Recorded: 08 Sep 2003
Well we, of course, DOE headquarters sponsored the workshop. I wrote a memo to Mark asking a series of questions that I wanted addressed at the workshop. And then I asked him to get letters from the attendees. In fact, I showed that list of people who attended and who sent—I still have those letters in my files from about forty of them or so, summarizing their thoughts. Those all came back to me. I read them and I still remember Tuesday afternoon in Washington going through these letters, reading them and then I wrote a memo to the assistant secretary, Al Trivelpiece, outlining an idea for the project; saying that it had to be done in stages, that we couldn’t just go out and sequence. That we first going to develop methodology. We were going to do mapping, physical mapping in particular. We were going to develop methods for sequencing because we couldn’t deal with the methods. And then once we had the maps and once we had the methods, we could go on and do the sequencing. So it was a three phase project that I outlined in this memo.
That basically convinced Al Trivelpiece that it was a worthwhile thing. How much money we were going to get—DOE is, it’s a funny situation, because it is a physics organization. And it’s very hard for biological, environmental science to get a lot of money. So I had to convince the department. I had to convince the secretary. I had to convince the Office of Management and Budget, which was notorious for slashing budgets. And, in fact, I was told when I took the job at DOE, and I spoke to some congressional staffers at that time and I was told, don’t expect any changes in your budget. We’re not going to fund, you know, you’re not going to get more money. So I knew I was in for a hard time. The department, OMB, and then I had Congress to deal with. And I actually it turned out so in the whole process, OMB was very helpful it turns out. I went to OMB expecting them, I didn’t know what I was expecting. But I wasn’t expecting them to be helpful. What they liked about it is that it was a well-defined project. It had a beginning, a middle and an end. It was an engineering project. It was presented as an engineering project, and it is an engineering project.
And you know the other criticism, the community was furious about this. And I think the concern was that it was, particularly at NIH, that it was going to cut into the way things were done. It was going to shift money from all RO1s, from investigator initiated research to big projects. It was going to politicize science, and the result is there was a lot of resistance.
So, OMB was behind it. I don’t know if they were ready to give big money, but they were behind it. And they said, you know, you’ve got to go out and you’ve got to convince the community basically that this is something worth doing. So I spent a lot of time preparing lectures, and giving lectures. I had no doubt actually after the first couple of meetings, the Santa Fe meeting and the subsequent meetings, that this was going to happen. It was clear to me in the letters I was getting from all over the world. It was clear to me that the underlying sense was there. That it was technologically feasible. That the budget wasn’t at all ridiculous because it was going to save us tens of billions, or hundreds of billions of dollars if we created this resource. It was all about creating a resource.
There was a lot of misunderstanding. I mean, part of it was the misunderstanding of the value of a reference sequence. Part of it was the misunderstanding that this was not science that was being proposed. I mean, people would say, but this isn’t science. And I would say, of course, it’s not science. We’re talking about developing the infrastructure for science. And that’s something that, in effect, NIH wasn’t used to doing. Their review system wasn’t set up to handle that type of thing. It was set up to handle hypothesis driven research. So that concept, the sociology which I was concerned about from the beginning was an obstacle in getting across the idea that we’re not proposing science, we’re not proposing hypothesis, we’re proposing to develop an infrastructure that would make 21st science do-able in a way it needed to be done. That we would be able to get out the really interesting questions of biology, which are the questions of diversity. The questions of complexity that we would be able to begin to consider the cell as a system, and not spend all our time on one protein or one gene but begin to understand the way proteins and genes interacted. All that needed the right type of infrastructure. And that’s what the shift was all about. So we’re really basically talking about a shift in the way that science is done; going to high-throughput biology. It still remains hypothesis driven, but now we’re able to really develop meaningful hypothesis because any biologically meaningful hypothesis had to consider the system. It can’t consider just an individual. Its function is, in fact, system wide.
Yeah, in 1985 I think there were several groups of people with different attitude towards this. There was a small group that wanted to see this happen. A group of the major, the very senior people in the community; Walter Gilbert was strongly in favor of it, Lee Hood was strongly in favor of it, Charles Cantor, Bob Sinsheimer, of course. After that workshop, I know Robert Sinsheimer made a number of attempts to get the agencies to get the NIH involved, and there wasn’t much of a response. And I think there was a general feeling at the time that this wasn’t going to happen. And one of the reasons I think that is sort of an interesting story.
I wanted to, after I read the OTA report and spoke with Mort Mendelson, I decided to put together a small advisory group on the genome. This was probably at the end of ’85, the beginning of ’86 and I asked someone from my organization to ask Walter Gilbert if he would be willing to be on it. And the answer was no. And I asked her why he said no. And he said, I don’t want to spin wheels, basically this is never going to happen. So the problem confronting these people at the time, some of the senior leaders who wanted this to happen was how do you convert what you’d like to happen into policy. How do you convert it into national policy? And there didn’t seem to be an easy way to do that. They were trying to do it. There wasn’t very much of a response. And the pervasive feeling was that this just wasn’t going to happen very easily. And so that’s what you see reflected in Walter Gilbert’s invitation to be on our advisory committee. He was an extremely articulate advocate of the genome project, but I believe he felt at the time and certainly in ’85, that nothing much was going to happen in a way of a formal government program.
And then when I had to have the Santa Fe workshop, there was a great deal of enthusiasm. I invited NIH representatives to come. They didn’t attend for whatever reason. I spoke with both Ruth Kerstein and Vince DeVita. Ruth was the director of general medical sciences and Vince DeVita was head of the cancer institute DeVita was very interested, but couldn't get involved directly. He said he would help in any way that he could. Ruth Kerstein was very concerned about the constituency. General medical science at the time tended to fund RO1 investigator initiated grants. And there was a legitimate concern that this was going to seriously upset the way science was funded, so there was hesitancy there. As a result hesitancy from Jim Wyngaarden who was the director for the same reason.
I think a lot of people, David Baltimore was very opposed to the project probably because DOE was involved, but I think more fundamentally because he was worried that it was going to politicize the scientific process, just as NASA is politicized in my ways. And he felt that the system was functioning very well as it was. So he was opposed to it. On the other hand a good part of the NIH constituency; Gilbert, Hood, Cantor others who were paid by NIH were in favor and wanted to see NIH get involved. I wanted to see NIH get involved because I thought it was a natural agency.
Ultimately that sort of interest by a lot of important geneticists who were funded by NIH, that interested in seeing this happen; Victor McKusick was obviously very interested in seeing it happen, resulted in a National Academy study. And that National Academy study wound up supporting the idea of doing a genome project. The report was handed to Jim Wyngaarden and he was told at the time that if NIH wasn’t going to do it, then they were going to support DOE and try to get as much money as it necessary in to the department of energy to have it done there.
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.