Aaron Klug

Aaron Klug's career has taken many turns, spanning physics, biology, chemistry, and administration. 

Josh Roberts
Aug 1, 2004

Aaron Klug's career has taken many turns, spanning physics, biology, chemistry, and administration. The names that he drops occupy an integral place in this soft-spoken 77-year-old's life story: from Rosalind Franklin, with whom he began working on the structure of tobacco mosaic virus (TMV), to Buckminster Fuller, whose geodesic domes inspired Klug's ideas on spherical viruses.

Born into a Jewish family, Klug moved at 2 years of age from Lithuania to South Africa, where he was schooled in the English tradition. At 15 he attended university in Johannesburg and toyed with the idea of becoming a scholar, a linguist, or an Egyptologist, perhaps, but ultimately he pursued a science degree instead. He went on to study, and later revolutionize, crystallography.

You've made some major contributions to the sciences. Do you have a favorite paper?

Courtesy of MRC Laboratory of Molecular Biology

My favorite, although not the most important, is...

What would you consider your most important work?

Starting a totally new subject: three-dimensional image reconstruction.

The images you see in an electron micrograph are projections of everything in the line of view, superpositions of the 3-D structure. John Finch and I built models and showed that if we tilted the model through different angles and photographed it, we could explain the images. Now having done this I began to wonder whether we could go backwards. I developed a mathematical method using Fourier analysis to reconstruct the three-dimensional structure from a series of two-dimensional images. I also realized that this was the way to do medical radiography.

There's now a whole school of structural biologists who use EM for solving structures. It now competes with and supplements X-ray crystallography, but you don't have to have crystals.

Godfrey Hounsfield read my paper, and took out a patent for a machine that would do this in X-radiography. He developed the first brain scanner, which hit the world in the early 1970s. He got the Nobel Prize with Alan Cormack in 1979.

Some people think I should have gotten the Nobel Prize with them, because the principle they use is my principle for 3-D electron microscopy. I showed how you could do it, in a different context. I worked out all the necessary conditions.

Are you bitter?

No ... I was somewhat surprised. I thought I might be. But it all worked out all right in the end.

In 1982 I got the undivided Nobel Prize in chemistry for the "development of crystallographic electron microscopy and the structural elucidation of biologically important nucleic acid-protein complexes." If you interpret that, that's viruses and chromatin.

Probably chromatin was the most important biological thing I did. The nucleosome was discovered in my lab by Roger Kornberg: I put him on to doing it, but I didn't put my name onto the paper because he thought up and did some of the key experiments. He put the things together; I had learned from [Francis] Crick, who had been generous to me in such matters, and that was really the pattern in our lab.

What about your work on zinc fingers?

What I had discovered was not simply a new protein fold recognizing RNA and DNA, but also a new principle of recognition based upon the combinatorial principle. While the zinc fingers are structurally independent, they could be linked together in tandem to produce recognition of a long tract of DNA. They can switch genes on or off with a very high degree of specificity, and also control all splicing isoforms at once.

Do you expect another Nobel Prize for that work?

It's still too early to know how the medical applications will work out.

You were director of the MRC Laboratory of Molecular Biology for 10 years, and president of Royal Society for five. What motivated you?

Having had a pretty successful science career, I felt I ought to give something back. Administration wasn't really the point to it; the key was really dealing with the issues: global warming, GM crops, BSE disease. It was rather hard work, and it interrupted my scientific work. And also when I was head of the lab, I had quite a lot of directorial duties to do. But the key was to recruit and encourage talented people.

What do you do for fun?

I collect Greek and Roman coins that illustrate historical episodes. I can't afford coins of Caesar or Pompey, but I know the names of their generals who struck coins, so I collect those.

Josh Roberts jroberts@the-scientist.com