Woods Hole, had introduced him to the squid axon preparation. Most of Frank's initial work on the giant axon was done with the modestly sized squid, Loligo pealii, which is abundant in the Atlantic waters off Cape Cod. But in the late 1950s, while visiting the Chilean Marine Biology Station at Viña del Mar, Frank encountered the elephant of the squids, Dosidicus gigas, whose axons reach diameters of up to 4 mm, in the Pacific waters of the Humboldt Current. This preparation allowed Frank and his team—stateside as well as Chilean investigators—to study the chemical constituents of the axoplasm, as well as axonal flow and transport, in individual nerve fibers.

Frank's preeminent motivation for studying nerve cells was to fathom the function of the human brain and, ultimately, nature's deepest mystery, the mind. Towards that goal, invertebrate nervous systems such as that of the squid were good objects on which to start. Yet, they are only a start, because what Frank wanted to know was not merely how the human brain senses the world and produces appropriate motor responses to it, which is what the squid brain does too, but he reached out for understanding mental functions such as memories, thoughts, and emotions, of which squid brains are unlikely to be capable. Drawing on his earlier experience with the Biophysics Study Program and fully aware of recent advances in disciplines cognate to neurobiology, Frank decided that the time was ripe for creating a basis for a novel multidisciplinary approach to the questions of how nervous systems mediate behavior and how mind is instantiated in the brain. To get started on this novel approach, Frank organized two seminar series at MIT in 1960 and 1961, which brought together people who were interested in bridging the gap between physical, chemical, and structural studies of the brain on one hand and behavioral, psychological, and psychiatric studies on the other.