 Well, good afternoon, everyone. I'm Eric Green, director of the National Human Genome Research Institute, and I want to welcome you to a continuation of our series on the quarter century after the Human Genome Project's launch. Thank you for joining us this afternoon, especially on such a lovely day. We're tempted to almost have this outside, but that wasn't practical. But it's the kind of day we probably would want to have a talk outside. As you can see from this schedule, we're now in the second half of this six-part series. And we guarantee you will continue the high quality and highly informative talks that you heard in the first half of this series. But we are certainly pleased today to have Bob Cook-Degan from Duke University join us. And I want to tell you a few things about Bob to really set up his talk. In terms of biographical details, he got his BA from Harvard University in 1975, and then an MD from the University of Colorado in 1979. But what's far more relevant for this series has been his history with the Human Genome Project and with our Institute, the National Human Genome Research Institute in particular, which really dates back to really the beginning of both the Institute and of the project. For example, from 1986 until 1988, Bob was an instrumental part of the effort at the Office of Technology Assessment to inform Congress of the importance of the future Human Genome Project and also to provide expert guidance as to who should run it, how it should be funded, and how it should be managed. So by 1989, Bob was brought into the newly formed National Center for Human Genome Research at NIH as an outside expert consultant to help guide the Human Genome Project basically from infancy until about adolescence or so. At the same time, he's also served on our Ethical Legal and Social Implications, or LC Working Group, until about 1991. And then following that, he has served on numerous NIH grant review panels. And he also served on the Secretary's Advisory Committee on Genetics, Health, and Society. And starting in about 2004, Bob was the principal investigator on one of our Institute's funded Centers of Excellence in LC Research. And his grant was entitled the Duke Center for the Study of Public Genomics. Now continuing in that kind of extramural research mode, he's currently a co-PI along with Dr. Amy McGuire of Baylor College of Medicine on another one of our LC grants, which is currently entitled Building the Medical Information Commons Participant Engagement and Policy. Bob is currently a member of the Duke University Sanford School of Public Policy with secondary appointments in internal medicine and biology. And he was the founding director for Genome Ethics Law and Policy in Duke University's Institute for Genome Sciences and Policy from about 2002 until about 2012. The other thing that has brought Bob into recognition within the field, and one of the reasons we wanted to invite him here today to speak in this series, is that he was the author of the book, The Gene Wars, Science, Politics, and the Human Genome. And then meanwhile, in terms of his academic contributions, he's co-authored on over 250 papers. Bob's area of expertise includes genomics and intellectual property, history of genomics, which he'll share with us today, global health science and health policy and health research policy. And his current research focus is on policy implication of genomics, bioweatics, intellectual property and innovation. And so it's wonderful to have Bob here today, and he's going to give us his perspectives about the origin of the human genome project, which as he points out has a political history. So with that, I'll turn the podium over to Bob Cooke-Deegan. Thanks, Bob. Thank you, Eric, and it's an incredible honor to be here. And I had no idea that Eric actually, one more thing that I have to put on the list that Eric knows more about than me is me. After that long introduction, thank you. And I've put to Arizona State University on here, that it's a little premature probably, but I'm planning on making a transition this summer to a new school for the future of innovation in society at Arizona State. And I realized as I was putting these slides together and this talk together, I have actually never given a talk on the history of the human genome project. I wrote a book about it, and I've written lots of articles, but I've actually never given a talk on the history of the human genome project. And so let me tell you what I'm going to do. I'm going to give you a little story of the genesis of what became the human genome project, and then has morphed into a whole field of genomics and its translation into clinical practice and other domains. So I'm going to give you kind of an early history that's real history. And then I'm going to focus a little bit on some features that it didn't look like the other speakers in the series would dwell as much on. So I'm going to talk in specific about the origins of the Ethical Legal and Social Implications Program within what became the National Institute for Human Genome Research, and is now part of NHGRI. And then I'll drill down just a little bit since I lived and breathed patents and genomics for a certain period of my life that's now just coming to an end, and I will be glad to exit that land. But I'll give you a little bit of an example of how some of the research that is done in the social and behavioral and legal areas is relevant to what's going on in the world of genomics. So with that, OK, got the one that works. So the story, so I'm going to tell two histories and just to lay it out explicitly. One is a kind of a technical history and where did the genome project come from in terms of why did it happen, when it happened, and the way that it happened in a technical sense. And then I'm going to tell another history, which is about a way of doing science because there were wars over both aspects of the human genome project, about whether it should get funding at all and whether it should proceed, and also about the style with which it would be pursued if it were to become a reality. So I want to take you back to, so the human genome project officially started in 1990. But the ideas that took root as an actual human genome project all occurred at three different places in 1985. Why 1985? Well, what was happening in 1985, of course, is the idea for creating a map of the human genome that would allow us, without knowing any of the functional characteristics of a protein or the underlying biology, be able to locate where a mutation was originating in the genome by studying a pedigree. And then using a tool, a map, where you could identify which piece of which chromosome came from mom and which part came from dad for each chromosome, the so-called genetic linkage map. The technology for doing that was evolving very rapidly. And the idea for doing that, of course, was the famous Botstein paper of 1980. It was a kind of an idea that probably should have been obvious before, but it wasn't. And the idea of having a human genetic linkage map made it a tool for when you're presented with a family that's got something really bad happening in it and it looks like the inheritance of Mendel's peas, maybe we could find the chromosomal location of the gene that is underlying this thing that's going wrong in that family. And if you have that tool, then you can actually try to find the DNA that explains the variation that you're detecting in the phenotype. So genetic linkage mapping was happening. And also, within certain model organisms, a style of doing research was taking root, particularly in the yeast and the nematode, where they started with genetics, started with DNA, and moved out from DNA as opposed to the traditional way of doing biology, which really focused usually on cells and proteins and moved in the direction of genetics. And finally, there was another movement that was happening which was handling larger and larger pieces of DNA. So cloning them, characterizing them, separating them on gels of various sorts and changing electrical currents so you could separate these very large strands of unwieldy snake-like DNA going through a complicated matrix. So the techniques for beginning to do that kind of work are what Eric was doing when he was a postdoc at WashU. All that stuff was happening in the 1980s. And we were riding hard on the heels of two miraculous discoveries in the mid to late 1970s. And of course, the most important technology for DNA sequencing was the sequencing method itself at the two Cambridges, Alan Maxim and Walter Gilbert at the Harvard in the Cambridge, US, and Sanger and Alan Coulson and the team at the University of Cambridge and the Medical Research Council labs there. So these were truly, I mean, I remember going through a talk in 1975 when Fred Sanger actually took this completely unthinkable thought that you could actually determine the sequence of DNA of an organism by using a technical mean that you could actually do in a lab. I remember my jaw just completely falling to the ground thinking that you could do DNA sequencing. That's 1975. And now, of course, we can do millions in a millisecond. Finally, so this miraculous technology is discovered independently two ways of doing DNA sequencing in the period 1975 to 1977. And then the move to turn that into something that could be done by any lab anywhere was going to depend on