Aaron Klug on Development of Crystallographic Electron Microscopy and Elucidating Viral Structures
  Aaron Klug     Biography    
Recorded: 17 Jun 2005

I saw an opportunity. It’s always like that. I didn’t set out to discover these things, I didn’t know they existed. You’ve got to keep your eyes open. It came out of virus structure. We were building models of viruses from electron micrographs and I was interpreting the different pictures and building models and I realized I was building a picture making model building—comparing the model as though we were taking a micrograph using an ordinary light illumination to match what we could see in the microscope, so I said the information must be there and of different angles. So I realized you have to image them from different angles and then combine them and that required a certain kind of mathematics which I knew about from crystallography. In fact I used to call it Fourier (?) microscopy. But that requires a certain jump to save it—so what I used was the experience I’ve had in x-ray crystallography and Fourier transform theory to electron microscopy. It’s hard to say how it happened. It didn’t happen overnight. I could have done it in one afternoon if I had known what—but nothing happens like that. It just doesn’t work like that. You have to try all sorts of things. You have to have your mind on the problem. But it isn’t as though you sit down and say, ah, if I used Fourier transform theory I could do it all. I started doing it by some other kinds of mathematics and I realized what I was doing. So most of research, at least in my experience, has been like that. You don’t hit home in one so to speak. But if you like to take Jim’s book about the base pairing. He was trying all sorts of things. He was trying like for like or GG if you read his book, but you have to have your mind on the subject.

When I wrote it up I could write it up in a few paragraphs and it took a long time. Max Perutz didn’t believe it.

I did in the end of course, at the beginning, yes. He [Max Perutz] was trying to—because he doesn’t understand the mathematics. He was trying to understand how, what was the physical basis for it. So he worked it out himself in his own way because he couldn’t follow the mathematics. Crick, of course, saw it instantly. And also when I worked on spherical viruses which Crick and Watson had worked on, I actually generalized geometrical theory that how you build a shell of a virus, and to do that we had to generalize it. Later on I discovered that Francis seized upon it immediately. Max Perutz I discovered in an interview later, he was glad to see that Klug’s work, this was in 1966, had all___and to explain this spherical, architecture of spherical viruses. He said, unknown to me, it was rather farfetched, you know, the theory. That’s because Max didn’t believe that—required the proteins to be flexible. So this was something which was generalization of a perfect geometrical symmetry. But by changing the symmetry, weakening it and generalizing it, you could arrive at large structures, spherical viruses, which I worked on. So Francis saw it immediately but Max believed that proteins were rigid and therefore this couldn’t happen. But Max was a very good director. I didn’t know when I was working on this he didn’t believe what I was doing but he didn’t show it. He let me go on with it. It was rather important for a mentor. He wasn’t my mentor. He was my boss. So he didn’t tell me that he didn’t believe in what I was doing because I usually talk about in lab seminars. Later we proved it of course without any doubt. But in the early days when I proposed it—this was the work with Caspar on the principles of building virus shells, so I probably should ____with Caspar.

He was in America and I was here. He came—we crossed the Atlantic. I used to visit quite a lot.

Aaron Klug is chemist and biophysicist and winner of the Nobel Prize in chemistry. After completing his BSc at University of Witwatersrand in Johannesburg, he attended the University of Cape Town on scholarship where he received M.Sc. degree. In 1949 he moved to Cambridge in England, he studied molecular structure of steel and wrote a thesis on the changes that occur when molten steel solidifies, for which he earned Ph.D. in 1952.

In 1953 he obtained a fellowship to work at Birkbeck Collage in London, where he met Rosalind Franklin. They worked together to determine the structural nature of the tobacco mosaic virus. After Franklin's death in 1958 he continued his work on viruses together with Kenneth Holmes and John Finch. In 1962 he accepted a position at Laboratory of Molecular Biology in Cambridge.

His major contribution to scientific research was the development of crystallography electron microscopy for which he was awarded Nobel Prize in Chemistry in 1982. He was knighted by Queen Elizabeth II in 1988.

More Information: Wikipedia, Nobelprize.org