 Hello, everyone. It is now spring of 2023, which means we are in the midst of celebrating the 20th anniversary of the completion of the Human Genome Project, a major milestone in the history of science. The story of the 13-year Human Genome Project was one of great accomplishments and in many ways incredible audacity. In reality, the Human Genome Project consisted of many smaller narratives, some scientific, some political, and some sociological. Some of these narratives have never been told, or at least not told in much detail. Now one such narrative involved the efforts of five genome sequencing centers who were closely together in the Human Genome Project's final stages, a group known as the G5, a name affectionately used to mirror well-known groupings of countries, such as the G7 political group. Of course, there were some who might have falsely thought the G part of the name stood for genomics, but it didn't. In this video conversation, we aim to highlight and even uncover new insights to the story of the G5. For the first time in many years and in honor of the 20th anniversary, we at the National Human Genome Research Institute have gathered together virtually, of course, the G5 for a reunion. To toast the 20 years of great science sense and to share stories that couldn't have been told back then, we are here today to hear from those who participated in the G5. Before I introduce my guest, let me provide a little bit more context to this. As the Human Genome Project pursued its last and most difficult goal that is generating the first sequence of the Human Genome, there were groups around the world contributing to that effort. In fact, by the end of the Human Genome Project, something like 20 different countries contributed to the generation of that first Human Genome sequence. To effectively get the job done on time, it was decided that a small group of people from the largest genome sequencing centers would need to take the lead to make sure the goal of sequencing the Human Genome was completed in an organized and a coherent fashion. And at the end of the day, five such centers produced the largest amount of sequence data came together, hence the G5. The G5 worked very closely together in the final stage of the Human Genome Project to generate most of the Human Genome sequence to ensure that the Human Genome sequence produced was high quality and to organize the worldwide effort. And of course, the importance of this achievement cannot be emphasized enough. The first Human Genome sequence was the signature accomplishment of the Human Genome Project with its successful generation representing the project's finish line. With that background, let me introduce my friends and colleagues representing different parts of the G5 who have joined me for today's discussion. So first, Jane Rogers, then at the Wellcome Trust Sanger Institute, previously known as the Sanger Center in Hingston, UK, along with Michael Morgan, then a leader at the Wellcome Trust. Second, Ari Petrinos, representing the efforts of the Department of Energy's Joint Genome Institute in Walnut Creek, California in the United States. Third, Eric Lander of the Broad Whitehead Institute of Biomedical Research at MIT in Cambridge in the United States. Fourth, Richard Gibbs, Baylor College of Medicine's Human Genome Sequencing Center in Houston in the United States. And then fifth, Bob Waterston, then at Washington University School of Medicine's Genome Sequencing Center in St. Louis in the United States. And of course, any outstanding group needed a leader to drive them to success, and that key leadership was provided by Francis Collins, then the Director of the National Human Genome Research Institute, or NHGRI, at the U.S. National Institutes of Health. Well, welcome to each and every one of you, and thanks for joining me virtually today. And let me just immediately say we all look just as youthful as what we looked like on the final day of the project 20 years ago. So with that incredible stretch of the truth, let's pull back the curtain and discuss the true unfettered and untold story of the G5. Now, memories are, of course, not always complete and they could morph as the years have passed, but that's why I think it's wonderful to have all of you, because the group as a whole will provide a check and balance to the facts. I will welcome anyone to speak up when your memory is different than any other person. And I will be the moderator and the host for this conversation, and I have my cup of tea here and I am ready to go. So to start, let's discuss how the G5 came to exist and why its creation was so important. So thinking about that, tell me, what was your memory? You know, our history archive that we keep here at NHGRI shows that February of 1999 was the starting point for the G5 group. Does this ring true? And other people's memories? No. That sounds really late. So we believe that it was around February of 1999. If that's not the case, I don't think that's the case, Eric. Okay. I think the first time we got together was in December of the preceding December. Hmm. And that was an important meeting. John had sent off his infamous friendly fire note about a month before that. And I think it was that the realization that people were going in different directions that led to us getting together, John was summoned, as he put it, to appear before the NHGRI advisory council. So he was coming to Washington. And I think there was a meeting of the five of us or the five centers that was associated with that. And Bob, do you think that Sulston Salvo was the trigger that led to the creation of the G5? Or was it just the facts, the way they were coming together at the time? That was the trigger to create the G5? I mean, the G5 was really created by funding decisions, right? I mean, in essence, the fact that the three U.S. centers represented here got the bulk of the NHGRI funds. And the Sanger Center had its commitment from the Wellcome Trust. And the DOE had committed. And so it was clear that those five groups had the bulk of the resources. So I think that's how it settled on five. But Francis, can somebody else? I think Bob's memory is better than mine in this circumstance. But I certainly do have a clear memory of the friendly fire message, which got quite a bit of attention well beyond our community of genome sequencers. Man, certainly did point to the need of having a mo-core here and plan amongst the major producers of sequences. Just a little background here, Eric, because people jumping in on this may wonder, well, what was going on before that? We had quite a gaggle of genome sequencing centers involved, starting back in about 1996 when it became