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Another hypothesis: base additions and deletions


Internal suppressors: the Theory of Mutagenesis
Sydney Brenner Scientist
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Of course, at the same time we were doing all of this genetic work and round about then we… Francis had started to play around in the lab with mutants. And his idea was he would look at internal suppressors of these mutants. Now, for example, one thing he proposed to test by this method was the following: that the message was read off the DNA as follows, it went up one chain and then came down the other chain, you see. That would mean, if you got a mutation, it would affect a protein here – OK – but you could compensate for it by mutation in a completely different place. So he was trying to ask whether there was some kind of interaction. And his first mutants didn't give him much joy; he started with a few of the base analogue ones. By the way, Dick Feynman started to do similar experiments in Cal Tech, looking for these internal suppressors and probably discovered the same phenomena. Now, where Francis found there were innumerable suppressors was with the acriflavine mutants. So you could start with a mutant, you could get changes that compensated for it, right, and this became now very difficult to explain all this very complex set of relationships, by something that interacted at the protein level – although you couldn't exclude it, say. We all knew that it was possible to get a mutation here which would alter a protein and then we would get another mutation elsewhere which corrects it. It's called an internal suppressor. But not with a kind of extent. Now, we also were labouring under this terrible... paradox, and it's always these paradox that, you know, you… you have to keep on coming back… how can… how can these two things exist and not be explained, you know? And of course we all know what I call Occam's Broom hypothesis, or Occam's Brush in America, which is that hypothesis of which the minimum number of facts have to be swept up under the carpet in order to have a consistent theory. Now, what had happened was that Freese, or Freese I should call him, had given an explanation which was roughly the following: In the DNA we can look at two kinds of changes. One of these we'll call transitions; and that is where we say a purine... one purine goes to the other purine, or, which is equivalent, one pyrimidine goes to the other pyrimidine. So cytosine to thymine is a transition, as is guanine to adenine. And then we talk about transversions, where a purine goes to a pyrimidine, and of course there are two kinds of… several kinds of transversions. Well, what Freese had come to the conclusion was the two orthogonal sets of mutants – that is, the set of base analogue mutants which were revertible by base analogues, and the set of now acridine mutants which were not – that one could be transversions and one could be transitions. Right. That was that theory of mutagenesis, as it was called. But if that were the case, you know, we had another paradox all mapped at the same… all mapped at different positions, and you would effectively expect this.

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: Cal Tech, Francis Crick, Richard Feynman, E Freese

Duration: 4 minutes, 8 seconds

Date story recorded: April-May 1994

Date story went live: 24 January 2008