The concept of a barrier between blood vessels and the brain and spinal cord had existed since the late 1800s, when immunologist Paul Ehrlich found that intravenously administered dyes failed to stain certain regions of the brain, whereas other body tissues were stained. Ehrlich thought the dyes did not have a staining affinity for the brain, but his student, Edwin Goldman, showed that the dyes could stain brain tissues but could not cross a barrier into the brain.
But until 1967, it was not clear whether the structural basis for the barrier was at the level of the endothelium, the astrocytes or glial cells in the brain, or the basement membrane. It took the high resolution of electron microscopy, the development of sensitive tracer methods, and a fortuitous lunch date between Thomas Reese and Morris Karnovsky to show that the endothelial cells in the brain...