instrumentation. And that process was only beginning to gather steam in the mid 1980s. So the first paper, the first automated DNA sequencing paper that gave rise to the machine that undergirded the human genome project, the four fluorescent dye method that was being worked on at Caltech, that paper only came out in 1986. There were things going on in the early 1980s in Japan and in other pockets of the United States. But none of them really amounted to anything that could really be automated on scale and turned into an instrument that any lab could do DNA sequencing with. So all this stuff was just beginning to happen in the 1980s. But something that sometimes gets left out is there are two other fields that were just as important to genomics as managing and studying DNA. And that is the digital technologies and the mathematical methods and approaches that are needed to make sense of the data that we're going to be generated by these new ways of doing DNA sequencing. And the idea of for storing the information in central databases, which is immediately obvious to all of us now, the GenBank EMBL data DNA database of Japan, Troika, that only really began to take root, believe it or not, in the early 1980s. So the GenBank contract, Elka Jordan, who later became the deputy director, was the staff person who pulled together the contract for the original GenBank contract to Los Alamos. And that was awarded in June of 1982. The formation of GenBank is incredibly important because it meant there was a central repository for the information that would be created out of the flow of data that would be coming from labs all over the world. And it wasn't just creating a database. It was also creating a series of databases. And the way that we fund science in most parts of the world is we give them to national science agencies that fund work primarily in that country, with a few exceptions at the margin. But most permanent resources are funded at the national level. And yet you have to create a global resource out of it. So what happened in the case of sequence databases is by 1984, we had an agreement that the DNA databases in Europe, originally in Heidelberg, and then eventually in Cambridge. And GenBank in the United States, which was originally a Los Alamos, and then in the 1990s moves to here at the National Center for Biotechnology Information. And then the DNA database of Japan, all of them agreed to share their data among themselves and do the work that it takes to allow data formats to be compatible and all that. There's a lot of work and it costs money to do that kind of exchange of information. That began to happen by the mid 1980s before the debate about whether there should be a human genome project actually took root. But it's a really, really significant thing. And then think about it. You've got all these data coming out, but how do you put sequences together in the computer? Believe it or not, the methods for doing that were cutting edge math and people had to write papers about that too. And those papers began to come out. The Smith-Waterman algorithm was published in 1981, the BLAST algorithm that everybody uses to compare sequences comes out in 1990. And there are many, many, many other landmarks that I could put on this lineage of bioinformatics, computing, and databases. And then finally, if you think about it, you've got a global project that's gonna draw on information from all over the world. How are you gonna move the data around? If it weren't for the networking technologies that became mature during the 1980s and into the 1990s, culminating in the World Wide Web starting in 1994, all of the work that was being done in the labs would have been much, much, much less productive and it would have been much, much harder to pull all that information into something coherent like a human reference sequence. So that's just setting the backdrop. We've got computing technologies, we've got DNA sequencing technologies, and we've got mapping going on. And all these things are beginning to converge. And lo and behold, this is what happens over and over against science, is multiple ideas hitting the same brains at the same time and people independently discovering the same phenomenon. This is a political phenomenon. The political phenomenon is let's do this on a big scale and let's do a reference DNA sequence of the human genome. That's the core idea that took place in three different brains during this, Anna's Mirabilis of 1985. And there are three completely different historical trends behind the conception in each of these three instances. Bob Sinsheimer was the chancellor of the University of Santa Cruz at the time this idea came around in 1984. And Santa Cruz is really good at cosmology and telescopes and stuff like that. And they've gotten a grant from the foundation that comes from the importer of BMW machines, BMW cars in the United States. And they had a grant to build a telescope that one of the telescopes is actually, actually was eventually built on top of the mountains in Hawaii. But they only had $36 million from this foundation and it was gonna cost $70 million to build the telescope. So they decided to go out and see if they could get other people to contribute but they had already decided to name the telescope after this foundation. And what actually happened is the Keck Foundation funded this telescope, which is now called the, guess what, Keck Telescope. But that meant they had this $36 million check from another foundation that had been intended to build that telescope. And so they had to send the check back. And if you're the chancellor of the university and you have to give a check back for $36 million, it's a painful experience. So Bob Sinsheimer is faced with, well, what could we do with this money? And maybe we could talk the donors into doing something really spectacularly useful. Let's create an institute to create a reference genome for the human genome. Just the same way that when I was doing my laboratory work as a molecular biologist, we did the sequence of Phi X-174, a virus. We're just gonna scale it up and we'll do that work here at University of Salt, California, Santa Cruz. So he gave the check back, the family falls apart, they don't converge on it. They never actually got the money back at University of California, Santa Cruz. But the idea was there and he decided to hold a meeting of some of the poobahs of this emergent field that eventually became known as genomics, people that were handling all this DNA information. And that meeting took place in May of 1985 at the University of California, Santa Cruz. And he started writing letters. So there's a letter in the file to the director of the NIH saying, wouldn't you wanna do an institute for sequencing the human genome? We'd be happy to build that here at the University of California, Santa Cruz. That didn't go over too well. And the answer was, guess what? You guys work at NIH, what's the answer? Well, you could apply for a grant. And that wasn't gonna go anywhere. So that was the story of the last check. Go down the coast a bit in California to the San Diego, La Jolla area and Renato Delbeco at the time was the president of the Salk Institute. Very creative Italian American scientist who had turned his turrets towards studying cancer and thought, wouldn't it be marvelous if we had a genomic sequence, a reference against which we can compare the mutations that arise in the process of developing cancer. So for Delbeco, the idea of doing a human reference sequence was as a tool to understand variation that's associated with cancer. And he published an article based on that. He gave some lectures over Columbus Day at the Italian Embassy in Washington to spread his idea. And then he published an article that came out in Science Magazine in March of 1986. But that route, that idea really didn't take root either. And it's like many ideas in science. You have multiple independent discoveries but some of them go someplace and some of them don't. And the top two here, Cinchimer and Delbeco actually didn't really lead to anything except discussion. The final instance of the idea of a human genome was Charles DeLisi. Now Charles had been here at the National Cancer Institute, trained as a biologist, and then he'd spent some time at Los Alamos learning, well, not learning. He had very strong mathematical backgrounds. He became the dean of an engineering school. So he's one of these people that was doing biology and math at the same time, kind of a rare creature in those days. But he was really interested in both fields and he had become the head of the program within the Department of Energy that did some biology. And in fact, in the post-war period, this was the main source of genetics for the whole country until NIH got bigger. And genetics became part of the mainstream of biomedical research. But the Department of Energy had a genetics program that got all the way back to the Manhattan Project because even as the Manhattan Project was happening, people had discovered that radiation does bad thing to human bodies. So, you know, Madam Curie dies of cancer, Renkin. All the pioneers of this field have discovered by using their own bodies that radiation is not good for you in high doses. Moreover, when the U.S. dropped the bombs over Nagasaki and Hiroshima, in the post-war period, it became obvious that we should try to understand