From chloroplasts to chaperones: how one thing led to another

Two lessons I have learned during my research career are the importance of following up unexpected observations and realizing that the most obvious interpretation of such observations can be rational but wrong. When you carry out an experiment there is usually an expectation that the result will fall within a range of predictable outcomes, and it is natural to feel pleased when this turns out to be the case. In my view this response is a mistake. What you should be hoping for is a puzzling result that was not anticipated since with persistence and luck further experiments may uncover something new. In this article I give a personal account of how studies of the synthesis of proteins by isolated intact chloroplasts from pea leaves eventually led to the discovery of the chaperonins and the formulation of the general concept of the molecular chaperone function that is now seen to be a fundamental aspect of how all cells work.