Professor Jean Manson is Head of the Neuropathogenesis Division of the Roslin Institute at the University of Edinburgh. A prion is an intriguing and unique killer that became infamous in the UK when it attacked in the guise of Bovine Spongiform Encephalopathy (BSE), more commonly termed “mad cow disease”. The prion, though, does not restrict its victims to cattle; it has attacked many different species including sheep, cows, goats, deer and humans. It moves between species, as occurred with BSE passing from cows to humans in the form of variant CJD. Once it infects its victim it slowly, sometimes after many years, reaches the brain and destroys nerve cells, the neurones, and leads to death because the brain can no longer function to keep the body alive. Medical detectives have spent years trying to solve the case of this elusive killer: how does it select its victim, does it have multiple identities and how do its actions finally lead to death? This talk will take a journey through those investigations, lay out the evidence and show how understanding the elusive prion may allow a much greater insight into other neurodegenerative diseases such as Alzheimer’s disease. This lecture is part of the Medical Detectives, a series of public lectures that show how keen detective work is still essential for 21st century doctors: http://www.ed.ac.uk/news/events/medical-detectives/ Recorded on 4 October 2012 in the Anatomy Lecture Theatre at the University of Edinburgh.