Robert S. Eisenberg
Life Glimpsed through Ion Channels
A Super Short Scientific Biography
November 13, 2015
I have been interested in how physical things work as long as I can remember, and in how living things work nearly as long, from the day my father (a physician and then psychiatrist) showed me that was the best way to mold my interests to his approval.
At Harvard John Edsall was my tutor, and he did in fact tutor me, biweekly at first and then (nearly) weekly, nominally in biology, but really in the wisdom of science. (John Edsall was born the son of a Dean of Harvard Medical School, and was a fulcrum for the pivotal change from macroscopic to molecular biology at Harvard and elsewhere, training Bruce Alberts, David Eisenberg, and Jared Diamond among many other distinguished scientists.) My coursework was in physics, chemistry, applied mathematics, and electrical engineering, but, if my memory serves me correctly, not in biology at all. (I actually love evolutionary and descriptive biology as I love collecting classical CD’s but those loves are hobbies more than anything else.) My undergraduate thesis solved the cable equation of physiology (the transmission line equations of engineering) with a Green’s function, reproducing in an elegant but useless way what I had learned from Morse & Feshbach about heat equations.
My graduate work was experimental at University College London, where my department chairman Bernard Katz was to win the Nobel Prize a few years later. Fortunately, Andrew Huxley (Chair of Physiology at UCL, winner of the Nobel Prize with Alan Hodgkin in 1964 a year or two before Bernard Katz, if I remember correctly) liked solving the cable equations the way I had, happy to spend many hours teaching me, on the side, as if he didn’t have enough else to do. My experimental work measured the spread of current in crab muscle fibers over a range of frequencies, using impedance spectroscopy, as it is now rather pretentiously named.
I will not describe the many decades of experimental work I did analyzing the flow of current in muscle fibers and then the lens of the eye, except to say we learned a lot. It is easily found on-line. I became a Department Chairman at Rush Medical College in Chicago in 1976: the temptation of an Endowed Chair was enough to make a 34 year old move from the perpetual spring of Brentwood (LA) to the recurrent vagaries of midwestern weather. In the 1980’s, I started thinking about the theoretical problem of describing ion movement through the water filled tunnels of charge we call ionic channels. That led me to study ions in bulk and in channels and to realize the strenth of the electric field. Conservation of charge and conservation of current are universal, inside protons and between stars. Sadly, classical chemical thinking more or less ignores the electric field. Classical chemical kinetics, and the Markov models of physiological fame, in fact violate conservation of current and so cannot be used (over a range of conditions with one set of parameters) to describe most living processes, or most of our technology, because they do not function (or even exist) without current flow. The chemistry of a battery depends on the circuit it feeds with current even though that is meters away. Biological and technological systems depend on current flow far from the atomic systems that evolution and engineers build to control that flow. Our models, simulations and theories must therefore include the electric field far away and its boundary conditions. The thermodynamic limit is too limiting in life or technology. It must be extended with a hierarchy of multi-field theories, in which ‘everything’ interacts with everything else, and so must be analyzed with energy variational methods.
The ionic channel is where we still are; but gazing through this narrow hole has proven to be rather like looking through a keyhole in a door. The closer you get to it, the further you can see, even glimpsing the horizon (of knowledge) occasionally, even seeing a star or two, when all else seems dark.