And so I wound up majoring in physics, and got my Ph.D in physics. I postdoced—at Yale, I decided as a graduate student, I got interested in biology again, of the idea of applying physics to biology. Thought I had to learn some chemistry, so I spent three years at Yale as a postdoc in the chemistry department. And then, ironically, in my first position was in the theoretical division at Los Alamos, that they hired me as a theorist, a theoretical physicist. And it was there that I met George Bell, who is this theoretical physicist, who had been interested in immunology and, in fact, did some of the pioneering work in theoretical and mathematical immunology. And we did work, in fact, with the Russians at that time. With Gryuri Marchick, who is the vice-president of the Soviet Academy of Sciences. And he had arranged some international—because he got interested in mathematical immunology also. So the whole gang of us were interested in immunology.

And I did that, I was at Los Alamos for three years and my work caught the attention of some people at NIH. I wound up going there, first on leave as a visiting scientist, and then I was offered tenure there rather early on. So I was at NIH for ten years. And I was doing mostly immunology, immunologically related work; mostly modeling, mathematical modeling.

So I went to NIH. I did a fair amount of work on cellular immunology, cellular and molecular immunology. Was following though, when I postdoced, I worked on RNA structure and developed some of the early methods for calculating the structure of RNA, which at that point, I think sequencing was a big deal. One had some RNA sequences, that’s what you used to sequence at that time and try to get the DNA by going backwards.

So I was developing methods to calculate secondary structure of RNA ____free energies basically. And I kept on following what was happening. I was working in immunology, but I was following molecular biology. And in the early ‘80s, I looked at the way sequencing was going. It was clear that there was an explosion. And it seemed to me that there was soon going to be a time when it was not going to be easy to assimilate that data just by experimental methods alone. That we needed to start developing computational methods. And so I started working on methods to do things like identify exon-intron boundaries computationally. That was pretty much—there were a handful of people in the world at that time who were thinking about such things. I published a few papers, started developing—we developed, we, I mean myself and Minoru Kanehisa who was a senior staff fellow with me at the time. Manura is now back in Japan where he heads the Japanese—he has the largest bioinformatics program in Japan.

He developed actually the first relational database system. That was in my laboratory at NIH, which system of DNA sequences, protein sequences and structure and protein structure. And we started beginning to develop software to analyze those; to analyze DNA for functionally interesting sites. We developed methods to functionally classify proteins based upon sequence motifs, not based upon sequence itself. But I think those were the first attempts to use motifs.

Anyway, that worked. There weren’t many people doing things of that sort. I spoke on it a—published a few papers, a half a dozen or so, spoke on it at a few places. It was met with a lot of indifference, very polite indifference. I think it was pretty much people weren’t, molecular biologists weren’t ready for that. And I basically decided it was a little bit embarrassing to talk about it. So I didn’t speak a whole lot. I spoke once or twice and didn’t say much about it. What we were interested as I looked at the rate of growth of DNA, you couldn’t help wondering, are we ever going to be able to get the whole human genome. Is that going to happen in our lifetime? Are we going to be able to get all three billion or so bases?

And I thought when I was at NIH, I thought that it wasn’t going to happen. And I thought, not that it couldn’t be done technically, I had no doubt that we could do it technically, but I thought it wouldn’t happen because the cultural shift was going to be too large. Biology wasn’t used to doing—this was a large scale project, and it just wouldn’t happen readily because the culture wasn’t there to do that type of research.

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.