clear that you could actually start working on the human genome. We were all encouraged by the successes that were happening with model organisms, particularly what Bob and John had done with C. elegans. But it was kind of a gaggle. And as you might expect, some of those centers had grand ideas, but didn't really kind of live up to those. Before the G5 really fell together, we had 20 genome centers that were contributing in some way. And that was impossible to manage and to hold everybody accountable. So the notion that we had to kind of get serious and take the five centers that really had the capacity and turn this into a production-minded effort, it was time. And I guess even though that letter from John was sort of painful, especially to me, it got us in a good direction. But Francis, I would chip in here and say the stimulus to get to really get going and concentrate was really provided by by their announcement that they were going to work on the human genome project. At the Sanger, we'd already been in to ask for increased funding from the Wellcome Trust. It was actually prior to that because of having met at one of the, it was the third Bermuda meeting. And at that point, our perception was that people really weren't focused. They were at C and we needed to up our ante to from a sixth of the genome to a third of the genome to get people to take notice and start to chip in if they wanted to join in at all. So, you know, that I think, you know, at that point, things started getting moving, but Salera's announcement that they were going to do the human, I think that was the catalyst to, you know, get us thinking about how we would go about doing the sequencing. And there was a meeting at Erlie House, not long after the Cold Spring Harbour meeting, that I think focused on what could be done, how should it be done, and what should the product be? My memory is that the crucial thing that really was catalytic was in fact the formation of Salera, in the Cold Spring Harbour meeting that I attended with John Solston, at which we announced that we were going to sequence, pay for the sequencing, the Wellcome Trust, of the whole genome, even if the American partners left. In my mind, that was the thing that really focused minds, and we then had to be properly organised to get the job done. And that's when it moved from individual labs doing their thing to really a coordinated industrial activity. That's my memory. So Richard and Eric, I saw your hands go up at different times. Do you still have comments? I'll just add one thing that you may or may not recollect. And I think between that May meeting in 1998 and the Salera announcement and all of those events that happened before the March 1999 gathering in Houston, I think that's what we could have a lot of conversation about. But at the meeting in Houston, we weren't funded yet. I think the process of refunding was happening, but there were no official announcements, so we could not declare ourselves the anointed group to be supported to finish the job. But nevertheless, we came together to discuss the principles. And that was the tenor of that meeting. So to me, why that meeting or even one after it was the first official G5. But no doubt we all coalesced after our fund meeting in May of 1998. Eric, you want to add to that? Sure. I think trying to figure out when the G5 started is hard because the G5 means many different things. I would date the G5 to several years earlier in the sense that it was becoming apparent that there were five centers that were prepared to take serious responsibility and who intellectually respected each other. Not to say we didn't fight with each other and all that, but there was a lot of intellectual respect and responsibility. And I think Francis's point about the original Bermuda meetings, when people showed up from all over the world and made land grabs for, I'm going to take this part of the genome and I'm going to take that part of the genome without necessarily being able to back it up with the confidence that they deliver, represents the tension between a project that at its core is trying to be inclusive of everybody in the world and at the same time has to get a concrete job done. And so I would say there was an evolution from early Bermuda into a little later and then kicked into gear of we must actually put ourselves on a deeply organized footing as time went on and particularly with the Solera announcement. But I would say that G5 was not created in a big bang, but coalesced out of the inchoate original genome. And it has lessons for how such projects should be organized because had that had been designated at the beginning of who was the G5, it wouldn't have been as good as if it evolved in the way that it did. And we're going to get into that in a couple minutes. Actually, I want to ask two more questions before we move on. One is just a simple question, although I'm not sure we'll remember who named the G5 and coalesced. I remember that, but at some point that became a word. I mean, that became a phraseology. Eric, you remember? Yeah, I at least, of course, we can all compare memories, but I like giving things cute names and so I remember having said, this was like the G7. Now, somebody else may have said that too, but my recollection was it was one of these cute names that we we tossed out in passing as a semi-joke and it stuck. My recollection is we started off with the G15 that was inclusive and we then had the G5. I think Francis made this comment, the G5 was the Security Council. I think I did. And I think it was the G20 was the overall group, but I don't think we named the 20 until we already made the five. Yeah, we had the five and then what are we going to call the rest of them? Okay, they must be the G20. That was my recollection. And that actually leads me to my last question in this category. I'm going to direct this either at Michael or Jane because there was there were G5 had four US components and one non US component. Michael and or Jane, did was that sort of difficult in terms of was there adequate international representation? Did you feel it was too US centric? It ended up that way with the collection of five. But what were your memories then or now in terms of making sure there was that right balance internationally? I think some of John's excitedness came from feeling at times that if we haven't been as big as we had been, you know, whether we would actually be a part of it at all. But we were very conscious, I think on our side of the Atlantic of the need to represent the centers who were left out of the G5 when that formed. There were centers who had been working really quite hard to try and get, you