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Inside-out genetics gives faster results


Molecular Genetics and gene cloning
Sydney Brenner Scientist
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Well, the early molecular biology, the early molecular genetics, was really the science for a young man, because... and I really enjoyed it. And C. elegans (Caenorhabditis elegans) was... was a science that fitted by mature middle years, because it had a huge strategic component. That is, it wasn't something that you could go into the lab and do an experiment and get the answer the next day, but really needed the development of a... a lot of... techniques and a whole range of what I would call normal science. I mean, bringing the science of observation back to biology and getting the system into a form where in fact it could reap the benefits of the gene cloning that had been discovered about half way through its... its course. And so for twenty years, until the ‘80s, that is what I worked in, and I had spent...

[Q] I just want to interrupt one tiny thing there. I have a feeling that you're slightly bored with this. Although you've created this enormous industry, hundreds of laboratories, if I'm allowed to comment, I don't get the feeling that you're interested in it at all. Could you say it, Sydney, it's just so peculiar?

Well, I think the... in... during the course of the work on C. elegans, we had tackled the molecular questions. Starting at the begin... at the beginning of the ‘70s. And of course the thing that came along and made it the subject was of course gene cloning. And that is what we turned our attention to, and that of course has been the answer to all of developmental biology, that you find out how the gene works by cloning it and looking up its sequence in a database and seeing if anybody's got anything like this before. And then you can take comfort in each other's ignorance, if you like. However, once that had gone forward and once it became clear that other people could do this probably better than I could, that is, I felt very much that my role in this had... had been completed. And therefore it could be safely left in the hands of the children, so to speak, and I could go off and do other things. And the... I was very heavily involved in being the director of the lab and spending my time doing the accounts and trying to sort out budgets — really a total waste of time in my opinion — and I think it was the biggest mistake I ever made. However, what I came to realise now is that we had a new way of doing genetics. And that therefore instead of... of denying it, as many people thought... wanted to do, this was just going to be a whole new science, and if it was going to be a whole new science I want to be in it at the beginning. Now one of these was... there was this new way of doing genetics. The idea which was simply stated at the time when all of this came, is, let's go and get the whole sequence of a genome. Molecular genetics, if you like, classical molecular genetics was an extremely difficult way of reading the sequence of DNA. Now that we could do it directly, let's go and do it. And in principle we just have access to the total DNA. And that is what cloning DNA and sequencing it could give you. Therefore the classic approach to genetics could now take on a different... a different guise and what I thought immediately was it needs to be conducted with the same logic. And if you ask what does a geneticist want to know? He wants to know what are the genes? What do they do? How many do we have? How do they map onto phenotypic function? And how does he do this? Well, in classical genetics he collects mutants, because it is a paradigm of... it is the case of classical genetics that you cannot assert the existence of a wild-type gene, that is a gene performing a normal function, until you have a mutation, a deviant of it. Once you have the deviant, that proves there must be something. In other words, you cannot say there is a gene for... that makes plants tall until you find dwarf mutants, that is, until you find something that suffers from lack of tallness. And indeed that is the whole of genetics, that is, you must find something that suffers from the lack of the function you are doing. You are doing surgery at the genetic level.


Listeners: Lewis Wolpert




Listen to Lewis Wolpert at Web of Stories



Tags: Caenorhabditis elegans

Duration: 5 minutes, 58 seconds

Date story recorded: April-May 1994

Date story went live: 29 September 2010