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Making mutant spectra with acid


The MRC lab at Cambridge: Computers and determining structures
Sydney Brenner Scientist
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One of the things that John did which was absolutely very far-sighted was he realised computers were going to be very important in this field. And very soon after the war he got involved with the developments that were going on here; in fact the first Fouriers were calculated on a hand-built computer in... in the Mathematical Laboratory here called Edsac II. This was a valve machine and… and in fact was something I remember I… I went there once, and there were a lot of comic books there, and I thought well, you know, these people. But it turned out these comic books were used to fan the valves to try and cool the machine. So it was… the machines were very hard to program, and in fact the whole of Autocode was invented for this, so that… the computing was a very important part – that was recognised. Plus of course all the other instrumentation. Now, of course Francis came as a physicist to do crystallography. Max and John... John had the first breakthrough on myoglobin. Well, Max had the fundamental breakthrough in which he showed the isomorphous replacement method could let you do phase. What you do is you put a heavy metal in one position in the protein and it adds its scattering to the… to all the others. So if the original scattering is positive, then they get stronger. If they were negative they get weaker – this is a very crude summary but it's roughly how you do it – and then you can compute the phase and then you can compute the structure. Now, it's... it's that structure I think, this sort of... the... the whole of doing that, when John got the first 6Å structure of myoglobin and it looked like just a roll of sausages, it was very thin, then Max got this, and of course over the years that has improved. And I think it was a feat in the sense that: one, you could determine the structure; and two, that you could begin to look at this to see whether you could understand how it functioned. And of course these days we also want to look at it to see where we can stick other molecules in and regulate it. I think there is quite a distance between the genetic thing. But what I think is quite important is to have that concept of structure, and I should add, macromolecular assembly, because Hugh Huxley had been a member of the unit, he left and went to University College, he was working on the structure…

[Q] King's.

No, University College.

[Q] I beg your pardon.

And he was working on the structure of muscle. And of course later on we brought people doing virus work who came to join us in the '60s.

South African Sydney Brenner (1927-2019) was awarded the Nobel Prize in Physiology or Medicine in 2002. His joint discovery of messenger RNA, and, in more recent years, his development of gene cloning, sequencing and manipulation techniques along with his work for the Human Genome Project have led to his standing as a pioneer in the field of genetics and molecular biology.

Listeners: Lewis Wolpert

Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of Anatomy and Developmental Biology of University College, London. His research interests are in the mechanisms involved in the development of the embryo. He was originally trained as a civil engineer in South Africa but changed to research in cell biology at King's College, London in 1955. He was made a Fellow of the Royal Society in 1980 and awarded the CBE in 1990. He was made a Fellow of the Royal Society of Literature in 1999. He has presented science on both radio and TV and for five years was Chairman of the Committee for the Public Understanding of Science.



Listen to Lewis Wolpert at Web of Stories



Tags: Cambridge Mathematical Library, EDSAC 2, University College, 1960s, John Kendrew, Francis Crick, Max Perutz, Hugh Huxley

Duration: 3 minutes, 23 seconds

Date story recorded: April-May 1994

Date story went live: 24 January 2008