Image: ARNOLD ADLER/The Rockefeller University
I met with MacKinnon in New York City at his Rockefeller University office overlooking the East River to ask about his work and his aspirations. The interview that follows falls into five sections. In the first part MacKinnon gives a mini lecture on the nature of electrical signals in living organisms, ion channels and the fascinating intricacies of their structure. He also explains the riddle of why potassium channels act like money machines that take nickels but not dimes. In the second part he touches on the hard labor he and his lab endured to identify the structure, as well as its potential applications for medicine. In the third part he voices his thoughts on the Lasker and the Nobel Prize and on his short- and long-term research plans. In the fourth part he discusses his past and divulges why he switched to a career in science after eight years in medicine. Finally, MacKinnon the trout fisherman talks about how he likes New York and why he left Harvard and NIH funding for risky research projects.
SA: You have devoted your entire scientific career to studying ion channels. Why don't you start by telling me a little bit about why they are so interesting?
RM: There are many facets in the answer to that question, but one of the first things that fascinated people in general, even before they knew ion channels existed, were questions like "What is the basis for electrical signals in living systems? How is life electric? What is the electrical nature of living cells?"
A really obvious observation that people made early on is the very simple aspect of moving. I hold my hand out and I wiggle my finger. Obviously, a thought originated in my head--that I want to wiggle my finger--and then I wiggle my finger, and somehow there must be information getting all the way down to the muscles in my finger to make them wiggle, and that happens very fast.
It was understood early on, more than 50 years ago, that there are electrical signals that propagate down extensions of nerve cells called axons. And so a half century ago, even before then, there was an effort to understand what is the nature of these electrical signals, how do they happen. [Alan] Hodgkin and [Andrew] Huxley, two scientists from England, came up with a theory for how it happens. Their theory was that the nerve extension, the axon, is like a cable, an electrical cable, where the cell membrane is the insulator around the cable, and the salt solution inside the axon is the conductor, as is the salt solution on the outside of the axon. And when they put their own and other people's information together, their theory predicted, among other things, that the cell membrane had to undergo changes in its permeability.
That is, the cell membrane first had to be such that ions, which are the charged atoms, don't cross the membrane very well, and then suddenly the membrane, in a little region, becomes very permeable. So first sodium goes across the membrane very well, and then shortly thereafter the membrane loses its permeability for sodium and then becomes permeable to potassium. This was a very central part of their theory. Since then people have tried to figure out what is it about the membrane that allows it to undergo its changes in ion flow, in its permeability. And people figured out that there had to be pores in the membrane, and those were called ion channels.