Charles Delisi on Mechanics of the HGP
  Charles Delisi     Biography    
Recorded: 08 Sep 2003

So starting at the department, after we had the Santa Fe—the Santa Fe workshop I was obviously able to do by myself. My budget at the time was about three hundred million dollars. So we had some resources available. We had the Santa Fe workshop. I wrote the memo based upon these forty letters. I wrote it to Al Trivelpiece. Al Trivelpiece became an immediate moral support at the very least in the sense that he spoke about it whenever he could. He argued the case to the secretary. Al was a phenomenally articulate advocate. Jim Decker who was the deputy assistant secretary was an advocate. Judy Bostock at the Office of Management and Budget became converted. I don’t know if she went around raving about it, but she was very positive about it certainly. And then finally in the Congress, Senator Domenici and the staff picked up on the idea very, very quick. And Pete thought that this was one of the few things where he could go back to his constituency and explain the importance in terms that people could understand. Explain the importance in terms of getting at diseases, particularly getting at genetic disease, but of course, getting at infections that we all know that in fact there have been well over one hundred genomes sequenced now. A lot of them related to infectious disease agents. And we had that in our original plans. When we wrote our plans in 1986, the idea of sequencing microbial genomes was part of that. We wanted to do that from the very, very beginning. So we had the support, actually we had support all the way across. We had the support from the department. We had the support from the OMB. We had the support from the Congress. NIH didn’t quite—Vince DeVita, who was the director of the cancer institute, was enthusiastic about it. I spoke with him. He was very enthusiastic about it. In fact, he sent me a letter of congratulations, saying this is great; let me know what I can do to support it. Jim Wyngaarden was proceeding more carefully as he had to because the NIH constituency is very, very complex. I mean you’ve got fifty different groups coming at your from one hundred directions. And everybody tugging in their own way. So it was a much more difficult job at NIH than we had at DOE. DOE did not have a lot of—on the other hand, we didn’t have the support constituency either. I mean NIH, nobody wants to die, so everybody’s out to cure disease. DOE didn’t have—not only didn’t DOE have a constituency in the health sciences, but in fact the agency looks like to many people an arm of the defense department. So there was a natural hostility to DOE. In fact, you know, what are you doing? You must have some defense reason for wanting to do this. I mean I’m sort of a liberal democrat working in a republican administration, so the last thing on my mind. So DOE had no natural constituency, but on the other hand it wasn’t encumbered by, for the same reason, fifty different groups tugging at us in many, many different directions. So we had somewhat in that sense an advantage. I had flexibility with the budget. We were able to move this along very, very quickly. NIH couldn’t.

So we had a line item come the end of the summer of ’86, we put in for the presidential budget submission which was going to be in January, we got a line item which survived the department and survived the Office of Management and Budget. And it was in President Reagan’s budget submission for; I guess it was ’87, for the human genome project. So we had the line item. NIH did not. But Jim Watson then lobbied Congress. And I don’t know, and he and someone else, I don’t know who the other person was that he took along with him. But he got money into the NIH budget. So the next year there was money both in the DOE budget, about twelve million, and money, about sixteen million in the NIH budget. And that’s how the thing got off the ground. Still the political situation with constituencies was still not settled. There was still a lot of debate in the community. There was still fear that this was going to upset the nature of NIH funding, and in fact as late as 1990, there were letters going around urging the community to bring this to a halt. I thought it was settled by that time. I thought it was settled long before. I had left DOE feeling that this thing was going. But there was still that residual problem largely because people didn’t—partly because people didn’t understand it, and part because there’s always some natural resistance. There are going to be losers involved in this. I don’t think there has been any losers involved in it. I think the amount of money—first of all, even if it were zero sum situations, the amount of percentage of the budget is inconsequential essentially of the NIH budget, of the DOE budget.

But what helped us in the ‘90s, I mean it’s quite true that this need never have happened. I mean I was a little bit “Pollyanish” when I left, and I felt and was sure that the time had come. But looking back, a good part of the reason that it went so well and so rapidly and so successfully was the economy. That we had a particularly—well, in fact, I don’t think there’s ever been a time in my life that I can remember when the economy was as good as it was in the mid-90s, at a very, very crucial time for this project. If the economy had turned down, it’s quite possible that this thing wouldn’t have been finished for another decade. It’s very, very possible, in fact.

Well, this was what the chairman of the academy told me. That the community, certainly the academy proposal would throw the support behind the Department of Energy doing it because they wanted it done. They thought it had to be done. So it was either going to be done with NIH and DOE and with a major with NIH. Or if wasn’t going to be done by NIH, then they felt very strongly that it needed to be done and the only agency that remained to do it was DOE. Then they were going to support the Department of Energy, and we would have done it at the Department of energy by itself.

I think that would have done been less viable. It would have been very difficult for the Department of Energy to carry this out the way it was carried out, and I think it was very important that it did develop the way that it developed. But it didn’t happen very, very easily. We had a lot of education to do at the beginning. We had the administration, we had the Office of Management and Budget, we had the Congress, and we had the whole good fraction of the community to convince that this was worthwhile. So the whole process of converting that a few people initially wanted into policy, into national policy is a very, very complex process. There’s a whole community involved, it’s not just something where you appropriate ten million dollars and all of a sudden you have a workshop and the next thing that happens is that it’s happened. It doesn’t happen quite that easily.

So the sequence went: Bob Sinsheimer’s meeting in the spring of 1985, I think if May of ’85. That had an influence on me. I found out about it. When I found about that meeting, that I realized that there were other people that thought it made sense to sequence the human genome. So that was important. That was important precursor to the Santa Fe meeting in the sense that it really made me a little more optimistic that the culture could—the cultural barrier could be breached. It could be over come. There were people who understood what computers were about. The role computation had to play which was going to be essential. There would be no genomics without computers and without computation. And there were people in the community who understood that, and believe me, there were not a whole lot of them because I spent my life doing this and trying to communicate with people. So that was very important. That was an important link.

The Sinsheimer to the Santa Fe meeting were clearly linked. I don’t know that there was a link—that Cold Spring Harbor meeting which happened, I think, in June, three months after the Santa Fe meeting. David Smith from my office attended that. And there was a serious debate. And I think Botstein and Gilbert were at opposite ends of the issue there about it. And I think that was an important meeting in that it got a lot of the leaders thinking. Some of them had already been at the Santa Fe institute meeting. So that I think that really built on a momentum. And it was a very important meeting. Most of them were NIH constituents and then those constituents who became interested played a role, some of the important ones anyway, played a role in getting that National Academy study done which was important—it wasn’t important for DOE because DOE was already involved in it, but more important for getting NIH involved in it. And I don’t really know the history of that Cold Spring Harbor meeting. That is, I don’t know what motivated it, and how it came about. But it was clearly important in that it stimulated, it impacted a good part of the NIH constituency.

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.