Recorded: 08 Sep 2003
So about 1985, I got a call asking me if I was interested in heading the health and environmental research programs at the Department of Energy. I had been at NIH for about ten years then. I was very happy there and working very productively. And I thought about it and wound up speaking to Al Trivelpiece who was then the assistant secretary for energy research, and decided to take that position. I knew something about the national labs because I had been at Los Alamos for three years, so I didn’t feel that I had a terrific learning curve. But I really did not know a lot about the type of work other than GenBank which was at Los Alamos, and the chromosome library project, the cell sorting activities to separate chromosomes. I didn’t really know a whole lot about the DOE programs and certainly in the environment I knew very little.
In any case, I went over and found very quickly that one of the major problems there was to assess the damage to humans and the environment done by low levels of anything; low levels of toxin, low levels of radiation, any type of toxin. How do you assess that? There’s enormous polymorphism in the human population. How do you grapple with human polymorphism? I mean at high levels this affects everybody, but at low levels different people respond in different ways. It’s a question of how you grapple with that.
Well, one way to do it would be if we had a reference sequence of the human genome, and we knew at the time by comparing chromosomes in the same individual, that your DNA, my DNA differ by about one base in one thousand. We knew that, so it seemed to me if we had a reference genome, we could then do differential sequencing. Of course, the technology for that wasn’t available at the time for differential sequencing. But it we had it, I suspect that the technology would become available, that we could begin to grapple with the problem of human polymorphism. But I had already ruled out, I mean I had already thought three years earlier that we weren’t going to do this because the culture wasn’t there, but I rethought it. And I think what made me rethink it, what really jogged me was the OTA report. This is a report by the Office of Technology Assessment which was placed on my desk one evening by David Smith, he had no idea of what was going on. And it was an assessment of heritable mutations. And at DOE, Mort Mendelson had chaired that Office of Technology Advisory Committee. And in that there was some talk about whole genome sequencing. And that made me think that maybe this wasn’t such a crazy idea. There were other people in the world thinking about it. I actually didn’t know who was thinking about it. Who wasn’t thinking about it? And since my own work was met with such polite indifference, I figured biologists thought this was really way out.
So, the OTA Report on Heritable Mutations jogged me because I realized for the first time that there were other people in the world thinking about whole genome sequences, and in particular, some of the major biological leaders [such as] Lee Hood, Walter Gilbert, Charles Cantor were thinking about these things. So I realized that I wasn’t alone. And that the idea of sequencing the genome, the human genome, wasn’t totally out of the question. It wasn’t totally ridiculous.
And that led me to call Mort Mendelson, who was then the head of our advisory panel, and ask him if he knew anything about what was going on; who was interested and what had happened. And he told me that Robert Sinsheimer had a meeting, this as in October ’85 that I called him, and Sinsheimer’s meeting I think was in May ’85. It was in the spring.
He told me that there was a meeting. He told me what went on at the meeting and I got increasingly excited. And then he concluded by saying, “and it’s a stupid idea.” He said that he thought mapping was a smart thing to do, but sequencing all the human genome was crazy. So, of course, that didn’t, I decided I wanted to get handle on, a little more extensively on what the feeling of the scientific community was.
A year and a half, two years we actually did quite a lot in a fairly brief period of time. So I was with DOE heading their health and environmental research programs form 1985 to 1987. I started this almost immediately after arriving and by the time I left and as I was leaving I know a number of people said, aren’t you worried? You’re leaving and this thing is not going to continue without you. And I said, no, this has a life of it’s own at this point. It’s going to go spontaneously. I was probably overly optimistic, I think, because the main thing that could have gone wrong, as I mentioned before is the economy. That was the big stochastic factor in my mind, how that was going to play out. My assumptions were under normal economic conditions this was going to happen without too much of a problem. The economic conditions were spectacular. They could have been bad and then we would—this would have gone on for at least another decade.
Charles DeLisi did pioneering work in theoretical and mathematical immunology. He received his Ph.D. in physics and did postdoctoral studies in the chemistry department at Yale University researching RNA structure. He became a theoretical physicist at Los Alamos National Laboratory and then moved to the National Institute of Health, where he worked on molecular and cell immunology for ten years.
DeLisi is currently director of the Biomolecular Systems Laboratory, Chair of the Bioinformatics Program, Metcalf Professor of Science and Engineering and Dean Emeritus of the College of Engineering at Boston University.
Charles DeLisi develops computational methods for high throughput genomic and proteomic analysis. His laboratory is helping to develop technologies for fingerprinting the complete molecular state of a cell. He is interested in finding computational methods for determining protein function and researches the structural basis of signal translation by membrane bound receptors, the structural basis of voltage gating, and the docking of peptide hormones and neurotransmitters at their sites of action.
In 1986, DeLisi and Watson met at a CSHL meeting and spoke about their interests in sequencing the human genome.