what that meant to the human beings who were exposed to this radiation. There was a whole research program under the Atomic Energy Commission to study what was going on there. And James Weingarten, who was the president, who was the chief of NIH, the director of NIH, at the time the Human Genome Project finally came to full fruition, had been participant in the process of studying radiation effects. So, Charles DeLisi has the idea for having a reference sequence of the human genome by reading a report authored at the place where I used to work, the Office of Technology Assessment, that had been asked by Congress to say, do we have the technical capacity to detect variations, inherited variations in the human genome? Thinking very specifically about the people who had been exposed in Japan and whether you could detect whether the mutation rate was actually higher in their descendants, then it would have been if their parents had not been exposed to the radiation. So, it was a technical question and there was a report written about it and Charles DeLisi is reading this draft of this report in October of 1985 and says, you know what, let's solve this problem, let's just do a reference genome and then we would do, it's kind of the same idea as DeBeco had. Once you have a reference sequence, you can compare variations against it and use it as a tool for understanding the phenomenon you're interested in. But he also had this incredibly strong background in what would now be called bioinformatics and he had worked with the theoretical physics group at Los Alamos and he knew those guys. And there was a whole lineage of people, Stanislaus Ulaum, Walter Goad, mathematicians, Michael Waterman, people who had spent time in the national labs doing high tech, using big computers, doing complicated calculations to understand natural phenomena and those folks were beginning to get really, really interested in applying that new technology to sequence information because there's this really natural alliance of thinking about a binary code in digital bits and the quaternary code of the A's, G's, T's and C's of DNA and moreover, there's this database that's now housed at Los Alamos National Lab which is the place where most of that information is finding its rest, its final repository. So Delisi was well positioned and most importantly, he had a budget. So he had a budget and he asked permission from the office management budget and all up and down the Department of Energy, could I start spending money? This seemed like a really, really good idea and you guys pay me to have good ideas. Can I please pursue this? And he redirected some money into this program and then he asked for a formal authorization of an ongoing program and that was the core that gave rise to the Human Genome Project and that's where the term began to take its current usage, Human Genome Project. That was a proposal within the Department of Energy to do this thing and the original talk coming out of DOE is we're gonna do it, we're gonna do it within the National Lab system. Little side project, those of you who've read my book know this quote, but so Jim Weingarten is the director of the National Institutes of Health which is about a good 10 times larger than the biology programs of any other federal agency and he got wind of the fact that there was this DOE idea for a Human Genome Project when he was at a cocktail party in London and basically he said, I think what I said back to the person who asked me about the DOE project was that's like the National Bureau of Standards asking to build the B-1 bomber instead of the Pentagon so and that was pretty much emblematic of how most people at NIH and in the core molecular biology community reacted to this idea of a DOE led effort to sequence the Human Genome. So that led to a period and here I'm gonna shift from the technical origins to the political story of the origins of the Human Genome Project because what do you need if you're gonna do a scientific program? So think about what we're doing now with the National Cancer Moonshot Program for example or the Precision Medicine Initiative. Well, you need plans, you need people and you need a budget and a lot of policy is discussed in the framework of creating new line items in budgets so that you have authority to spend money on the things that you're trying to use the money to achieve. So within the Department of Energy, that's an inside game. You ask your bosses within the Department of Energy and then the bosses at the Department of Energy ask the people at the Office of Managed Budget and then they have to get permission from the president and the president puts this into his budget request and then it goes to Congress and Congress does whatever it's gonna do with it but usually what Congress does for most line item budgets is they'll yell about a few that are controversial and then they'll just pass the bundle that's suggested by the agency so that's kinda how it works for the Department of Energy. A lot of work for Charles DeLisi within the OMB framework but it's mainly an executive branch story. NIH, however, has this long history of being the golden child of Congress where and maybe we're back in that era again now a little bit after a 12 year period where NIH has been left out in the wilderness and lost 22% of its buying power since the doubling ended in 2003 but up until that budget doubling period NIH has always had a tradition of getting money from Congress that was not requested by the president. So it's much more dependent on the appropriation subcommittees in the House and the Senate that give money to NIH and new priorities for NIH, new institutes and new big line item budgets and new highly conspicuous centers tend to have congressional action associated with them quite directly. So that was true for the Human Genome Project and the origins of the Human Genome Project. There was some lobbying people like Jim Watson, David Baltimore, met with members of the appropriations committees and stuff like that but the story of getting the budget for the NIH Human Genome Project is actually pretty mundane. There were a bunch of hearings and in those days the hearings would go on for a couple of weeks in the Institute by Institute and in one of them it always starts in the House and the members of the House asked for a budget of what NIH would do if they got more than the president asked for and Jim Weingarten, leaning on the directors of all of the institutes and centers at NIH went through a very formal process of saying if we had $100 million more than they asked for 200 million, 300 million, 400 million, they went up and there were two lump sums for genome mapping and sequencing, wasn't called that yet. It was gene mapping and sequencing but two of those increments were in the first 500,000, 500 million that NIH actually got that year and the way that that happens is Jim Weingarten sent his budget recommendations to the staff at the Appropriations Committee and the staff person, Henry Neal, in the House of Representatives put it on the spreadsheet and that's the story of the origin of the Human Genome Project. It's a very mundane entry in an Excel spreadsheet for that year's budget that's gonna go through the Appropriations Subcommittee. So all this lobbying and all this discussion that was going on in the big grand world, the guy who made the decision about making the entry was completely oblivious to that and he basically was doing what his boss told him to do which is go up to increment number five in the extra money that NIH should get this year. Now, it's not that that outside discussion was completely irrelevant because we had this idea, let's have a reference genome of the human genome. It was dependent on having a map of all the DNA in the human genome. It didn't make any sense unless we already had a genetic linkage map so that we could use as a tool to understand diseases and phenotypes in humans and we had to have enough sequencing capacity to actually do the job and none of those were even remotely close to possible when this idea first landed in 1985. We did not have the technical means to do the Human Genome Project in 1985. Many, many people had faith that yeah, if we start spending money on it, we'll have it by the time we're done but it really was not technically possible. One of the sources of controversy. So there was a very, very active debate and there were two debates going on simultaneously. One is in the great big wide world of politics and members of Congress thinking we love NIH, we really love the idea of the National Labs doing something in biology that will do something useful for the world. This idea of having a reference genome of the human seems like it's really cool and it'll help us solve disease and so at that level there's a lot of support in Congress but it also costs money so you have to go through a debate of compared to other expenditures, is it good? So there's that level of debate but then there's also a quite turbulent and we were nowhere near consensus within the molecular biology community that this was a good idea at all and the debates were twofold. One is can we do it? Does it make sense to say you're gonna do this in 15 years when we don't even have the technologies to do it now? And there's a debate about yeah, sometimes you say yes and sometimes you don't. Moreover, there was also a question about is