To me it was most enlightening to examine the website of Professor Desai's department ( the Department of Bioengineering and Therapeutic Sciences ). The department focusses on four areas-- (1) Computational biology and systems pharmacology, (2) Drug development and regulatory sciences, (3) Pharmacogenomics and Genomics, and (4) Therapeutic Bioengineering. Reading about the current research projects in that last area, I was struck by two things: (1) they conform much more to what I consider traditional bioengineering than they do to Dan Koshland's type of bioengineering, and (2) they are spectacularly beautiful, bringing, for example, cutting-edge submicron-technology and chemistry to bear on biological systems. The therapeutic structures they are designing, fabricating and employing are extraoridinarily tiny. I was taken back to my student days, the mid-1950s. Stanford's EE faculty included Karl Spangenberg-- world authority on the physics and design of vacuum tubes. Professor Spangenberg retired just as physical electronics was moving into the era of solid-state electronics, integrated circuits and the dawn of submicron technology. In a few decades, functional circuits incorporating the equivalents of many millions of Professor Spangenberg's vacuum tubes would be fabricated on small silicon chips. Nearly fifty years later, I too had retired from research just as bioengineering was moving into its era of nanotechnology.

Then it occurred to me that my collaborators and I had been immersed in a sub-micron world for a very long time. In fact, submicron silicon technology actually had been employed by neurobiologists since the late 1940s, when Gilbert Ning Ling and Ralph W. Gerard introduced the glass micropipette electrode. When I arrived at Berkeley, I inherited a device (electrode puller) for fabricating such electrodes. At first we used it largely for work on invertebrate neurons and sensory cells. About a decade later, my colleagues and I began using it for our work in the vertebrate VIIIth nerve. We adjusted the puller's parameters to yield hollow glass electrodes with tip diameters of approximately 80 nanometers, and with these we observed and recorded the neural signals being sent from the vertebrate inner ear to the auditory or vestibular brainstem. Actually, when we first began using these glass electrodes, we wanted to do more than merely observe and record signals-- we wanted to create detailed functional maps of inner-ear sensory surfaces. For that purpose, we needed to position the electrode tips inside VIIIth-nerve afferent axons with diameters as small as two microns. That would allow us to observe each axon's signals, then inject dye molecules into it through the hollow tip of the electrode. For observation and recording alone, we would merely have needed to penetrate the larger-diameter myelin sheath surrounding the axon. Injected into the sheath, the dye would spread only through one segment, from node to node. Injected into the interior of the axon, the dye could spread from end to end-- to the axon's target hair cells in the ear and to its target neurons in the brainstem. Thinking about these things reminded me of lines attributed to Bernard of Chartres at the dawn of the Renaissance and echoed later by Isaac Newton in a letter to Hooke. In the Lewis Lab, we definitely were making small advances with tools and concepts given us by giants, including Ling and Gerard. Click here for more on our adventures in the submicron world.