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Sydney Brenner and Francis Crick


'You chop off its head it regenerates it'
Lewis Wolpert Scientist
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And so, thinking about what to work on, I chose to work on Hydra, ’cause this... is a little animal and it’s remarkable. You chop off its head, it regenerates it, you take a small fragment of the animal, it’ll regenerate into a hydra. And so, I decided to work on that and I had PhD students then working on how the patterning of the Hydra actually progressed. And thinking about how the Hydra actually regenerated and thinking, made me... turn to what I called pattern formation. Now, in those days, I... so I was at King’s College... until 1966, working on Amoebae and Hydra, but in 1966 I was offered the Chair at the Middlesex Hospital Medical School to be Professor of Biology as Applied to Medicine and I went there. And in those days I thought it wasn’t appropriate for me to continue to work on Hydra, although we did go on working for the Hydra thing, because Hydra wasn’t something that medical students would be interested in and I decided that we should work on the chick limb, on the development of the chick limb instead, because this seemed to me more medically relevant. But at that time, Waddington, the very famous developmental biologist, was having a series of yearly meetings in Italy at a place called Serbelloni and very fortunately, I was invited to attend these meetings and... and that was very nice. I was slightly involved in theoretical biology, a little bit, because Danielli, my professor at King’s College, had started the Journal of Theoretical Biology and that was a major step forward and I helped him a little bit with it. It’s rather remarkable, I’m still an editor of that journal. I’m one of the three main editors of that journal still, in fact I spend... even this morning, as a matter of fact, I spent a little time doing my... doing my work on the journal.

At that time I began to think, how did the Hydra know what to do, where to make its head? And I was also struck by a very old experiment, one that goes back over 100 years, by a man called Hans Driesch. He had fertilised a sea urchin egg, he had to divide into two and then separated the two cells. So what would these two smaller cells give rise to compared... Would they give rise to half-embryos? No, they gave rise to normal, but smaller embryos — so that’s pretty remarkable — so it showed that you could get a perfectly normal embryo, half the size. How was that possible? And I began to think about pattern formation and we had discussion, ’How could this ... how could we do this?’ And then I had, I think, one of the few real flashes of insight in my scientific career; I came up with the French Flag Model and what that is, the following: what strikes me about patterning and the Driesch experiment, is that you could get the same pattern with different sizes and numbers of cells and the one pattern that is invariant with size, is the flag. If you have a French Flag that’s big or if it’s small, it’s one-third blue, one-third white, one-third red. So I came up with a model or the key to thinking about pattern formation, based on the French Flag Model. And the problem is, that how do the cells know where to make blue, white and red, irrespective of how many cells there are in the line? And I came up with the idea that the cells acquire positional information, so the cells know their position in a line and therefore they know whether to be red, white or blue. And the problem was, how is that position specified? So that was really quite a major step forward in my own thinking and I was very excited about it. And I gave a lecture... I gave this... I gave a talk at the Serbelloni meeting in... at Waddington’s Meeting in 1968 and then went to a meeting in Woods Hole in America. And there I gave one of the big Friday night lectures in 1968, and it was a disaster. No one would speak to me after the lecture; they so hated my ideas about gradients that no one would speak to me after the lecture.

Lewis Wolpert (1929-2021) CBE FRS FRSL was a developmental biologist, author, and broadcaster. He was educated at the University of Witwatersrand (BSc), Imperial College London, and at King's College London (PhD). He was Emeritus Professor of Biology as applied to medicine in the Department of Anatomy and Developmental Biology at University College London. In addition to his scientific and research publications, he wrote about his own experience of clinical depression in Malignant Sadness: The Anatomy of Depression (1999).

Listeners: Eleanor Lawrence

Eleanor Lawrence is a freelance science writer and editor, and co-author of Longman Dictionary of Environmental Science.

Tags: Middlesex Hospital Medical School, Journal of Theoretical Biology, Serbelloni, 1968, Woods Hole, USA, Conrad Hal Waddington, Jim Danielli, Hans Driesch

Duration: 4 minutes, 53 seconds

Date story recorded: April 2010

Date story went live: 14 June 2010