ago, the "prion hypothesis" can be definitely proven only if a prion disease is engendered in a natural host from an infectious prion produced in vitro. In this issue of Cell, come very close to accomplishing this goal by producing a prion disease in a natural host from a prion entirely generated in vitro using a PCR-like amplification system.
Division of Neuropathology, Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH 44106, USA.