know, the funding needed. Jean Weissenbach in Paris for one, Sakaki in Japan. And I was I was very conscious that what we shouldn't be doing is doing something that would exclude them in a way that was detrimental to the project. Yeah, go ahead, Michael or maybe Michael first and then Ari. I think you have to include in this the meetings that we had. We went around the countries. So we went to China. We went to Japan. And so there was always this bigger group that were kept informed. That's why I've used that term of the Security Council as part of the United Nations. Ari? I had the notes to back it up about how aggressively I fought to make sure Huanmin Yang and the BGI that was there at the early stages played a role. Of course, they did sequence a few things, but it was pretty trivial. But it was important that the country like China be represented significantly at the at the table here. Indeed. I also worked pretty hard to try to be inclusive of Huanmin Yang and his team, which started from a very relatively rudimentary state and scaled themselves up very quickly. And look what's happened. China has become so remarkable in genomics from that early start. I still, I mean, even in this current today's climate, I'm very, very close and working closely with Huanmin Yang. So the record is it's Huanyang Ming. But anyway, I just wanted to echo what Jane said. I mean, I had lots of conversations with John where he was very worried about the U.S. centric nature of things and whether the U.S. was just going along on its own and making sure that Jean Weissenbach, Andre Rosenthal and so forth were included where we could. Richard, you were going to make a comment? Oh, yeah. You know, I wrote a small piece a couple of years ago about the project that's many of us have. And I kind of rushed it out. And I think I've got one thing right and one thing very wrong. The right thing is that I called it the human genome project changed everything. And I'm kind of proud of that sentence. But what I've got really wrong was not emphasizing the community and just how strong what everybody's talking about, how much that contributed to the way that I think we all think about science. And like some of you, I'm still close with Henry. And it would but for that, that connection would not be there. And I wonder what we can do to if we rekindle anything, it would be that sense of international community. I agree. So a couple of you mentioned in describing how the G5 formed the importance of getting it right in executing a big science project, like the human genome project. And a couple of you alluded to the fact that we really did learn some lessons about how to do this right. And so I think it's worth discussing a little bit about how the G5 actually interacted. Because I think it helps illustrate what might be necessary in other big science projects that have taken place since then or might take place in the in the in the future. And you know, how do you even coordinate all of this when there's so many people involved. So my understanding and I never participated in a G5 call. I was in a different stage of my responsibilities at NHGRI, but I heard a lot about it. And I then and I heard a lot about it recently is that is that you would mostly meet by conference call a couple times a year, you would try to have face to faces that it was decided that the every conference call would take place or the great majority of them would be routine to have it on Friday at 11 o'clock Eastern time, which ironically is exactly the time we scheduled this call and in part to deal with different time zones and the various participants. And that was very regimented. So I'm seeing heads nodding. So I think I got those facts right. I guess what one of the questions I have is, you know, who decided and how was it decided? Who could join these G5 calls? What were the rules for having additional people join either at the designated sites or guests? Or were there always other people? I know that some databases were invited to join at least some of the calls. How were those sorts of decisions made and coordinated? So I'll jump in. And much credit here to Mark Eyre, Jane Peterson, Chris Wetterstrand, who were part of the team to put those calls together every Friday. And yeah, I still have an anxiety attack occasionally on Friday at 11 o'clock. But oh my God, are we ready for that? G5 meeting is the agenda ready to go. One of the things we tried to do was to make it scientifically interesting. So there was at least for some of the meetings, the first half was a lab meeting where one of the G5 would have something they wanted to talk about, maybe a new sequencing technology or a new assembly or some new insight about the genome. And then we'd get into the really nitty gritty. And a lot of what had to happen was to develop these tools that allowed us to assess production on a day by day or at least week by week basis. And those were not trivial to put together, but then that became understandably a big focus. Are we on track? Can we project where we're going to need to get to in order to meet the goals, especially with the Solaris threat? And what do we need to do if one center is maybe a little ahead of where they thought they would be and somebody else is a little bit behind? Could we do some shifting of territory to try to make sure we get the whole genome done at the same time and not with some places that we're still falling behind? All of that had to kind of fit together. So I think Mark and Jane and Chris and I would often be the ones to try to figure out what the agenda was going to be, but it was very much a group kind of decision about what are the most important things. And we would often end I think each talk with a each meeting with a sense of what should we talk about next week that needs particular attention right now. It was super intense. It was super collegial. There were times where there were some butting of heads because they're no small egos, including me and in the G5 community. But I don't think there was ever a sense that we were anything other than completely united to achieve the goal. And Francis, did you moderate this like, you know, you're the one that cut people off and it was always an hour? I mean, was all this pretty tightly controlled? Pretty tight because people had lots of other things they were doing. And yeah, I guess that was my job. And I'm not sure whether I was very good at it. I'd like to hear from some others who, you know, were was it good the way these agendas got formed? How these meetings got run? I want to know when we actually started calling. So I have the memory of the December meeting and Richard's right. Another