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Starting work on spherical viruses


An argument leads to a grant from the National Institutes of Health
Aaron Klug Scientist
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So I then began working on Tobacco Mosaic Virus. And as you know, we published the map, at 10 angstroms by 1971, by which time Ken Holmes had left to go to Germany. But...

[Q] But, there was a row, wasn't there, over the... over TMV?

Oh, yes, yes, what happened was that we used to get our supplies... we used to get our supplies of Tobacco Mosaic Virus... from [Norman W] Pirie who was virologist at Rothamstead. And Rosalind [Franklin] once published a paper to say that Tobacco Mosaic Virus was a long rod of 6,000 angstroms long. And which was... had been seen by Robley Williams and it contained... a number of nucleo... a number of bases it contained in the RNA. But the... he... so Pirie took exception to this and he stopped sending us material. He said, as far as he's concerned, Tobacco Mosaic Virus is a collection of rods of different sizes and all the preparation is infectious. You don't have to have the infectious particle; it isn't necessary, the 6,000 angstroms, the long, unbroken rod. And he was a... Pirie was an interesting man, very clever man, one of these clever people who are... so clever they drag themselves into false conclusions. I remember, at the time in 1950s, going back a bit to when I was at Cavendish, he wrote an article in Penguin Science News, which most of the sort of budding scientists read at the time. This was NW Pirie, who'd been lecturing at Cambridge, very influential, very clever man, very influential and sort of charismatic. And very keen with that sort of... he went to Rothamstead; he was also sort of a... very left wing like Bernal. But the... he... he wrote an article and he said... just imagine the protein, you see, nobody had worked out the structure of a protein. And he... first of all he questioned whether a protein had the structure, a definite structure. He pointed out: if you had a three dimensional structure of a protein and you replace a valine by an isoleucine it wouldn't make any difference. Indeed, that's... that's true generally, these are just silent mutations or silent changes, polymorphisms as they're called. But, of course, he didn't know about sickle cell haemoglobin; if you change a valine into a glutamine the whole thing is... it's disease... it's a disease gene which is sickle cell anaemia.

[Q] But he wasn't persuaded by Bernal's photographs going out to, two angstroms or whatever.

No, no, that wasn't... no, he wasn't. He was, you know, he was... as I've said, he was a... one of these guys who was a bit too... too clever is not the right word, too firm in his opinion... he never thought he could be wrong, which is one of the things you have to learn.

[Q] With serious... consequences on the financial situation from that.

Well... well...

[Q] He was on the ARC.


[Q] Yeah.

So... but he... but... so in the end the ARC grant began to... looks as though it was going to end.

[Q] Yes.

And Rosalind went to see Sir William Slater who was the Head of the Agricultural Research Council and he patronised her. He said, 'Oh, well, we have an X-ray set in Sheffield; you have to move to Sheffield, we'll fix you up there'. And no understanding at all, and I think, partly because she was a woman he... in those days there were people who didn't take women scientists very seriously, it was very different. Dorothy Hodgkin could charm her way through anybody but Rosalind wasn't like that, she was quite fierce as you know.

[Q] Yes.

But, she phoned me up almost in tears to say to me, no renewal of the grant; so we didn't know what to do. I had my own... I had my own fellowship but this was going to run out and... so to the rescue came Robley Williams from Berkeley. He was a distinguished electron microscopist, he came from Berkeley, the famous virus lab. And he was visiting Cambridge, working in Kenneth Smith's lab for a year, and he suggested we apply for a grant to the American, the US National Institutes of Health.

[Q] Yes.

And I... none of us knew if we could get a grant from the American body, and he said, 'Well, you can if you're working on something which nobody in the States is doing.' So we applied to the NIH, and by this time, I can't remember whether we already started to work on spherical viruses, I think we had; but the main thing was NIH.

[Q] Yes.

And Robley Williams... so we applied and Rosalind was the principal investigator and I was the co-investigator. And it was very business-like, Robley Williams came again on a visit and he was made a... I didn't know what a site visit was... he made a site visit. He said to... he said to us, 'If you get a centrifuge' – because we didn't have a centrifuge – 'to prepare the virus, where will you put it.' And he went out, and who will you do this and how will you do that? It was all very business-like; of course, we answered him and we got the grant. Now, the grant was for £10,000 a year for three years, that's £30,000. Now, nobody had ever got any grant of this size at Birkbeck before, not even Bernal or anything. So the... Andrew Booth, who was on the Council told us later that he misunderstood, he thought it was £10,000 for the whole three years and if he had heard... if he had realised it was £10,000 a year he would have voted against it because he thought this would give an undue advantage to certain people. And we, in the College, his idea was, you know, as that sort of British defeatist, that you have to share your misery, and it was quite a... And then, of course, we had to... our salaries had to come from the grant as well, so Sir John Lockwood, who was the Master of Birkbeck, beat us down, Rosalind and myself to the lowest possible level. I remember what he said; 'You have to... you have to work for the love of the subject... the love of the subject.' We were living in a... at the top of an attic... flat in... in Chalk Farm and so on, we had one small child by this time.

[Q] Yes.

So... anyway, but it did... that grant did save us and enabled you... enabled to transfer the... and we were able to... we bought another X-ray set, I can't remember. So that was a great change.

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: John Finch Ken Holmes

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.

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.

Tags: National Institutes of Health, Agricultural Research Council, Rosalind Franklin, Norman W Pirie, Robley Williams, Sir William Slater

Duration: 7 minutes, 14 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008