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Choosing the nematode


Choosing an organism to study
Sydney Brenner Scientist
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I was ill one day and I asked my wife to get me a book which I'd phoned up Heffer's, the booksellers in Cambridge, which was on protozoa. I had looked at a lot of protozoa as... during my youth because I was interested in microscopy. I had cultures of paramecium on the lab bench in South Africa, and so I thought protozoa might be interesting. And I had read… I started to read very extensively – to add to my previous knowledge – over the whole of biology. I read… I read the whole textbooks of zoology, botany, followed up very specific organisms, traced very special organisms. In protozoa I had known that of course the paramecium was an object of genetic study. Tetrahymena, which was a… another protozoan, had been studied; people had started to do genetic crosses with them. And I also noted that there was a very interesting thing which, which was an organism called naegleria which underwent an… an amoeba flagellate transformation. That is, the amoeba – which crawled around on the substrate – noticed cell movement, then changed, grew a flagellum and then swam away. Of course I think we can understand that now as part of… of gamete formation. That if you have organisms that are sessile the big thing is to prevent inbreeding or for them to make gametes which can move and find other organisms to mate with. Of course, naegleria doesn't have any genetics any more, but one could argue it's a degenerate form of this. And I actually toyed with the idea that since we can propagate the amoeba indefinitely, wouldn't it be nice if, if one could then look for mutants, temperature-sensitive mutants that didn't form the flagellates? Right, then, you know, in the fullness of time we know the whole genetic system and we could then find all the genes that were involved in flagella formation. And wouldn't that be a real way to study differentiation and what turns it on in this case? And of course you had to know whether it was haploid, and that was a guess that maybe is haploid. And that was one candidate that I remember to study. Then I got very interested in cell-counting systems. I mean, how… how do things know how to count numbers of cells? You know, organs grow toward a certain size. There were many, many cases of… that you could find in the literature of; for example, I was tremendously impressed by reading in the fly sciara that… which has supernumerary chromosomes which it gets rid of in all but two cells of the 16-cell stage after cleavage. And one can ask oneself: how does it know that it's got 16 cells and that, you know, 14 minus… 14 + 2 = 16? There must be some kind of cell-counting thing. And there were lots and lots of green algae that in fact could count up cells to a certain size, and what was interesting is that some species of this closely related group had little… these little nests or colonies, if you like, which had 32 cells and some of 16. So one said, well, maybe one can find out what genes determine this, because perhaps we can get mutants of the 32s that are only 16. You know, that instead of… that count in… that can't count the last division. And a whole lot of questions like that could be seen to be exercised in this context. I… the one I was most interested... was the amoeboflagellate thing, and I found it quite common once one got reading about this. There was a little... another amoeba called hartmannella which occasionally could be induced to form flagellates, and there were a number of zoologists working on this. I visited quite a number of them to talk about this later – especially the tetrahymena geneticists – and wondered whether one could set up what was already in my mind, which had come from the… doing the genetics of temperature-sensitive mutants in bacteria where we isolated over a thousand mutants so that we would saturate everything. It was dead easy to do that. That basically: what would be the experimental conditions to try and do 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: Cambridge, South Africa

Duration: 6 minutes, 2 seconds

Date story recorded: April-May 1994

Date story went live: 24 January 2008