big step. When did we start actually having weekly calls? It was pretty soon in the face-to-face, right? I assume it was shortly after Houston. It must have been when the funding was announced or something like that when our self-designation as the G5 became more legitimate. Jane, was that your memory? Yeah, I had a feeling that the calls came later, that they didn't really start until autumn of 1999. I think we really got going when Solera announced that they'd sequenced the fly and were turning their attention to the human, because at that point we really had to accelerate and that I think was a real stimulus to go to these, to the weekly calls. Before that, you know, we had face-to-face meetings. I think what would they be there? Would they quarterly? We think face-to-face were roughly twice a year. That's what our records show. Sometimes they were three or four times. I thought they were like every more often than twice a year. But I really am curious when the calls started on a regular basis. I don't have a fair recollection of that. Eric Green, I thought you said you had minutes of the first call and you were saying it was something like March of 1999. Did I make that up? We don't know. We're scouring our database. We're literally looking at our archives now. Well, there was a difference between where we have evidence where the G5 being referred to as opposed to call minutes. So that was the distinction. We have records of the word being used, but honestly a call minutes. I have a little different recollection of the calls that Francis did. I think they were, we were clearly united in having the goal. But I think the meetings were often very contentious. And there was a lot of back and forth between the groups about who was doing what and why we were doing it. And they were vigorous discussions. I'll accept your amendment. They were in I'm in with Bob on this. And that's what made them so good. I mean, you know, Francis said they were strong egos. I think they are true. But I think the important thing was there were strong views on what was important, how to do things. And those arguments, which were, you know, strong and sometimes heated, were about principles and different approaches and things. And I think because it was a collection of five super smart centers that had opinions about the ways to do things, you know, I think this was a little strength to the human of the public human genome project was it was not a monolithic point of view. And by the time we were done with a couple of weeks talking about something, we had moved each other, you know, somewhat we had said these kind of data are needed. And that's frankly why I love the G5 because you always got off, you got off the phone exasperated sometimes, but you always got off better, you know, from having having hashed stuff out, even if you didn't necessarily want to admit it every week. I was going to say that's that's in hindsight, I can I can accept that in hindsight, in hindsight, but Michael, you had a you had a comment. Yeah, I have a slightly different take on this because the British effort was in no way competitive with any other British effort. It was the British effort. And there was only one source of funding, there was no competition for funds. My recollection is that there was a lot of competition amongst the US big labs for funding and for the rest of it. So I think the British end of it was in a slightly different position very privileged really, they just had a tap at the work and trust and it was basically on most of the time. I agree with Michael. I didn't feel like that. You weren't supposed to feel like that. Well, you know, I guess I weigh in a little bit with Bob and Eric, but I think we had some spirited conversations. I want to say that I learned a lot from the process in how the rest of my career and what working life has unfolded. It's okay to have ferocious discussions if you've got strong leadership and a willingness to execute or make a decision and have everybody execute on it. And that's what we had, I think we had a leadership that and a structure that allowed we knew no matter how much we argued that sooner or later someone there would be a process things would get decided one way or the other for the argument. I think the other thing is we looked at graphs of progress, real data. So a lot of the arenas we work in now are not anchored to real data and the discussions are all over the place. But if you know veterans look at these kind of meetings and other gatherings and say, well, if we had a graph about what's actually been done, the discussion would be different. We learned that from the GFI. So Francis, I want to endorse what Richard just said there and go back to the first quality assessments when genome centers had a sequence stuff and send them around. I think the genome project really promoted a transparency which was deeply uncomfortable. I hated opening that brown envelope when the quality assessments came back and you saw what your quality had been judged to be. But it was the heart of what made this project get better and better. And then as Richard said, with the graphs going up, real efforts at transparency. So I don't want to lose that as one of the key features of the project overall on the G5 in particular. Yeah, I'm really glad you brought that up because I was going to also wasn't just about how many base pairs are people claiming they have sequence, but are they reliable? And that was quite a complicated process to set that up in terms of this sort of round robin for doing quality assessment. But it was critical. And we learned some stuff about the way in which we were approaching this. If we had not done that, we might be still reeling from people complaining that what we produced was not a quality product. And it was actually a much better than most people thought it could be. That's absolutely correct. I mean, we learned a lot from those things. And in terms of transparency, it made us, you know, when we said things, we knew we had to be able to back them up. We did have a lot of different views about how things were done. We did come together. And I think the reason we came together was that we really did have this overarching goal that we all very strongly shared, that we had to get the sequence there. And we had to do it at the same time as Soler so that the data would be out there for everyone to use. It was not just getting the genome done, it was getting the genome out there for everybody to use for free. Yeah, we're going to come to that. We will actually come a little bit more to Soler in a little bit. Michael, you want to say something before I ask another question? I just want to make