 Biology was going to drive the kinds of technologies that we would develop. Well the ultimate of this would be the human genome. Could this be done? This is a major science project. It will have lots of implications. To find out how to cure most of the tremendous maladies of humankind. Mapping and sequencing the human genome would require a huge project. Now the Department of Energy was accustomed to such projects and it was ready to sign on right away. But biologists in the United States who tended to work in a kind of cottage industry were highly resistant to anything that smacked a big organization, major goals and high technology. So they opposed the project. Nevertheless, Robert Sinsheimer, who was then the Chancellor at the University of California, Santa Cruz thought it was worthwhile at least to consider this. I went to one of the first meetings that was ever held on the Human Genome Project in Santa Cruz in the spring of 1985 and Bob Sinsheimer had called this meeting because he was thinking about building a center to sequence the human genome. We invited Lee Hood, we invited Wally Gilbert, Dave Botstein, John Sulston, essentially all of the leaders in the sequencing area to consider what could be done. Initially, I think there was a great deal of skepticism. When I received the invitation, I thought this was totally silly. What an absurd idea. You know, we sequenced a million bases but we're talking about three billion bases. Once you started to think about a physical map that that might be feasible, the idea of a sequence stopped being so crazy. It was one of these things which was on the table, was going to take forever. But who knows? Maybe there'd be better technology. We talked about where the technology really was at that time. And I realized that, in fact, the underlying technology, the Red Sanger's techniques and our techniques were capable of sequencing about 100,000 bases a year per person if intensely applied. And when I left the meeting, I became convinced across that time that it was technically feasible to sequence the human genome. And what I saw was basically that the problem was purely an industrial scale problem. Most people in the scientific community said, that's just machine-building. That's not real science. And I don't think that there were many people who had any intimation at all of the kind of revolution that, for instance, the DNA sequencer just by itself, and might all the other instruments that had been developed, that that would have. Because the gearheads understood full well that what they were doing was they were deferring asking a specific narrow biological question because they wanted to ask a vast biological question and they knew that it might take ten years to get the tools to do it. I remember one afternoon when three or four of us were sitting around and kind of the whole vision of how you should do this just came out. I mean, one person said, well, rather than four different lanes with radioactivity, let's use four different fluorescent groups and we can mark each of the four different bases with those fluorescent groups. And another said, why don't we use capillaries to separate the DNA fragments with each fragment being marked by the identity of its terminal base and why don't we have a laser system at the end that can read out the colors as they migrate by. In that one afternoon, we kind of laid out a lot of the different ideas and what was really marvelous about the DNA sequencer is it required the integration of chemistry, of biology, of engineering, and of computer science. The biological community was split about it, I think, and there were those who were really enthused and saw that this could move biology into a new era and there were those who didn't want to go into a new era like biology the way it was and were very much opposed to the idea of big science entering biology. The biology community in the United States could not expect to determine whether or not the nation proceeded with a human genome project. The reason was that the Department of Energy had gained the support for the project of a very powerful U.S. Senator, Pete Domenici of New Mexico. I have two giant great national laboratories in New Mexico. So even in 83, 84, 85 timeframe, I was used to having presentations made on big science projects. One of the scientists from Los Alamos, Dr. Charles DeLisi, he came to my office as a DOE person telling me about a great opportunity. It didn't take me very long to just get committed to the idea hook, line, and sinker. Quite frankly, I thought the scientific community was going to fall solidly if NIH didn't do it. The leaders in the community would have, at that point, were very deeply committed to seeing this happen and they would have fallen solidly behind DOE if NIH decided to bow out. When I heard that, my reaction was not on my watch. I wasn't, you know, opposed to DOE doing what it wanted to do, but from my point of view, this was almost some of the patrimony of NIH. We had had a huge investment in medical genetics, starting in the 50s, animal genetics, human genetics, and it had been moving forward. Every institute was doing something in medical genetics. Lo and behold, the NIH went to Lawton Childs, who was the chairman of an appropriation subcommittee that funded the National Institutes of Health. And instead of arguing, you will note that from the beginning, it was a funding program for DOE and NIH. So the great compromise was, don't try to take it all, DOE. Let's go at it as partners. We got together, and without authorizing legislation, kind of a great feat, it was appropriated. The critics charged that this would amount to a $3 billion crash program that would do nothing more than produce tedious, routinized, and intellectually unrewarding work, and that would, perhaps more important, deprive other parts of biology of necessary funding. What really did turn the tide was there was a National Academy committee set up to interrogate the pros and cons of the Human Genome Project headed by Bruce Alberts. He was completely uncommitted on the question of whether sequencing was a good idea or not. So he was truly neutral. So he was credible to all the parties. So he was the perfect choice. Once you realize that the project was a principle feasible, technologically feasible, and that the ultimate benefits would be very great, then the question becomes a purely practical one. Do we want to spend this amount of