Recorded: 09 Apr 2001
At Harvard, I was following Jim’s intuition. Jim had written in The Molecular Biology of the Gene how he thought development worked, mechanistically, involving RNA polymerase, sequential changes in gene expression and transcription, and the alteration of the specificity of the enzyme RNA polymerase, by adding new specificity: sigma factors at different stages. This is in the first edition of his book. There were no data supporting those statements at that point. I came into the lab at a point when a number of people were attempting to see if indeed this was the case.
And my project was, in fact, focused on that basic issue. And it turned out to be pretty much the case. Some detail differences, but the essence of the idea and the way in which transcription is at the heart of many developmental changes, such as gene expression, have become very popular these days with arrays looking at everything at one time, different times and so on and so forth. All of that was pretty new then and how it would be controlled and the idea of using a core enzyme that might have a different factor was really very new. [It gets] a little more complicated. It depends upon what organism you are looking at. But basically much of the thinking was very much on target, and that’s what I wanted to do.
So, my responsibility was to look at E. coli which was easy to study, and a particular bacteriophage, T4, and ask the question in T4-infected E. coli: what happens to the RNA polymerase as a function of time? It was clear at that point that there were changes in transcriptional specificity. There was some evidence from other people working in the laboratory, that there were changes in terms of the specificity of the RNA polymerase itself. And so I purified the enzyme and looked to see what was associated with it and in fact found some new subunits encoded by T4 genes that had been shown genetically to be necessary for the changed transcriptional specificity that occurred later. So basically I found there wasn’t just one gene, there were two, maybe even more, but the basic idea was very much on track.
H. Robert Horvitz received his Ph.D. in 1974 from Harvard University, under the tutelage of Jim Watson. He joined the MIT Department of Biology faculty in 1978, and was named David Koch Professor of Biology in 2000. He is also Investigator at the Howard Hughes Medical Institute and was appointed Investigator at the McGovern Institute in 2001.
Horvitz is a member of the U.S. National Academy of Sciences and a recipient of the Gairdner Foundation International Award, the Alfred P. Sloan, Jr. Prize from the General Motors Cancer Research Foundation and the Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience. In 2002, he was award the Nobel Prize in Physiology and Medicine with Sydney Brenner and John Sulston “for their discoveries concerning 'genetic regulation of organ development and programmed cell death'."
Horvitz currently studies how genes control the development of the nervous system and how the nervous system controls behavior. He has elucidated a molecular genetic pathway for programmed cell death (apoptosis), which is fundamental to nervous system development in all animals.