certain it's not misunderstood that Sanger was on its own. Sanger benefited enormously from being part of the whole enterprise, the learning aspects and all the rest of it. So if I gave that impression, it's not one that I really want to leave on the table. Right. No, no. Yeah, it's sort of back you up on that, Michael, because we did learn a lot. Yes, as Eric and Richard have already said, it was very painful sitting in those Friday meetings, especially when, you know, people were haranguing us for not doing as well as we were expecting to. We had problems to law. And on the finishing side, I still remember Eric, you know, having more than one go at me for keeping our finishing going when, you know, the emphasis should have been on getting the shotguns through. But so you're living my memory forever for that, Eric. And for the record, for the record, she was referring to Eric Lander and not Eric Greenless. So just one other point on all this, I think, as Michael pointed out, you know, there was a funding competition issue that drove some of the behavioral patterns that you saw. But for a lot of the period, Michael, funding was stable. So it was all the other things, the egos and the scientific genuine, genuine disagreements that drove the vociferous nature of the discussion. I think to Richard's point, there was no way any one center could succeed over the other centers. We had one goal, which if we fail to deliver, we were just going to all fail. And if we delivered, it was going to take all of us. So as much as I remember, we had our friendly competitions or something like that, the major thing was we had a job that we had to get done and we could only do it together. I think you made a new word, Eric. I remember, uh, cooperation. By the way, we did just jump into our history database and we now have more evidence to suggest that the first conference call of the G five was February of 1999. Wow. So February in 1999. All right, I'm going to ask one more question in this area and then we're going to move on. But I can't help but ask it partially because I'm a technology geek. You all dealt you all interacted the most by conference call staring at polycoms, probably. And, you know, the world's in a different place now with with virtual connections that include video like we're doing now. I'm just curious, if any of you have done the thought experiment, what might the G five have been like? If there would have been video capabilities or this kind of an interaction instead of polycom would have all been the same didn't matter or or it would have been a little different. Less facial expressions and rude gestures, I think. Exactly. The conference call meant we could throw up our hands and screw up our faces and hit the mute button and say something. Hit the mute button and talk to everybody around the table and say whatever you want. It's right. They're politically valuable. All right. So I what I'm hearing is that Zoom would have made everybody behave better. But therapeutically, it wouldn't have been as good that you needed to that mute button to blow off steam. Anybody have anything to add to that before we move on? Zoom call has a mute button to but you can see people's mouth moving unless you're going to turn off the video to reading lips and that might ruin the community sense of working together. But I will point out, I mean, we all laugh about that. But, you know, NHGRI now has major consortia we're running in the way the the groups are interacting is by Zoom. So it's not by conference call. And so there is a new dynamic with these kinds of efforts that your behavior has to be a little bit different because you can be seen. Looking at my screen at my screen, Eric, I see eight pictures. What if it were 25? Would that make it easier or worse? Oh, worse. Would make it worse for me because I can keep track of at least a handful of you 20 would be hard to keep track of. And you can hit the mute button and nobody knows that you've hit it. That's right. That's right. So again, you could be you can misbehave more when it's just the phone. That's what we keep hearing. And you're on better behavior when it's by Zoom. So let me transition because this sort of I immediately started hearing about personality traits coming out from these G five interactions, you know, and as as time goes on the personal side and the personal anecdotes, sometimes of the hardest ones to recover. I mean, we look in our digital archives and we learned a lot about the facts of what happened what got discussed what was concluded. But you don't really get a very good sense of sociology. necessarily, or you have to read between the lines. So I could imagine that and it's true of, you know, any group that is dealing with high powered issues that people take on different personas. I'll give you examples. Some people are optimists and cheerleaders. Some people are pessimists and Debbie Downers. Some people just like to covetch all the time and complain. Some people like to be very funny. They're the jokesters of comedians. Some people can be little rascals and be really bratty. I'd be curious to hear in like one word or one phrase how each of you believe you are characterized or how did you behave on those calls. So Richard, I'm going to start with you. How do you think you were? What was your persona during most of those interactions? I find that almost impossible to answer. But I can tell you that one person at one moment told me I was the nice guy in the genome project and another person within an hour in my local environment told me what an A-hole I was. I think I'll leave it with that. Bob, what do you think your persona was? Oh, I'd like to think that I was the reasonable one in the room. Okay. Jane, what are you about you? I felt that I was sort of the face of the people who were actually doing the work at the Sanger. I'm a listener, so I did a lot of listening. John and I used to take these calls together on a Friday afternoon for us. And when it got particularly fractious, it's not the right word, but stimulating, I suppose. We always had to go to the red line on the way home and the time that we spent there was proportionate to the air. I'm on the call, I think, or the heatedness of the call. So I think I was a listener and a very reasonable person on those calls. I'll let you say, and then I'll be curious if Bob or others have a thought, what was John Sallston's persona? Excitable when there was an issue to discuss. So he was excitable. Bob, do you agree with that? Yeah, he certainly, he had his buttons. Eric Lander, how are you? What do you think your persona was? Well, I'm going to go with excitable and stubborn, which I would agree