We found that the ion channel protein complex assembled by Ankyrin-G at mammalian axon initial segments and nodes of Ranvier is also present at the axon initial segments of lamprey eels (figure, right). Lampreys, the most ancient of living vertebrates, evolved nearly 500 million years ago. This is about 50 million years before vertebrates with myelinated axon first appeared. Our findings suggest that ankyrin-G dependent clustering of sodium channels via anchor motifs evolved even earlier, however, in small wormlike creatures that are the closest invertebrate relatives of the vertebrates (see cartoon). We are studying these organisms, the basal chordates, to understand how this molecular and cellular innovation emerged. These organisms offer many technical experimental advantages, but the work also is of broader, even philosophical interest. Evolution is often described as a series of changes in visible body shape (Darwin's "endless forms most beautiful"). In this case it appears that an inconspicuous molecular innovation, allowing the individual neuron to signal more rapidly and reliably, may have preceded and made possible the larger brains, larger bodies, and particular forms of complex behavior characteristic of vertebrates. This is a grand and idealistic notion, and an old one--as per the German playwright, poet, philosopher and historian Friedrich Schiller (1759-1805): "it is the mind, itself, which builds the body". (Thanks to Tom Schwarz and Jeffrey Hamburger for sharing the Schiller quote-carved in stone at Harvard).