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Electron microscopy: defocussing to see transparent objects


Image reconstruction in electron microscopy
Aaron Klug Scientist
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We spent several years on all this, on spherical viruses. Mostly Don [Caspar] and myself and then we were joined by Tony Crowther... who was a... trained in.... he had a... he had a degree in mathematics from Cambridge but he'd built a scanner, working with David Blow, he joined us and he put everything on a sound basis. Of course, the way that we used... we used Fourier transform theory to build up a three-dimensional image. We sometimes had more projections than we needed, so he introduced what was called the squares analysis to try to put this altogether on a regular basis. So we created a new subject which was image reconstruction in electron microscopy. Now, I've gone on quite far ahead because it all was intertwined and it's hard, now, to go back again and see how the progress came about. But you can sum it up; the reason we were able to do this was we were working on concrete problems and that, I think, is pretty important. It's not by... I could have sat down in one afternoon and written out a theory if I'd actually thought that it was going to do it. It was not very... if you know some Fourier transform theory and some X-ray crystallography, you can write down this theory in one afternoon, but it didn't work like that. It took many years to realise what it was that we were doing and how we were doing it. So I do think that the moral there in science, that these more general principles arise out of particular cases. And I think that there are other instances of this as well, we've studied one concrete example or several concrete examples to arrive at the generalisation, that's the... that's the way that I think our minds work.

Born in Lithuania, Aaron Klug (1926-2018) was a British chemist and biophysicist. He was awarded the Nobel Prize in Chemistry in 1982 for developments in electron microscopy and his work on complexes of nucleic acids and proteins. He studied crystallography at the University of Cape Town before moving to England, completing his doctorate in 1953 at Trinity College, Cambridge. In 1981, he was awarded the Louisa Gross Horwitz Prize from Columbia University. His long and influential career led to a knighthood in 1988. He was also elected President of the Royal Society, and served there from 1995-2000.

Listeners: Ken Holmes John Finch

Kenneth Holmes was born in London in 1934 and attended schools in Chiswick. He obtained his BA at St Johns College, Cambridge. He obtained his PhD at Birkbeck College, London working on the structure of tobacco mosaic virus with Rosalind Franklin and Aaron Klug. After a post-doc at Childrens' Hospital, Boston, where he started to work on muscle structure, he joined to the newly opened Laboratory of Molecular Biology in Cambridge where he stayed for six years. He worked with Aaron Klug on virus structure and with Hugh Huxley on muscle. He then moved to Heidelberg to open the Department of Biophysics at the Max Planck Institute for Medical Research where he remained as director until his retirement. During this time he completed the structure of tobacco mosaic virus and solved the structures of a number of protein molecules including the structure of the muscle protein actin and the actin filament. Recently he has worked on the molecular mechanism of muscle contraction. He also initiated the use of synchrotron radiation as a source for X-ray diffraction and founded the EMBL outstation at DESY Hamburg. He was elected to the Royal Society in 1981 and is a member of a number of scientific academies.

John Finch is a retired member of staff of the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. He began research as a PhD student of Rosalind Franklin's at Birkbeck College, London in 1955 studying the structure of small viruses by x-ray diffraction. He came to Cambridge as part of Aaron Klug's team in 1962 and has continued with the structural study of viruses and other nucleoproteins such as chromatin, using both x-rays and electron microscopy.

Tags: Don Caspar, Anthony Crowther, David Blow

Duration: 1 minute, 59 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008