that John also was excitable and stubborn. And I had so much respect for John, because we didn't always agree on things, but I just always respected. And Bob was the reasonable one. Yeah, Richard might have been the nice one, but Bob was always the reasonable one because he would come in with the calm voice and then bring us back to, we're all in this together. Jane was always incredibly sensible in these things. But I mean, these calls got to sometimes be very excitable. And I think of you as being grounded and sensible in a lot of this. And I think all this dynamic was like really critical. You couldn't just be complacent about your thinking, because you had to deal with your G5 colleagues. I think hearing about all this excitability and so forth, I think I'm right, Francis, that at one point, the calls had gotten so fractious that you called me up and said, what can we do to solve this problem? Because we were spending more time at each other's throats and not resolving things. And I think that's when we started rotating the leadership of the calls. I mean, you were still the moderator or whatever, but then one group was in charge each week. Yeah, Bob, you're exactly right. And I hadn't had a clear memory of it until you brought it back to mind. And yeah, that was what we tried to do. And since you were the reasonable one, I guess you're the one I called and said, this whole thing more reasonable. And yes, we did then start at least the rotation where each group would take a turn in the lab meeting part of it and say what they thought the group would learn from and get us back into getting excited about the science instead of arguing about this curve or that curve or whether we were doing too much shotgun or not enough clone by clone, which tended to be the place where usually things got heated. But yeah, you're right. There were times where it got pretty tense. There were more than one of the people I see on this screen I had to call and say, you know what you said to your colleague, that really wasn't very friendly. So yeah, a little bit of visits to the woodshed occasionally were needed, but not very often. Ari, what about you? What was your persona? I was pretty stressed out because of some of internal DOE problems that were very unique to me that you had absolutely no idea. I was under the pressure for. So that was what I remember the most. The internal problems that I was facing that were understandable. And in fact, perhaps even more difficult than what I had expected. So that's my persona. Okay. And Michael, were you on many of these calls and participating? What was your persona? I think everybody would agree. I was Mr. Nice. You still are. All right. Well, that then leaves just Francis. Francis, what was your persona? I hope I wasn't excitable, but I was excited about the science. And I think mostly I was an optimistic peacemaker. You were frustrated about progress. Oh, yeah. Yeah. And sometimes that came through. Well, yeah, because we were all on the line, of course. This was not a place where failure was an option. I remember going to Richard to that meeting that you held in Houston, and I brought with me an entirely new proposal about how the G5 should get the job done, which I hadn't even discussed with my staff. I sort of had worked on it my own head over a couple of days. And the room blew up and people were not sympathetic with this approach, which was very much along the lines of doing more hybrid and less clone by clone. Eventually we figured out what to do. That was a feisty part of the discussion, Francis. I remember your opening speech though, which was Churchillian. Do you want to recall it for us? Yeah, Churchillian would be very kind, but it was one of those like we are at the moment here. And this is the precipice that we might either succeed or fail. And we have got to reorganize our approach. Because if we continue on the current path, just mark it out here over the next few years, we are not going to achieve what we have promised to do. I remember when you're going through hell, people are going. I still use that sometimes. But Francis, because this is archival here, when you say if we keep doing what we were going to do, we would not have achieved what we wanted to achieve, what exactly do you mean? We would have achieved the finished sequence. So we set the right goal and we stuck to the right goal that we're going to finish the sequence. And a lot of the arguments we had were about order and what we needed to have by a certain date and a draft and things. And I agree with you that that was in the end a critical decision on the one hand to say, because we had a competition, we had to have a draft product out there early. But in the other hand, everybody holding feet to the fire saying, and we must swear to each other in blood that we are not giving up on the goal and the timeline we had set. We're rearranging. And that was something where there was a lot of worry in the group, particularly in the part of some, that we would not actually hold ourselves accountable to finish it. And so I think we would have gotten the thing done in the same time frame, but I think we would have lost in the court of public opinion had we not done it. And it was great to balance those. Point very well taken. And I also get riled when people say, well, it's only because of Solera that you guys actually finished the genome project in 2003. That's simply not true. But the trajectory we traveled was altered. Yes. By the way, before we move on, Ari, I can't help, but I feel like I was baited a little. You said there were some DOE issues that were making you nervous. Is there anything you can tell us that maybe you didn't want to talk about then, but you feel comfortable 20 years later, setting the record straight? Of course, you know, it may take a longer conversation. But in short, my colleagues, competitors within the Office of Science for the Department of Energy, couldn't wait to see the human genome end so that they can use the money that was funding it to fund some of these other much less important projects. That was a real problem that, in fact, at the end contributed to my leaving the Department of Energy. I just wanted to follow up. When you say end, they didn't care how it ended. It's just done already. Is that right? They just wanted, they didn't worry about whether the project was actually finished or not. They just wanted your participation ended. Correct. We're going to move on. Some of the discussion earlier about the creation of the G5 and some of the major values of the G5 were very much intertwined with the presence of Solera. Also, this notion that we had to get the sequence done at