money? What is it really going to cost? What's the most often way of doing that? I think what, at the end of the day, persuaded everyone on the committee, including the most skeptical, is that this information was going to transform biology. It was going to free biologists from doing what was at the time extraordinarily costly and labor-intensive work, which is to sequence genes one by one by one, done with really primitive technology, done in the hands of amateurs, which is what a graduate student is, and that to imagine doing this for another 100 years just became inconceivable. Most of the objections were dealt with in the American way by a sensible compromise. It's one of the few examples that I know of where science policy was made by a bunch of middle-aged folks in Washington and actually came out with the right answer. It was good. In 1988, NIH created an office of genome research and announced that James Watson, who was Mr. DNA, would be the head of the venture. This decision amounted de facto to a commitment that NIH would take the lead on the biological side of the genome project. If one looks at, I think, the reason why I'm so excited by really finding out what our DNA messages are. I think it's really two reasons. One, just a very practical one. I think if we find out these messages, we will understand at a very deep level some diseases now which effectively totally baffle us and sometimes almost destroy us. The other reason is, you know, as a scientist, DNA is really the message of life. Watson brought instant credibility. He was the best-known biologist, probably the best-known scientist in the world. For him to walk into a congressman's office and say, we need to start this enterprise because it's going to change everything and it will ultimately benefit human health, he got instant ability to be heard. Never met anybody quite like him. I would say we'd attribute to him and Lawton Childs broadening the base beyond the Department of Energy in a substantial way. As we get these genetic messages, there will be ethical considerations that will come up. And who should know about our genetic imperfections? Should they be open knowledge? Looking at the ethical, legal, social, psychological, economic implications of the human genome was pretty extraordinary because that was quite, quite out of character with anything that the NIH had ever done. I think from the very start, NIH should initiate discussions so that as this knowledge is accumulated, the public is prepared to deal with it. Before the Genome Project, there had been several efforts mounted by the federal government to focus on ethical issues in medicine in particular. And this one was really aimed at basic science and I thought it was about time. There were a lot of critics and the critics said, no, no, no, you can't do this and you're just going to derail the science and it's going to be like a cylinder and there's going to be moratorium and all these people are going to be nacing and talking about problems and it's going to be just hopeless. It's going to be a morass and there are a lot of people who are lobbying him not to do it. From the very beginning, there were some very good senators who began to get worried about the potential for using this impropitiously, things we wouldn't want to do that should be prohibited. Senator Mark Hatfield got involved. My recollection is that there was a set aside that a portion of this money would be used for ethics. There had been discrimination earlier. There were issues of privacy, keeping information private from third parties. So it shouldn't come as a surprise that working with the sciences, we knew it then and we're all just getting started, that the first five-year plan of LC actually focused on some of those issues and lurking in the background was always the question of whether genetics and medicine was going to be different than other parts of medicine. It was a brilliant decision because with the genome we were going to open up a whole Pandora's box of ethical issues. Anyone who had thought about it for longer than 30 seconds knew that this was going to happen and if we were not preparing the community, the larger community for some of these issues, they were going to come and bite us. So in the sense that what Jim was doing is laying the groundwork for community deliberations about profoundly important issues. To date the LC program hasn't interfered with the practice of genomic science, but it has drawn major attention to a whole host of issues raised by the practice of genomic science. Questions, for example, of insurance employment and medical care. At the same time, the LC program has also heightened sensitivity among commentators and public officials to the importance of using human genetic information in ways that maintain privacy and avoid discrimination. The International Genome Sequencing Consortium, the 16 centers in six countries had really learned how to do this awfully well. We're cranking out 1,000 base pairs every second, seven days a week, 24 hours a day. It was roaring into the databases and you could see the trajectory and you could see that we would get a 90% point sometime around June. We are here to celebrate the completion of the first survey of the entire human genome. Without a doubt, this is the most important, most wondrous map ever produced by humankind. It's as if you had knowledge and before you didn't. It is the information that takes a single cell and turns it into a fully formed, incredibly elaborate organism. Us, it's all in there in those three billion letters, the instructions to do that. The Human Genome Project has already paid enormous dividends across the whole domain of biology and medicine. It's revealed, for example, that we have only 30 to 40,000 genes, about half of earlier estimates, and not necessarily a lot more than some lower organisms. It's emphatically demonstrated the necessity of international collaboration in such a project and also the necessity equally of keeping the data that comes in freely and publicly available. I didn't think that in the early stages that I would really be around when they announced the mapping and then the sequencing, particularly the sequencing. I thought that would be too far off, and now we're going to get even that part done. What I was told, mapping is one thing, sequencing is the ultimate. When we get there, then it's going to be up to scientists to figure out how to use it.