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Dispute over the repetitive DNA in Caenorhabditis elegans


The C paradox inspires Francis Crick to ideas about regulation
Sydney Brenner Scientist
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In early '70s Francis got interested in... had been interested in some time, and we both got very interested... and he in particular after he went to a meeting, in what was called the C paradox. And this was that it appeared that higher organisms had more DNA than they should reasonably have to specify what they were doing. It used to be said that people were divided into three classes: those, there were the physicists who believed that organisms had... didn't have enough DNA to do what physicists thought were very complicated things; there were the smart molecular biologists who thought that organisms just had exactly the right amount of DNA that they needed; and there were a group of people who were really concerned with what this extra DNA was required for. And there were a lot of paradoxes in which it seemed that higher organisms were not the same as... as E. coli [Escherichia coli]. That is a lot of their RNA never got to the cytoplasm, and there was this paradox of what was called hnRNA, heavy nuclear RNA, very large molecules, most of which turned over in the nucleus. And all of these paradoxes were on trying to understand whether these were junk in a very general sense or whether they were concealing some special mechanism. Now one of the things that we discussed eternally on these blackboards in Francis's room was of course that as well as many other things. And everybody would turn up with some new theory, saying well could it be that all this extra DNA is for regulation? If so, why do you need so much? And if it's for regulation in higher organisms why don't we find it in lower organisms? Why can they get away with protein recognition of DNA and higher organisms have to have to have some special mechanism? And many of these things were written on the blackboard, of course the central part was always erased because one needed more space, but these things on the side were just left there. So that one could come in and remind oneself, there they were, my desk faced the blackboard, and I would sometimes look at it and say you know, what does this word dreams mean? Which was all that was left of some discussion. And one day Francis came in very excited, he'd been to a meeting, and he said, ‘I've got a new idea and I think that regulation must be carried out by... by single stranded nucleic acid’. So, you have the idea that higher organisms would have to do a lot of regulation, they require what is called the versatility of control. They'd have to recognise rather longer stretches of DNA, and you can't do that with a protein, this was the idea. What you would need is to have nucleic acid... nucleic acid recognition. And because you had what we would now say many, many instantiations of this, then you would have to have large areas of the gene used for control, and that was the source of why the genes seemed to be so big, why there was so much DNA. And everything was put into that, and Francis actually wrote a... he wrote a paper, which is the first time, based on the deductive method, that is, he made an axiom out of the principle of versatility and recognition, by RNA and deduced the rest of it from it. Of course that wasn't exactly fair, because he knew many of the facts, but still it was an interesting way of... of trying to work this out. At least it had the clarity that if the axiom was wrong everything else would have to be wrong, as I pointed out to him.

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: Escherichia coli, Francis Crick

Duration: 5 minutes, 13 seconds

Date story recorded: April-May 1994

Date story went live: 29 September 2010