least at the same time and we had to get that sequence shared. There was just so many aspects about Solera coming on the scene that were the antithesis of what those of us involved in the Human Genome Project thought was important and valued. We really need to make sure we talk about that more directly. To stimulate that conversation, I can't help but I'm going to just show a photograph. I took this photograph and I'm going to share it. To me, to this day, when I looked at this photograph as recently as yesterday, I have an emotional wave that comes across and the photo captures it in part because I was influenced by this because I was part of working with Bob Waterston and Rick Wilson and others at WashU. This is an example of a photo really telling a story. Interestingly, the camera I was using even put a timestamp on this. This was, maybe many of you recognize, this was a photograph in the dining room of Cold Spring Harbor Laboratories in May of 98 during the Cold Spring Harbor Genome Meeting. I think the timestamp, I would have guessed this was sometime in the middle of the night, the timestamp, I think it's 1 a.m. and it's just not a zero after the one, but I'm pretty sure this was probably 103 a.m., maybe a 38 second sign like that. You could just read people's faces and body language. You see on the right Bob Waterston, whose just legs were incredibly muscular and handsome at the time. It's so clear he was in great running shape then. Sitting next to him was John Sulston and then you just go around. This is basically the WashU contingent. You can see Rick Wilson, Stephanie Chisholm, Elaine Martis, Marco Mara, John McPherson, and I was there in part because I tended to hang with those folks even though I was at NIH at the time. I was collaborating with my old friends at WashU where I had come from. Boy, doesn't that picture just say a lot about, and I will just tell you that every one of the people except for John and Bob were fairly early in their career and felt that in some ways their career was being jeopardized because of the threat of what was happening because everything negative about the human genome progress was coming to the fore. We were all worried. I will tell you that Bob and John were cheerleaders. They really spent hours, I don't know how many hours we spoke there, and cheered us up and just said this is not the end of where we're going to figure this out. We've got to rally, blah, blah, blah, blah. Let me start by asking Bob, since you're the only other person in this picture, is that your memory and what do you remember about that evening, that time, that discussion? This is probably the first night of the meeting, maybe the second night after Craig had shown up at the whatever it was meeting that happened the two days before. Craig showed up and took Jerry Rubin aside and said he was going to do fly. And he presented his plans for the genome project in front of everybody. We asked him lots of questions. He got prickly and so forth. And the announcement had been made the weekend before in the press. All our people had heard about it. This was the first time that we really had a chance to sit down and talk through what our response should be, what was going to happen, and what we should do. And it was a tough decision, tough discussion, because even within our group, there were lots of different opinions about how we should react, whether we should bother at all. I mean, after all, it was just a press announcement. There was nothing of reality. Craig hadn't done that much as part of the G20. I mean, that's important to remember that he was actually part of that group. And Eric is right that people sat around the table and decided who was doing what. And Craig was sort of on the edge of all that. He wasn't really producing a lot of sequence. And yet here there was this big announcement. Anyway, it was a tough discussion. And you're right, we had to encourage people and bring them along. It was a long night. Bob, do you remember the, I think it could have been that night, or it's the next night, but the Italian restaurant in Huntington, Long Island? Oh, yeah. Yeah. You and me and Francis and Richard, were you there? And John. Yeah. And John. And we had John, because this was, I think, really the G5 before the G5, in essence. And there was this, I forget what the name of the Italian restaurant is, but I'm never going to forget that dinner. We were taking different positions. John was taking the position, just dam the torpedoes full speed ahead. We got to do what we're doing. It's not going to matter. Nobody's going to take it seriously. And because, you know, John can provoke me to take the opposite. I was, I started rattling off notional headlines of what Craig and Salera were going to announce, that when they done a certain number of reads that constituted one X coverage of the genome, they would announce that they had done 67% of the human genome, because it's one minus E to the minus one. And a little later, they would announce they had done 90 some odd percent of the, and they wouldn't have assembled a damn thing. But the press releases, we could envisage what they were going to be. And you, of course, were reasonable in the middle. And we were just trying to, I don't know, you were, you were strong, but not compared to John and me, but, but we were trying to play out how it was already by, within a day or two, we were playing out the, you know, to what extent are we, are we sticking to our guns exactly? And to what extent are we going to adjust to this and what, what was it going to look like publicly and, and all. And it was very intense. So I wasn't at that thing in, in the, in Blackford, but, but I remember how intense it was. And we all left exhausted from, from that dinner. In terms of extremes, I think you're right. John was, you know, we're going to finish this. And we've got, we know how to do this. And we know that a shotgun is going to be very scattered and complete. And it'll all come out in the wash. And I think at one point, you were actually advocating that we should do exactly what Craig was doing. We should be doing whole genome shotgun so that we can keep up. Otherwise we had no chance to win the headlines as you're putting it. And we explored by the end of that night, all the models already that, that we were eventually going to do was, did we have to really do the finishing on it or something? We explored a great deal. And I don't know if I was being reasonable, but I think John, maybe because he, he did have a privileged English position was much less worried about the public opinion aspect of it. And in the US, you couldn't not be aware of that. And I, I'm just curious