that the right way to do biology at all? Do we do large scale things like this in biology and there was a kind of a spiritual or sociological debate within molecular biology about whether we wanted to go to the dark side of big science because when you have big science you have big budgets and you have big politics and it is true. So it means that you're gonna have NIH inspected under the microscope by Congress every year on what it's doing in this particular domain. So in the face of that controversy, two things are going on. Number one, there's a lack of consensus that's kind of obvious because people are yelling at each other in Science Magazine and Nature and the New York Times and there's also another problem which is you've got the Department of Energy and the National Institutes of Health, both of which have a legitimate stake in this idea, both of which wanna do something with it and actually both of which wanna run the thing. Now where are the points of convergence of the Department of Energy and NIH? NIH is part of the Department of Health and Human Services, the only point of convergence, there are only two points of convergence in our federal government. One is Congress and the other is the Office of Management and Budget and this is not the sort of program that was gonna be solved at the level of the Office of Management and Budget. So it was largely a question of figuring out the constituencies and getting support from Congress. Now how do you do that? Well, a group of people, mainly Jim Watson, saw that this was an important thing and that they needed a tool to make the argument to lay out a coherent plan and they turned to the thing that was created in the Civil War to give advice to the federal government and that's the National Academy of Sciences and the operational part of the National Academy of Science called the National Research Council. What do people do? They get paid to do reports on matters related to science and technology. They produce a report that says, has findings and recommendations and they produce that as a package that then becomes a tool for doing the policy analysis and making the policy decisions that follow from the recommendations. So the McDonald Foundation wrote a check to the National Academy of Sciences, caused some consternation there because the project had not been approved at the NAS when the check arrived because they moved really fast in the McDonald Foundation. But eventually this project got launched at the National Academy of Sciences to say, should there be a human genome project? That's basically the question that's on the table. And at the same time, within a day, at the Office of Technology Assessment, which is where I worked, we were asked by the committees that had jurisdiction over both DOE and the National Institutes of Health to prepare a report that said, at OTA we don't make recommendations. At OTA we would say, what are the choices that need to be made and what are the facts that are relevant to making those choices? But we weren't supposed to make the choices. That's for our bosses, the members of Congress to make. So in one very short period, these two reports go forward and they are the tools that policy makers are gonna use to make a decision eventually about whether there should be a human genome project. While those projects are going underway and the National Research Council project was really, really important because it had two tasks. One was to reach consensus within the scientific community about whether it made sense at all. And the other was, if it does make sense, let's have a plan for how to do it. What are the components and how do you go about doing this? And the NRC basically had a bunch of really, really smart people on it. And their job was basically to lay out the plan, the scientific and technical plan, and to endorse that. And that's exactly what they did. The OTA was left with a different set of things and basically we looked at tech transfer policy and we looked at all the other questions. But the question that the NRC committee could not answer was who's gonna run it? And we also ducked that question because OTA always ducked questions because we were paid to duck questions. We were not supposed to answer them. We were supposed to help other people answer those questions. So the question was, should NIH or DOE run it? And if you think about that for 20 seconds, you would realize that either answer, NIH should run it or DOE should run it, was going to lead to an internecine battle because you have patrons for both organizations and constituencies who are not gonna be happy having their operations shut down and they're not gonna give their money to the other side. That just doesn't work. So actually the only answer was pretty obvious, which is of course you're both gonna have a program and what we need to do is solve the problem of how are you gonna make sure that it works together? And that was really the problem that was solved and it was solved in the Senate by having a bill that said here's the framework, you guys are gonna work together, that was set in statute. It passed by a vote of 88 to three, as I recall, in the Senate. So very few dissents. And those were probably purely ideological. I'm not gonna pass a bill on anything. And in the House, it goes over to the House and the Energy and Commerce Committee is saying, hey, we've got this bill from the Senate, should we pass it or not? And a science and technology fellow, Leslie Russell, working for John Dingell, who's the Chair of the Energy and Commerce Committee, had really good technical training in genetics and basically said she called up Jim Weingarten here at NIH and called David Gallis at the Department of Energy and said, hey, you know what, we could pass this bill, but wouldn't it be better for you guys if you kind of figured it out for yourselves? So that's kind of what happened, is that NIH and the Department of Energy, the leaders of the two programs basically got together and crafted a joint advisory committee. So you guys know how NIH works, right? You have a council that has the spending authority and you have advisory committees left and right, you have study sections. So you had to have all that for the part of NIH that would do the Human Genome Project and that's eventually what happened with the National Center for Human Genome Research that then became the Institute. And you have the same thing at the Department of Energy, but you need something also, now the two agencies have promised that they're gonna operate together, so you need a layer of things going on that join the Department of Energy and the National Institutes of Health and also things like the Bureau of Standards and NSF and the Department of Defense, all of which have some contributions to make to this. So that's the framework that began to emerge and we finally kind of finished the story of the origins of the Human Genome Project. So it's launched and one of the stories of the launch is again, a decision that was made by the NIH director was Jim Weingarten's decision to appoint Jim Watson as the first head of what was originally the Office of Human Genome Research. That's a kind of a coordinating office and it didn't have spending authority until it became the National Center the following year. Jim was basically the Colossus who stood over this project, but he was also running Cold Spring Harbor Lab and he was spending at most a day a month, a day a week here in Washington, D.C. So the staff who actually kept things going and actually ran the program and crafted it and did all the hard work were here down in Washington and basically imported from the National Institute of General Medical Sciences, all people trained by Ruth Kerstin, an incredibly talented woman who was originally completely opposed to the way that the Human Genome Project was taking shape, didn't think we should do big biology in the way that it was being planned from the top down and basically lost her battle with the Jim Watson faction over control of this project. To her credit, she kind of changed her mind about whether she was kind of glad she lost that battle in retrospect and she said as much publicly several times later. But she had this very able set of staff who came over here and some of them, you guys know them better than I do, Elka Jordan, Mark Geyer, Jane Peterson were among, Betty Graham among the early folks who ran the program. And then the three labs that, the two labs that had been most heavily involved, the California Livermore Lab and the Los Alamos Lab in New Mexico but run by the University of California. They were the key elements in the DOE effort that gave rise then to a joint genome institute that was created in the San Francisco and Walnut Creek in the San Francisco Bay area. So now we have a budget. We have promises of a growth in the budget and we have two programs, one in the Department of Energy and one in the National Institutes of Health. What are they gonna do? Well they're gonna do a genetic linkage map and people like Mark Geyer are responsible for herding the cats that you need to herd using the grant mechanism to get people to achieve a common goal. An incredibly difficult bureaucratic task that they managed to make work. We had to do a physical map. That is take the DNA itself, clone it and put it in a refrigerator so you can sequence it and also use it to study