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3D imaging: X-ray tomography and Godfrey Hounsfield's patent


The main ingredients in modern electron microscopy
Aaron Klug Scientist
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We used to call ourselves people that worked on biological assemblies. In fact, Hugh Huxley and I had a division in the laboratory when we... because he was working on problems with muscle, and we changed the name to a... sub-division of structural studies called molecular assemblies, was that its name?

[Q] Yes.

That's right, and to distinguish ourselves from X-ray crystallographers. Yes. But, in fact, it was very interesting, we really... I think, we were the first people to really do combined X-ray work, electron microscope work, and that was the beginning of the basis of structural molecular biology. And that's what the... what it became, it's sometimes called structural biology; we actually created a new field without actually saying so or knowing that we were doing it, you know, these things get given names after the event. Because, he was working on muscle and my group was working on viruses and we used similar techniques although the overall technique were the details the way you do the things in both cases were very, very different. And... so... so by this time... this is now... Erickson would be in the 1970, 71... Yes. And we... we announced all this at various meetings, the Royal Society Meeting and the meeting in Germany, which Walter Hoppy had organised on the subject, it was in 1971. And this has become the standard method; so... so the main ingredients in modern electron microscopy are three-dimension image reconstruction taking a series of tilts. Phase contrast defocussing and the other element which had made modern electron microscopy is putting the specimens into... freezing the specimens so fast that it doesn't form ice, which would break up the... that was introduced by somebody called [Jacques] Dubochet. But before that, you see, and the reason this phase contrast was important was because Nigel Unwin had shown that if you use negative stain with a heavy metal base they stalked the object. Now, he'd been trying to build a phase contract microscope in electron microscopy which was a... and he... then he actually used electric fields. I won't go into the origin of that, that came about to try to... the analogue of [Frits] Zernike phase plate. I'm afraid this is getting all very technical but, in fact, it is the technical stuff which makes for progress in this field. And so they had... so in order to reserve a specimen, he'd introduced, Unwin had introduced glucose. He simply dried down the specimens in glucose and glucose is a substitute for water. And that gave good high resolution... and Nigel luckily had been brought up as a metallurgist and he didn't know that glucose was a closed ring. He looked up an old textbook of my chemistry and it showed that the linear structure of glucose full of... it's got full of OHs, and he thought that was a pretty good substitute for water.

[Q] Yes.

And so... And so it's a very good mis-reading. So some of the first experiments and the first structure by electron microscopy to seven angstroms was by Unwin and Henderson. Originally, they started out in catalase, which was a boring molecule and they applied it to bacterial rhodopsin. This was published in 1974, so that's where they reached the peak of... of electron microscopy in the MRC unit. I think it was the... it was followed, copied worldwide.

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: Royal Society Meeting, Hugh Huxley, Harold Erikson, Walter Hoppy, Jacques Dubochet, Frits Zernike, Nigel Unwin

Duration: 4 minutes, 1 second

Date story recorded: July 2005

Date story went live: 24 January 2008