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Genes make proteins, but what for?
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One of the projects that we were very interested in was how do you make patterns in biological systems. And Peter Lawrence, who was one of the younger people that joined our lab, was working on, essentially, gradient definition things, and had been working on bugs, Rhodnius bug and transplanting bits of skin and showing that what has happened influences, its neighbours influence it. And I can remember that one of the things to try and explain the difference between the two styles of development, because I was someone who — working with a nematode, which has a fixed number of cells and which it appears everything is kind of counted out — had a very different view of things from people who were working with Drosophila or many of the other embryological systems who had adaptive systems, regulatory systems, if they cut out a piece, it was sometimes replaced by what is there. So that I had invented a little way of explaining the difference between the system that I saw it, in the nematode and the system that of course was more likely in embryology. And of course when you have two parties like this, an extreme left and an extreme right, the safest thing is to be a liberal and say well, I think it'll be a bit of both. And actually I think the liberals have won in this argument of how patterns are made biologically. It is a bit of both. And the… the example that I gave is I used to call the European plan versus the American plan. And I said that in Europe was the most... you don't give a damn who your neighbours are and where you live, the most important thing is who were your ancestors, because if you are, you know, the second great granddaughter of the first daughter of so-and-so, this gives you your exact position in the hierarchy. And so that was a thing in which you had a computation which depended on lineage. And I use the word computation very emphatically, because what you are arguing by this is what's going on in those cells, is that they are always asking themselves the question, who am I? And what you have to examine is your lineage, and you are what you are because this is the way you got there. You are... you are the first division of the second division of the third division of such-and-such a cell. And so I would say that's a lineage computation of faith... of fate. As opposed to what I call the American plan, which is you don't give a damn who your ancestors are, what's most important is who are your neighbours. And that's true in America, because if all your neighbours are dentists, that for example, tells you your social class in America, whereas if they're all... if they're all truck drivers, that's a different kind of person that you'll be. And this I called the spatial computation. That is, if you wish to know what you are, you investigated who your neighbours were. Now, of course you can't do that consciously, but cells would then receive signals from other cells that would say, you know, you are occupying this position, therefore turn on these genes, etc. etc. And that is what Lewis Wolpert referred to as a positional gradient. Now, you have to be very careful in this to distinguish between a computation... depends on... which depends on position, which is, I would call, a spatial computation, and simply a thing that just says you are there, so that's what you are. That is positional information may just be not the cause of anything, but the outcome of something else. And of course that's true in all of embryology, is to really worry about cause. And one of the things that's disappeared in modern science is of course the concept of causality, and there's still a lot of confusion over the fact that people, if B follows A, they immediately think that A is the cause of B, but you have to decide that by another experiment.
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.
Title: Lineage and special computation: European plan vs American plan
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.
Duration: 5 minutes, 12 seconds
Date story recorded: April-May 1994
Date story went live: 29 September 2010