whatever's going on. So that physical mapping and sequencing effort had to go on in parallel. And then in the area of sequencing, the technologies for the four color fluorescent sequencing were still being done in slab gels in those days. These huge gels that took a really long time to mature. It was never gonna be a scalable technology. And the automation of that, a whole technology development program began to take root here in what became the NHGRI. Carol Dahl, Bob Strasberg, Jeff Schloss, Jane Peterson, all folks who took a role in crafting a tech push program within a biological institute. That gave rise to the technologies, almost all of the technologies that are being applied to DNA sequencing together. And finally I've already alluded to the fact that this repository of DNA sequencer information that was originally housed at Los Alamos was moved into the National Center for Biotechnology Information at the National Library of Medicine in the 90s. NCBI was created in the same bill that gave rise to the genome project in 1988. So we go through this establishing the bureaucracy beginning to do the mapping and developing the sequencing technology so that they're scalable. And then in 1996, NIH and DOE and the rest of the world began to shift gears into the sequencing phase. And I'm mentioning this as a special thing partly because it's a technological story and it was the shift to capillary sequencing which was much faster, more reliable, longer reads and simplified both the bioinformatics and increased the throughput of sequencing. So it actually did become possible that if you ran enough of these machines for long enough you could actually come up with a reference genome or the whole genome. But there's another story here that I wanna spend a little bit of time on and this is where we get into the philosophy of how do you do science. In 1996, the first grants have been given out by the Wellcome Trust and mainly by the National Institutes of Health and the Department of Energy to scale up the sequencing using the new technologies that have just become available. And a bunch of the labs that were gonna take the lead on the high throughput sequencing were invited to this meeting that you all have heard of that took place in Bermuda in February. The weather was miserable, why did they pick Bermuda? Not because it's an exotic island in the middle of the ocean, but because it's a British, not an American island and this was gonna be organized by the Wellcome Trust and it needed to be conspicuously neutral. Couldn't be in Europe, couldn't be in the US, couldn't be in Japan. And hotels are cheap in February. So they had miserable weather but they did incredibly important work and the Bermuda principles, we know them now because they came up with the rules for daily sharing of sequence data at the high throughput centers. It was probably the high watermark of the open science movement up until that point. So basically this is everybody pledging to share their information publicly before they'd even had time to think about it as a resource, as part of a public works project to create the human reference sequence at these high throughput centers. But there was a very practical reason for doing the Bermuda rules too because think about it, you gotta sequence the genome, you gotta figure out who's gonna do which part of chromosome one, two, three, et cetera and if people are claiming they can do sequencing at X level of accuracy and speed, you know what? Turns out the scientists don't always tell the truth when they're asked to tell the world what their goals are and how quickly they're gonna achieve them and they had a trust problem they had to solve which is if we're gonna allocate a region of the genome for you to sequence, we need to see the sequence so that we know that you're doing it and we need to know what degree of accuracy. So these rules about open disclosure of the data had two purposes that were completely in alignment. One was a spiritual commitment to open science and the other was trying to make sure that they could actually meet their objectives and the only way to do that was to make it very public and make failure highly conspicuous. So the Bermuda rules had all of these subtle undertones and it turns out that it wasn't a kumbaya moment because these policies actually violated national policies in Japan and Germany because at that point, the idea of the human genome project grew up in an era that I'll talk about in just a minute which is you know what, this science grew up in the era of biotech and it was really obvious that some of this stuff was gonna be really valuable in a commercial sense not just a scientific sense and therefore many governments around the world were thinking oh the hot new science here is genomics, let's put money in that but you know what, if that's gonna be commercially valuable the companies from Japan better have first access to that data or the companies from Germany better have first access to that or the companies from France or the companies in the United States. So it was national policy in several countries to give privileged access to local companies and the Bermuda principles actually completely countermanded that and there was a period of about two years where Francis Collins and Harry Petrinoce and Michael Morgan were sending nasty grams to bureaucrats in other countries to say play by the Bermuda rules or we won't say that you're part of the human genome project and it actually worked but it only worked in that very discreet context. So that's part one of the Bermuda thing. The other thing to notice is in 1998 the game changed. It stopped being a pure public works project and it became a project that was perceived by the outside world and in fact in some reality was a direct competition between a publicly funded human genome project and a privately funded corporate effort to sequence the genome using shotgun methods as opposed to physical map and then do the sequencing based on components of the physical map to construct a global sequence. There was a technical argument about is it better to do the whole genome, blow it apart and put it back together in computers or do you do your sequencing based on the physical map? And on top of that, Solera, the company that became eventually Solera in 1998 announced in May of 1998 and then actually an actual operational company by the end of that year was planning on making its data and it did make its data available only on a subscription basis to corporations that would pay for access to it and actually some places like NCI paid for access to it as a research tool. So there was also an overlay of a competition between the public sector and the private sector and so from 1998 until 2001 when the draft sequences were published in nature and science in one day after the other, we had what I think is accurately described as a genome war for primacy and there was a lot of quote to quote combat in the Washington Post and the New York Times between the leaders of the two respective projects. That was called to a truce long enough to have a press conference in June of 2000 in the White House and at 10 Downing Street, the US and the UK that paid for 91% of the sequence that went into the original reference draft sequence and that truce held for a good week or so and then gave rise to the public genome project basically catching up and populating the database which made the proprietary value of the proprietary sequencing effort much less valuable so within a few years after that Solera deposited its data in GenBank. And then of course beyond the June 2000 and the publications in February 2001 actually the work of turning this first draft sequence into actually usable scientific tool took place chromosome by chromosome and finished depending on where you put the finish line sometime in 2003 or 2004. So just to summarize that's a lot of complicated history but what do we have? Well we have a human genome project that for the most part was modeled on model organisms and the model organisms in particular were nematode and yeast. And why do I use those two examples? Those were the open science organizations that had organized themselves around having certain groups get lots of money to do things like build common resources but then share it with a very broad network. There's a hub that got a lot of money to do stuff that was expensive in high tech whiz bang and created information and materials that would then be shared with a network through spokes out to a group of laboratories that were much smaller and organized according to the way we usually do biology. That was the open science model. Just to flag it and make it really explicit that's not how the human genome project would have evolved had it been run by the human genetics community. Cause the model in human genetics was get your pedigree get your phenotype, get your family then do your find your gene and then sit on your family and mine it for your whole scientific career and keep that under your control. It was a community that was pretty accustomed to not sharing data until the point of publication and sometimes even after publication. Data could still be sticky. So here's a particular way of doing science a sociology of science that came to prevail and the vectors of that were Bob Waterston and John Sulston in the UK doing the nematode project and then the whole cluster