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Developing 3D electron microscopy


Hugh Huxley – the best electron microscopist in the world
Aaron Klug Scientist
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One of the attractions of Cambridge was that... that there was... would be electron microscopy there. And one of the attractions, apart from people like Crick and Perutz, Kendrew, was Hugh Huxley. Hugh Huxley was at that time the... I think, the best electron microscopist in the world, in fact it's still a mystery to me he hasn't got a Nobel Prize for the work on muscle; but he was the man, the best electron microscopist, technically superb. Of course, with a very good mind, a very good, brilliant mind, in fact. And so one of the attractions was that we knew what the virus shell should look like so we should really be using electron microscopy because was X-ray diffraction takes a long time, many... many years to solve the structure by X-ray crystallography. Electron microscopy should be able to see something, so Hugh Huxley gave a two-day course, I think you went to a two-day course, I mean, it was a private course. Yes.

Now, the summer before, in '61, I went to South Africa with the family for three months. And they had... I was in the Physics Department, the old department, James had... James had retired by them. And... but they had some... I did some... I actually published a paper on X-ray diffraction of gums, I interpreted the X-ray fibre diffraction pattern. But there was also a microscope there and I remember explaining to them how to do negative staining, which had been invented by Hugh Huxley and given the name by Sydney Brenner. And I began to do... I had to go into the unit every day, so I began playing around with a technician, a man called Chick Fowle. Fowle was his name, F-o-w-l-e, he was called Chick, a very good, very capable technician, and he showed me how to use an RSEA electron microscope they had in the building. And... and I remember being very struck by it that I began taking pictures, so I learnt how to manipulate the microscope and so on. And I was also struck by something which I noticed then, which later stood me in good stead. These were negatively stained Tobacco Mosaic Virus particles, which is the old war horses we always used to look at. And it was negatively stained, which meant that the heavy metal stain was down that central hole. And the central hole appeared where it should be, well, it depends what we're talking about, the film or the print. It should appear dark as no light should go through. And I noticed I was twiddling with it, focussing it and it went white. And I... I didn't know what this was and I realised I must be changing the focus of the electron microscope. And that, I believe, was the origins. Later on, some years later when Erickson came, of phase contrast in focussing to be able to image electron microscopy transparent, as they called phase objects. So that was a pretty... again, one of these chance educational events because I wouldn't have... I didn't... it wasn't done by working out a theory which people had worked out. Later on, of course, I followed the theory.

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: Hugh Huxley, Chick Fowle

Duration: 3 minutes, 20 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008