Known knowns, known unknowns, and unknown unknowns: can systems medicine provide a new approach to sepsis?

"As we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns—the ones we don’t know we don’t know." Donald Rumsfeld's statement as US Secretary of State for Defense during a news briefing in 2002 attracted much publicity and comment. Despite several decades of laboratory and clinical research, Rumsfeld's assertions can be applied to the current state of knowledge about sepsis, acute illness, and anaesthesia.