of people doing yeast. Maynard Olson was one of the key advisors you heard from him a couple months ago but there was an ideological and sociological shift within the human genome project and I think the project was vastly, vastly improved by modeling it on nematode compared to the other models that were out there and available. I'll just spend a moment on one other aspect of the history of the genome project because if you think about it idea of conceptions in 1985 what else is going on in the world in 1980s related to biology? Well, the word biotechnology in the sense that we mean it today as an industrial sector was first coined in 1980. The term existed before then but it didn't mean what it does now and the Cohen-Boyer patents are granted starting in December of 1980. The Bi-Dole Act is passed in December of 1980 and this sets the stage for saying you know what? You can patent this stuff because it's really valuable and it's gonna be commercially relevant and universities are gonna be part of a cluster of institutions that are really important and universities are gonna be part of the engine of economic growth and biotechnology is gonna be one of the places where that growth is faster than in other sectors of the economy. So the human genome project grows up in an era where this debate about commercial biotechnology is completely lively and we do have the EST patent battles that are directly connected to the genome project. The intramural project here that Craig Venter was running before he went to the private sector. The first patent applications on express sequence tags, little pieces of express sequences out of CDNAs, those patents were filed by the National Institutes of Health in 1991 and a debate that went on until 1994 when Harold Varmas decided no, no, no, we're just gonna stop this process, we're not actually gonna try to get those patents. And then, of course, discovering of the CF gene, discovering of Alzheimer's genes and probably the most conspicuous battle of all was the race to the BRCA1 in two genes that took place, the starting gun starts in October of 1990 with the discovery of genetic linkage to chromosome 17 for BRCA1 and then the discovery of the actual sequences in 1994 and then 1994 is when BRCA2 is mapped and then it is sequenced by the end of 1995. So this period when the human genome project is taking root is also a period of ferment within biotech and commercial biotech and a lot of really, really vigorous debate about what to do about gene patents. And a lot of private firms beginning to enter the space and even at the very beginning of the human genome project, companies were beginning to get formed, these two insight and human genome sciences were starting from CDNA sequencing and moving towards rotating their business plans around sequencing CDNAs and staking patent claims on the genes that would be fished out by using the CDNA sequences. And of course, this is a picture of the attendance of the first of the Bermuda meetings and the whiteboard on the right is the actual, this is John Sulston's writing. This is the statement of the first draft of the Bermuda Principles about data sharing at the end of every day and you'll see something called policy at the very bottom. And I'm at NIH so it's okay to say basically the funding agencies are the people who are gonna have to enforce this. So I'm gonna spend just a few minutes about another part of the origins of the human genome project because it's an experiment that was a grand social experiment that has not been often replicated. And it's something that happened on this campus at in this building but not this particular lecture hall but when Jim Watson was first introduced in 1988 as the director of what would become the Office of Human Genome Research, he announced, he gives his talk and he's introduced by Weingarten and the other people that are at the podium. And then there's a Q and A session at the end of his talk and he was asked a question by a reporter, what are you gonna do about all these concerns about genetic testing and patenting and all the stuff that's going on that's related to your human genome project? What are you gonna do about those issues that relate to the social and legal and ethical issues that are connected to the genome project? And Jim basically announced that he would spend some of the research budget on what became known as the Ethical, Legal and Social Implications Research Program that was built into the National Center for Human Genome Research and actually was, there's a congressional mandate that was inserted in the second iteration of the NIH Authorization Bill that passed in 1993 that said 5% of the budget will be devoted to studying the legal and social implications of what's coming out of the human genome project, both the way the science is conducted and the way it might be applied in the real world. So why in the world is NIH getting into the business of supporting that kind of research? Well, I think there are a whole bunch of reasons and if you think about it, one was that everybody was gonna ask questions about it because this is the field of human genetics, it's obviously related to human genetics and human genetics had this really spotty history of being tightly associated with the eugenics movement and statutes against interracial marriage and involuntary sterilization statutes, all sorts of stuff that morphed into racial hygiene and gave rise and was tightly associated with the Holocaust in Germany and in the post-war period, it was a toxic combustible mix and in the 1980s, this is really, really important, scholars began to examine that. So the New Yorker ran a four-part series that became the book in the name of eugenics written by a historian, Dan Kevles, a historian of science who started in physics but then moved into looking at eugenics. Those papers were coming out in 1984, 1985, just as the human genome project is taking root. Moreover, we have all these genes that get discovered and the debate about what are we gonna do with genetic tests for hunting disease, for breast cancer, for Alzheimer's disease, for cystic fibrosis, for neurofibromatosis. The technical means for actually doing genetic testing that we've been talking about for years actually became a technical reality and therefore the issues became much more urgent to address and this program, because it was associated with the DNA analysis, became the place that the responsibility for conducting that kind of research came to rest. So there was an intellectual reason to do it but there was also a sense that unless you had a program and you could say, yeah, we're gonna do something about that and this is what we're gonna do. We're gonna have a research program and we're gonna think about these issues. You were gonna get asked that question. So in a way, there is a truth to the fact that the ELSI program is created in part to be a shield for the science because we wanna go on with the science and we don't want all these social issues to get in the way and block Congress from being interested in what we're doing but at the same time, they're actually really legitimate things and it's a new move saying, you know what? Law, humanities and the social sciences are actually relevant to translating the science that we do at NIH into things that matter in the real world. And you know what? It would be a good idea to study that and maybe even do something about it. So that was the origin of the ELSI program and it took root, Jim basically made the announcement and then they hired Eric Youngst, who was trained at Georgetown as a PhD biathesis, had gone into academia, came back to NIH for a while and then went back to academia. Again, he's now at the University of North Carolina. And it created a research program and I wanna give you just one other input to this was one way you would know you need to have a program like this is if you read both the NRC and the OTA reports, these issues infuse the whole analysis and any science administrator reading those reports would have said, oh, we better do something about it. And if you had any doubts about that, all you would have to do is go to the hearings that were held about the human genome project as it was taking flight and getting off the runway and listen to the likes of then Senator Al Gore and John Kerry go after the Department of Energy when they said, oh, I'm not sure we're gonna have a program like that and getting beaten about the head until they agreed to have an LC program as part of their program at the same time in the Department of Energy. Moreover, every national program that grew up in this era also developed an LC program, even in Japan. They weren't always big, but they were always there. And the LC program, one other landmark just to give credit to Elizabeth Thompson who is no longer with us. But one of her, part of her legacy is the centers that emerged. So basically, LC research got big enough that it made sense to do it the same way we do other domains of research, which is get clusters of people to work together in big centers and train people so that they aren't just doing it at the R01 level. One thing to observe about it, though, is that this experiment has actually not gotten replicated in other parts of the National Institutes of Health. Nor really very often in other parts of the federal government. The Nanotech Initiative had a bit of an LC component