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The decision to join the Cavendish Laboratory


The gene protein problem
Sydney Brenner Scientist
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I spent about eight weeks in… in the Virus Lab, and then of course the time came for me to go back. By this time I knew exactly what I wanted to do. I had formulated what had be… what we had come… was the gene protein problem. That is, we would investigate the correlation between genes and proteins by getting a gene on which we could do fine structure analysis, and then its corresponding protein on which we could do chemical sequencing. And the first question was to prove co-linearity. Namely that the mutations occurred in the gene in the same order with which they were present in the proteins. Now, of course that was inspired by work that had been done by Vernon Ingram, who actually showed that sickle cell haemoglobin, which Pauling had showed involved a chemical change, Vernon showed was a singular change, the conversion of one glutamic to a lysine, within one place in the haemoglobin. And he'd invented a fingerprinting method to show this. And so we were going to fuse these two technologies in order to start to investigate the relation between genes and proteins. And of course at that stage everything was enormously difficult to do. And you had to get large amounts of protein to do this. Haemoglobin... you can get grams of haemoglobin. And so we had… and what had happened then…

[Q] When you say we, where were you now Sydney? I'm slightly confused.

I'm still travelling.

[Q] You're still travelling, so…

I'm still travelling back with pieces of paper and I'm just filling in the background. And on the... and so one of the thoughts was the program that had been developed was that we would have to do, we would either have to find the protein of the rII gene, which actually never succeeded, or we would have to find another gene which… which did a phage and which… which specified something in the virus and on which we could do fine structure. And one of these genes was the host range, which George Streisinger was working on, and another of these genes was something in which… had been worked on and for which there was evidence, and it was cofactor requirement of bacteriophages. There were some bacteriophages that were not absorbed unless tryptophan was present. And so there were natural variations of this and I thought I could get mutants of these. That is something that Delbrück himself worked on, from the kinetic point of view.

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: The Virus Lab, Berkeley, Vernon Ingram, Linus Pauling, George Streisinger, Max Delbrück

Duration: 3 minutes, 19 seconds

Date story recorded: April-May 1994

Date story went live: 24 January 2008