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Deciding to work on higher organisms


Virus assembly
Sydney Brenner Scientist
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You could see that with the… with the mutants that affected the assembly of a phage, and amber mutants were studied extensively by Edgar and others of bacteriophage T4… were studied extensively by them, in which they found that all the pieces of phage that we have identified, when we smashed phage up with enzymes and had classified things as cores and sheaths and heads and used electron microscopy, the negative staining… now all extracts of these bacteria infected with phages missing in one particular gene could just be looked at. And of course a most remarkable menagerie was discovered. There were mutants with free heads and free tails – they hadn't glued them together. There were mutants in which the heads hadn't formed but formed polyheads. These are long, long tubes. There were polysheaths. And using all of this one could now get on to studying the most interesting questions of... of virus assembly. And the whole idea that this is made by a kit, that you make the parts first and then the parts stick together; really I think opened up the whole of the concept of how you make elaborate cell structures, and by this hierarchical self-assembly mode. And so they... by using all of these techniques, that could be studied; there were similar things in… in lambda, studying the assembly of lambda, identifying all the genes. But the interesting thing is… is that one needed some kind of in vitro technique. That is, although the genes gave you… although the temperature… although the conditional lethal experiments gave you a means of saturating the genetics, that is we'll find all the ways we can of breaking this thing. You can break it this way; you can break it that way. To find out what is being broken needs some other approach. In the... the morphological mutants of phages, people found that they could just mix two extracts, so if they had one that only made heads and one that only made tails, they could just mix the two extracts and the heads and tails would glue together. I mean, that's self-assembly with a vengeance. And you could go and order all these extracts by just mixing them in the right order and seeing whether you got good phage coming out. So you could work what was an early… early step... what was a late step in assembly; did assembly branch into two parts which then united as indicated by being able to make heads and tails separately? And so you had an in vitro method of replicating the function. And that means you could study the effect of mutation on it and it would make sense. The meaning of the gene could be determined by this way. In DNA replication you could do the same thing. You could actually take an extract, see if it made DNA. If something was missing from it, you could then purify a wild-type extract, the normal extract, and see what you had to add to this to replace the missing function. In this way you could get hold of the… the protein product of the gene and characterise its biochemistry. And of course this kind of analysis really opened up the whole definition of the internal machinery of the cell.

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: Robert Edgar

Duration: 4 minutes, 42 seconds

Date story recorded: April-May 1994

Date story went live: 24 January 2008