to it. And every once in a while, you'll see an ethical and legal research program tied to a technical initiative, but it has not become the mainstream and it hasn't become the default in thinking about building a new research program. And I'm gonna finish by just asking the question. So if you've got an LC research program, how do we know that this is a good expenditure of funds? Because when we're using federal dollars, we need to be able to make a pretty good argument for this is a good expenditure of these dollars compared to the other things that we could be using the taxpayers' dollars to fund. I think we can cast aside the PR shield thing, the thing that you need this in order to be able to do the science, because I don't think that's a robust base for a scientific program or a research program of any sort. And I also think political support for that is gonna be extremely fragile and vacuous, frankly. But does it make sense to have a body of research that is relevant to creating expertise that helps people make better policy decisions about the things that are gonna be growing out of science? And I think you can tell what my answer is going to be is a yes, but I'm gonna give that yes in what I hope is a somewhat textured way. It's not just the nature of the research, it's the fact that we're talking about an ecosystem in which there are very, very many moving components. And if you think about a car or something like that, if you think about we want to build a car, we wanna do something useful, we've created a useful technology, and we know it's useful because we use them every day, and they're really important in our lives. You then have to come out and well, how are we gonna build the components of the car? So you have a carburetor, you have the tires, you have the transmission, you have the pistons, you have all sorts of things, and you actually have to have all of those components in order to have an operational car. The first cars didn't have everything that we now have in a car, but they had enough different components that the car began to work, and then we kept adding bells and whistles, and today's cars are really, really complicated and have many, many components, each one of which is absolutely essential. And I would argue that the LC program is in a way the equivalent of having a functional element in a really complex machine, the machine being the way of creating the science that we need to make the new technologies and make them meaningful in our lives. And I like to think that maybe the LC program is kind of like the windshield. It's the thing where you need to have a clear view of what's gonna be coming at you. And original cars didn't have that, and lots of bad things happened when you didn't have a windshield, and it was discovered as being really useful to keep the flies from hitting your eye at a crucial moment where you're about to drive off the road or hit a rainstorm. So I would make an argument that it actually made sense and to those of you from other parts of the National Institutes of Health, I would argue that in fact what you guys do in your domains of science might also benefit from thinking systematically and in a concerted fashion about how to build such a similar program. Thank you. Thank you. Thanks, Bob. Please, people come to microphones and we're assuming we have time for discussion. So why is it that other parts of NIH wanna drive fast without windshields? I mean, why is it that there hasn't been more common uptake of LC elements in other parts of NIH, as you point out? I think there are two explanations. One explanation is a feature of our field that is inherent in what it is you're doing if what you're doing is observing people that are doing science in the lab or in the doing practicing medicine in the clinic, and what you're doing is studying what they do and what you're gonna write your papers about is if you're doing a good job, you're gonna say what's gonna go wrong and how's it gonna go wrong? Cause that's why you're being paid is to identify problems that are going to arise. What that means is you're gonna be a finger wagging bioethicist who isn't doing what they're doing and you're gonna be saying don't do that because you're gonna screw this up or that up and your job is going to be explaining the problem and actually that's not all that fun to think about. So I think bioethics has, and this is what we do. If you're in the Department of Defense and you're thinking about what do we do in the wake of an atomic bomb? What you do is you construct a worst case scenario and you do your analytical thinking based on the worst case scenario. The problem with that is if that's the only part of the world that you're thinking of you actually don't think about the benefits that are coming from the other technologies that are gonna arise out of your research program. So there's a bias there and there's a finger wagging aspect to bioethics that I think some scientists don't love it too. They don't really love the idea of spending their money on that function. And then there's a cultural issue. It's a different domain. It's a different set of disciplines and it is not the mainstream. And NIH is incredibly good at funding high quality science over time. But this is not defined really as science. There's a debate about should we be funding the social sciences that goes all the way back to World War II. Vannevar Bush, who wrote Science The End This Frontier thought spending money on social science was a terrible idea. And yet the Democrats in the day, the Truman's, the other factions, the those days Democrats, believed that social science should be inherently woven in to science programs and we've had this debate going on and off. But I think it's partly at a place like NIH, look what most people do is they fund science. And this is kind of at the outer edge of that kind of science that's mainstream at this institution. But you made the point that then Senator Gore, then Senator Kerry pushed back at the DOE. So why, I mean, why are other members of Congress, if they're seeing some of this and it has to be in other scientific domains, why are they not pushing back at us the way they pushed back at the DOE? So if they were the ones who were making most of the science policy decisions, there probably would be more of these programs around. So when you get up to the level of nanotech, what's common between the genome project and the nanotech? It involves multiple agencies and it got up very high in the reaches of the federal government where most of the architecture of the new program got emerged. Most science programs happen down in the agencies and the agencies craft their plans according to what they're trying to do and your mission is to do the science, not to think about it. But they are due of interactions with the members of Congress that I would take. You have interactions but think about it. When you wake up in the morning and you're Senator Gore or Senator Kerry, you're confronted with the issues of solving the problems of the world about your blessed, believe me. So they have to be thinking about all those issues. So when those points, when those issues converge in your brain, you have to think about that stuff. So you're gonna appreciate the value of having economists thinking about issues and historians informing your decisions in a way that the scientists who are basically thinking about doing their stuff in the lab that day are not gonna be thinking at that level. So I think that's part of the explanation for it. Here we have a question here. Hi, Dr. Cooke-Degan, John Latempio. I'm a program analyst at NHGRI and I think that we talk a lot about in our office is the generalizability of the work that we do. And I think that something that is interesting from your very long view of the history of this entire field is that it's almost like NHGRI or all of the names of our center office, now institute, office center, now institute, almost ran a giant social experiment on how you coordinate disparate groups who didn't like to play nice together before. Is it, or do you think it falls to the job of policymakers and scholars of policy to look at HGP and other projects like it to see how they can generalize it to other large scale projects that the government may be interested in? Or is it our job as genomers who have watched this happen to go out and act as champions to it? Well, so I think that's a false dichotomy. I think you need to do both. But the other thing that I will observe is really hard to generalize from an N01. And that's kind of, to a first approximation, that's what we've got. So I actually, I'm sure that we made lots of mistakes in crafting the ELSI program. And I say we, because I'm not casting aspersions on Eric or Elizabeth or anything, but. The other Eric, not this one. Yeah, the other Eric. Eric Young, sorry. You're gonna make mistakes, but I think we actually don't have the capacity for anything because we don't have much diversity out there. And I actually think complicated, wicked problems like these, we don't have analytical solutions. Usually we stumble towards improvement by having all sorts of trying things out and discovering what breaks and what doesn't break. And we don't really have very many instances of this out there to do some comparison. So I would love for this virus to spread a little wider. One other thing that's really