Michael Ashburner on Early Research on Gene Regulation
  Michael Ashburner     Biography    
Recorded: 31 May 2003

When I got back to my postdoc—I was a postdoc in Cal Tech—and I got back to Cambridge. I had a junior faculty position in Cambridge at the time. I got very interested in the problem of how the activities of genes are controlled over time during development. And this at a time when messenger RNA had just been discovered. But we really knew very little about the fundamental aspects of eukaryotic molecular biology. But I was working with a system in drosophila which had been discovered many years before in which you could visualize gene activity because of changes in chromosome morphology called puffs. And these puffs which had been proposed by Michael Berman in a paper actually in the 1956 symposium, a very important paper by Wolfgang Berman. Berman had proposed that these puffs which you could see in a microscope where active genes. And I had spent quite a time writing my thesis and later at Cal Tech looking at the way these patterns of these genes are active to change over time during development, and in a very descriptive way. And then when I got back from Cal Tech to Cambridge in early 1969, I started working on this experimentally to see what actually controlled this. And we worked with a hormone hydroxyecdysone. And I spent initially by myself and then with a student called Jeff Richards trying to work out just how a very complex temporal program was controlled by this hormone. And it turned out that this hormone was essentially a trigger that you could start the process and then it was self run. And I was invited to the 1973 symposium and I decided to talk on this. And Jeff Richards, who was my graduate student and I had a huge amount of data which we hadn’t really sat down and really thought about very deeply. But it was the impetus of having to write a manuscript for the 1973 symposium which actually forced us to go into a period of six weeks of very, very intense intellectual effort to actually come up with a formal model for this which we published in that symposium in 1973. And remarkably that model is correct. This was before transcription factors when we could really characterize them, and before any hormone receptors had been characterized. Maybe one of the progesterone receptors had been done by then, but basically these things were very perceptual. And it took a long time, but eventually David Hogness’s lab in Stanford started to characterize at the molecular level, characterize these genes which we were looking at and show directly that we really did encode transcription factors just as we had proposed back in 1973.

So I think that in one way—partly because I was doing the experiments myself and thinking about it myself, which sadly in the last ten years I haven’t done. I’ve just been working with computers and the telephones. And it makes the lab because it really had been forced because of this rule when you come to a symposium you must turn up with your manuscript in hand for the symposium volume, which when I was young I took very seriously. So we were forced by having to write that paper to actually develop our ideas. Otherwise we might have gone on, the problem is doing experiments was too much fun to stop and think about it. Good exercise.

Michael Ashburner, a leader in Drosophila Genetics and bioinformatics, received his B.A. (1964), M.A. (1968), Ph.D. (1968) and Sc.D. (1978) from the University of Cambridge, where he is currently professor of Biology in the Department of Genetics and a Professional Fellow of Churchill College.

He has been the joint head of European Bioinformatics Institute (EBI), of the European Molecular Biology Laboratory (EMBL) and was co-founder of Flybase, the primary online database for Drosophila genetics and molecular biology, the Gene Ontology Consortium, an effort to coordinate biological databases through a defined taxonomy of gene function, and the Crete Meetings, a bi-annual event focusing on the developmental and molecular biology of Drosophila melanogaster.

Among many honors, he is the recipient of the G.J. Mendel Medal (Czech Republic 1998) and the George W. Beadle Medal (Genetics Society of America 1999).

Michael Ashburner