Leroy Hood on Research Highlights: Developing Automated Sequencing
  Leroy Hood     Biography    
Recorded: 29 May 2003

Well, I would really say two things; developing the automated DNA sequencer which made the human genome project possible obviously in many ways was the most important thing we did vis-à-vis to the genome project. But I think second it was being involved in the very early days in exploring what large scale DNA sequencing was really going to tell us about biology. I mean we never made our center a very big center because I’ve always been much more involved in biology than in just turning out sequence data. So we focused on regions that had biological interests and what was enormously exciting was to learn how much one could come to understand about this digital language of our chromosomes and from that it’s really taken me very directly into my current passion which is this thing called systems biology which is really studying systems from the point of view of looking at how all of the elements behave rather than looking at things one or two at a type. So, and, I think this largely is a consequence of the genome project and [will] be the dominant theme in biology over the next fifty years.

It came about not as a Eureka! moment, but as a fundamental philosophy in how to do science. So I went to Caltech in 1970 and I determined then that I would spend half of my time doing technology development, and half my time doing biology. And that was really an unpopular point of view at that point in time. And the essence of doing the technology development was the idea that technology should be driven by the needs of biology. That is what you wanted to do in developing new technologies is kind of open up frontiers in biology where you can explore in new and different ways biological information.

But what was also obvious [is that] once you developed a new technology then you’d have the potential to revolutionize biology. So I—we rationally thought about what are the things that we can develop that would really fall into that category. So the first thing we did was to develop a highly sensitive protein sequencer. The second thing we did was to develop the world’s first really effective DNA synthesizer. And that was followed by a protein synthesizer. And the most difficult technically by far of those instruments was the fluorescent DNA sequencer. But they were one of a family that we logically thought about in the seventies that we wanted to do. And we methodically went about it. So when Sanger came up with his method for DNA sequencing. And Gilbert and Maxam came out with their method in ’77, whenever it was. It was clear that one of those two strategies was the one that was really going to have to be automated. And for interesting technical reasons we choose initially in about ’79 to start working on the wrong one. We tried to automate Maxam-Gilbert. And then in about ’82 or ’83 we actually hit upon the right idea. And that actually was really an eureka moment because I remember at one point in time when afternoon three or four of us being together and kind of laying out all the basic requirements of what we had to do to automate the Sanger method for sequencing. And then it was another three or four years before we were able to transform that very clear vision of how to do it into reality because we had to bring into the laboratory computer scientist and engineers and chemists as well as biologists just to kind put this whole thing together.

But the idea for sequencing was a derivative of this philosophy that biology and the needs of biology have to drive the kind of technology that’s developed.

I think what was really interesting is when we started thinking and talking about this in the late ‘70s, enormous numbers of people were skeptical about, you know, how are we ever going to need to sequence that? I mean graduate students can sequence it. We don’t need machines to sequence it. But I heard that for the DNA synthesizer. I heard it for peptide synthesis. And the striking things about technology is “provide it and they’ll come.” People will think about wonderful ways to use it if you transform how people can look at and do and carry out biological—the task of deciphering biological information.

Leroy Hood, a leading scientist in molecular biotechnology and genomics, received his M.D. from Johns Hopkins Medical School (1964) and his Ph.D. in biochemistry from Caltech (1968). In 1992, after more than 20 years as a faculty member at Caltech, where he and his colleagues revolutionized genomics by developing automated DNA sequencing, he relocated to the University of Washington to establish the cross-disciplinary Department of Molecular Biotechnology.

Dr. Hood is currently President of the Institute for Systems Biology in Seattle where he leads efforts to pioneer systems approaches to biology and medicine. He is a member of the National Academy of Sciences and has received the Lasker Award for his studies on the mechanism of immune diversity.

Sharing an interest in the study of antibody diversity, Hood and Watson met in 1967 when Hood attended his first meeting at CSHL. Leroy has been working on the genome since the late 70’s. He went to the first official genome meeting in Santa Cruz in 1985 and has attended all of the subsequent meetings which have been held at Cold Spring Harbor Laboratory.