The Unexpected Vista by Fred Sigworth

In science one comes from time to time upon a vista, a place where with the sight of imagination or sometimes with direct observation a new landscape opens up before the eyes. Being a scientist brings with it the privilege of being the one to see some of these vistas for the first time. Being in the academic community of the university also means that one has comrades who can understand and share the excitement-since science is a community effort that involves both discovery and the sharing of knowledge. As a psalm summarizes it, "One generation shall declare Thy works to another."

In the latter 1970s, when I was a graduate student at Yale, the concept of ion channels as discrete protein molecules was just becoming clear. It was known for example what the total sodium conductance of a cell membrane was, but we did not know how many sodium channels operated to control this permeability. My advisor gave me considerable freedom, basically turning me loose in his laboratory to try out my new approach to estimate the single-channel conductance. The approach worked, resulting in an estimate for the number of picosiemens of conductance per channel, and resulting in a PhD thesis. The experiments also gave evidence that the way the channels regulate their conductance is by the rapid, random switching between "on" and "off" states. The evidence was indirect-it involved the statistics of fluctuations in the sodium current-but it was convincing to me, and to those people who understood the theory involved.

One evening two years later I was riding home on my bicycle, full of wonder at a new experiment just completed, in which I had seen on an oscilloscope screen the individual square pulses of current from sodium channels for the first time. It is maybe not for everyone to be so excited that one can "see" the workings of one ion channel on an oscilloscope screen, but for me and some of my colleagues, it was an event that we had looked forward to for some time. The "vista" opened up by this single-channel recording was better than what I had imagined.

Perhaps you have learned about something that has you intrigued. Maybe you feel the motivation of wanting to understand, to see a biological process more clearly. You would like to read about what is known, and spend time contriving experimental ways to see it better. This is the kind of motivation I have felt. In my case, I first heard about ion channels as an undergraduate student in applied physics, and was intrigued by the idea that protein molecules could act as devices like transistors, switching electric currents in response to voltage changes. The mechanism by which channel proteins do this has turned out to be a remarkable one, and one that I would still like to see more clearly.