not good about it is that genetics has borne almost the whole weight of thinking about all the problems that come out of all forms of biomedical technologies. So, and sometimes that makes sense, but think about it. The debate that's going on right now about the incredibly tawdry state of forensic science in the United States. You know, people go to jail and get killed by the government because of things that are presented as evidence and should be true. And we don't have the science to back it up. And this is just handled at the National Research Council reported on in 2009. We don't have the science behind it. The only programs that have looked at that as far as I know as a research thing have been much more, the four or five grants coming out of the LC program and NHGRI than out of the National Institute of Justice or the other places that are much more closely combined to it. And think about it, it's not just DNA. It would be nice if it were just DNA. On television, it usually is DNA. But you know, it's bullets and it's hair and it's everything that's left at a crime scene. And we need good science across the board and we don't have it. So that seems, that's another domain where I think it's kind of sad that all of that has been left. Okay, you guys in an NHGRI, you have an LC program, you take care of it. That doesn't make any sense. Thank you. Just maybe an impossible question if so. I apologize in advance and in some sense you've sort of talked a little bit about it, but I'm curious in thinking historically 100 years ago about the people that were doing eugenics, I don't think it's probably accurate to say these are bad people or evil or anything like that. This is just sort of the times that they lived in and this new genetics thing that was just coming into knowledge. So I'm wondering 100 years from now, what will the bioesicists of that time think about in terms of what we're doing, how will they criticize us? So two things about that. I completely agree with the first part of your thing, which is I don't think most of the people engaged in thinking about eugenics. When you move from eugenics to racial hygiene to the Holocaust, I think you do cross an ethical line there. But let's leave it at the eugenics, the kind of the Davenport era of eugenics. And think about it, the most famous case in that policy setting domain is Buck V. Bell. It's written by Oliver Wendell Holmes, who's a fantastic jurist. And it is so tragic that the most famous line he ever emitted was three generations of imbeciles is enough. An incredibly stupid thing to say that was factually wrong and morally wrong and completely layered in his legal reasoning. It's only a two-page decision. And it's beautifully written because everything he wrote was beautiful. He's not a bad person. He's a really, really good person who was infused with an ideology that we now recognize as we also recognize slavery was wrong. But go back 200 years, we didn't think it was wrong. And these moral norms are not completely universal at any given time. I don't know, you know what? You're asking a question that by definition we don't know the answer to because I'm caught up in the mainstream of moral thinking. So I don't know what it is that I'm doing this completely evil right now. If I did, I would hope that I wouldn't be doing it. The one thing I will say about that though, and here's where I think this analogy to a windshield is actually apt. I think you're much less likely to make a fundamentally wrong set of choices, policy choices, if you have a bunch of people arguing about it and studying what's happening in the real world than if you don't. And at the time of Eugenics, that was, it was not a robust internal debate. There were voices of dissension and that scholarship's beginning to come out. But there was a mainstream and the mainstream was the docs and the scientists and everybody else was at a lower tier. And I think there is real social value in making sure that you're much more systematic in thinking and you aren't engaged in group thinking of a small elite driving the policy. And I think the fact that we have an ELSI program makes it less likely that we might make a tragic mistake like that again. I think a hundred years from now we'll feel that we're not treating NIH Institute directors nice enough on a day-to-day basis festival. We'll look back on that and feel guilty. Go ahead, over here. Yeah, one of your slides that mentioned Jeff Slosh as an unsung hero with a tech dev. But I don't think you really discussed it too much. You're talking, what was Slosh's role and his contribution and why is he an unsung hero? Oh, bless you for that question. Thank you, I skipped over that. Thank you. So here's a problem, right? You have an institution that thrives on R01 investigator-initiated research. Little 1,000 flowers bloom and let science go where it will. And I completely, to the core of my being, I believe in that. On the other hand, here you have a project that's completely dependent on a set of technologies that need to do, you need the widgets to do what you need the widgets to do in order to accomplish the project. Moreover, you know that the technologies that exist to do DNA sequencing in 1985 are not scalable. So you need new technologies. Well, what are you gonna do about that? You need a program that will cultivate those technologies. And yet, you are housing it at the institution. NSF and NIH are committed to external peer review. If you'd housed this program at the Defense Advanced Research Projects Agency, you would have a place whose people wake up in the morning saying, who am I gonna give money to build a new technology to change the world? But they don't have peer review panels, so they have merit review, but not peer review. And that's much more naturally married to the task of getting sequencing machines to go faster and better. And so what I think is amazing about what Bob Strasberg and Carol Dahl and Jeff Schloss and Jane Peterson managed to do was to use the tools that they had at hand, which was NIH peer review, but got the system to cultivate new technologies and new ways of doing things that we would not normally associate with R01 kinds of molecular biology studies. So I think they're unsung heroes for somehow making this bureaucratic process produce the outputs that we wanted with a process that wasn't really designed for that kind of a purpose. I'm not gonna put words in your mouth. I would put my own spin on this. And Jeff's not here, so I can embarrass him even more. I mean, the fact is Jeff and the others were being asked to take on an incredibly high risk endeavor. Many people on the outside thought the government was gonna fail miserably at this, that the private sector would be much better at technology development, and it was gonna require a major chunk of his, and Jeff's in particular, who's still in charge of our program, I mean a tremendous chunk of his professional career for something that most people thought was gonna fail. And just he persevered and it not only did not fail, it's been, it's thrived. And so he's unsung in that he's not recognized enough for that kind of risk he was asked to take. Yeah, I would say a lot of you probably don't know who J.C.R. Licklider is. But he was, I think of Jeff in that same category. J.C.R. Licklider was the guy who became the first program manager and then the office manager of the Office of Computing Technologies at DARPA and gave rise to all of the technologies that we use in these machines. It's unbelievable source of networking and mice and all the stuff that we think of interacting computing. And yet very few people until very recently even knew who he was because it was all behind the scenes. So there's actually a second project that you could use as your N equals two in terms of your LC comment. You could actually, Eric, you could have a seventh talk in this series on the Human Genome Diversity Project of Cavalli-Sforza. And then, because that whole project has engendered a decade long literature on race. So there's actually is a second project where LC could be highlighted. Yeah, and there is a scholarship on the Human Genome Diversity Project. And of course, Jenny Reardon's book on that is basically the first chapter in that history and it has a pretty bad outcome. That is it didn't work out so well the first time around. But of course, since we're studying human genetic variation, the technology is just so amazing. Look, isn't it unbelievable that the kids that have been born in the last 10 years are gonna know for their whole lifetimes that Homo sapiens and Neanderthals interbred. And we didn't know that until very recently. And the reason we know that is because of studying the DNA. That's just, this is like cosmology. This is like the big bang stuff, as far as I'm concerned. And so the Human Genome Diversity Project is something that's gonna unfold over time. It had a really rocky start. And yes, it's one of the areas that we have really had to concentrate on is what does this word race mean? How do we use it? When do we use it? And it's an incredibly slippery term that has both biological and social meaning. And we work back and forth between them all the time. And that's worth its own five or six lectures. Absolutely. Well, I think with that enthusiastic and I want to say thanks Bob for a very stimulating conversation. Thank you, sir. Yeah, thank you.