at some point, Francis, maybe you can tell us some of the, something about the pressures you were facing on that front. Oh, they became intense. So yeah, I'll just tell a quick story about how I learned about the announcement of what became called Solera was I get a note saying Craig Benter would like to talk to you on a Friday night. And that's unusual. And ultimately we figured out I was on the way to Los Angeles for some weekend thing. And so we would meet at Dallas airport in one of those airport lounges. And I turn up and here is Craig, but here is Mike hunkerpillar. I don't think we all quite realized how far down the road that relationship had been. And actually hunkerpillar did more of the talking than Craig did. And I began to realize this is probably a pretty serious endeavor. This is not smoke and mirrors, which I might have otherwise expected from Craig. So I went to that, I got on my plane to go to Los Angeles and who sat next to me for five hours, Mike hunkerpillar. That was a nightmare. And pretty much the whole time told me all the reasons why the sequencing capacity that they had developed at ABI was going to make Craig Benter's dreams come true and then some. So I became very seriously worried that this was potentially a real threat. So when we got to the Cold Spring Harbor meeting, first a G five conversation where Craig talked and got, as you say, a little bit ruffled because we didn't all applaud. And then that meeting in the restaurant, which I do have an intense memory of and particularly came away from feeling very troubled because we didn't come up with a plan. I kind of thought maybe in the space of a couple of hours over Italian food, we'll have a plan, but we didn't resolve it. We had these options. We could do this and they were pretty wide in their approaches and they were not coalescing. And I really worried, my gosh, is this the moment where our public project is going to stumble and we could not afford to you ask about the pressures? Well, shortly after Nick Wade's Sunday morning, big front page New York Times piece, Congress was immediately like, Oh, so what's going on here? And maybe maybe we don't need a public project anymore. This is a good thing. The private sector is going to take care of it. They generally missed the point about access to the data until it was hammered repeatedly into the stories about this. And just after much back and forth, the person that we should always recognize who we just lost the last six months or so, John Porter, the Republican chair of the House Appropriations Committee that oversaw NIH became a total convert to the importance of the public project, continuing and even expanding its work. And that's exactly the way it came forward. If it had not been for Porter, we could have been in a lot more trouble. So can I follow up on that? I mean, you say Congress, but was it, did Porter call you up and say, well, what are you guys going to do? Or are you no longer necessary? It's a usual dance, usual dance where I figure I got to go see Porter who I had a pretty good relationship with. So you figure out how your staff talks to his staff and gets him to ask you to come and do a briefing because you're not allowed to just go knock on the door. And that's what happened. He had previously extended his support for genomic approaches even allowed himself to be considered a lead, a white knight for us on this. And so I was hoping that he would stick to it. And that meeting was very clear. And then subsequent hearings of the Appropriations Committee, he made it really clear as the chair that he was going to continue to be a big supporter. For people who are listening in 2023 or years afterwards, it should be noted that John Porter Republican of Illinois was doing this. And this was an incredibly bipartisan thing. Managing species. I know John very well, actually babysat when I was at Northwestern. I had him from from another point of view. And I agree with you, Eric. It was a very unique individual, the kind that we don't have anymore. Before we move, before we move on, I'm just curious to hear from Michael or Jane if sort of to get the UK view of Solera, was it pretty much aligned with what the folks in the US were we're seeing and what they're saying now? Or was there a slightly different view about Solera? I think working so closely with John, the main concern for us that came across was that the American project funding would stop. The support, if Congress said that didn't need it, Solera would do the job. Then we were concerned about what was, we were really worried about what we were going to do and what was going to happen. But as Michael said earlier, the Welcome Trust had already, just complete coincidence, the Blackford meeting coincided with us being at the Welcome Trust, having our sort of grilling session about our increased funding. And Michael and John went straight from that meeting to Cold Spring Harbour. And Michael stood up the next morning because he obviously picked up what the atmosphere was and said the Welcome Trust will fund the whole project if there's going to be a problem. I have not heard that before. I don't know whether you actually had any authorisation for that, whether you made it up on the spot. But Michael, you can comment. This really was an extraordinary time. I was travelling in a taxi to solicitors on the Friday afternoon where the news came through of the Solera thing and that weekend was one spent running around trying to sort out what could be done. And it was for two-iters that the Welcome Trust had been one of their regular meetings on the Wednesday of the following week when we were looking at budgets. And with a little bit of hazzazz, shall we say, we ended up with getting the governors to agree that if necessary they would fund the whole project and they told me to go off until the community at Cold Spring Harbour, that's what we would do if it were necessary. The public programme could not fail. That was the message. And I think it was one that righted the ship, whether that's an exaggeration on my behalf or not. I don't know, but that's the impression I've always had. And I'd be interested for others to comment one way or the other. Oh, it was a huge shot in the arm, Michael. It really did change the dynamic from feeling sort of beaten up and knocked down into, well, damn it, we're going to do this anyway because Michael has said we can do it. You remember Craig's idea was that Solera should do the human and the public can go on and do the mouse. Yes. And that we all understood was a way to guarantee a data monopoly by saying it would be wasteful for the public to do the human also. And it was a transparent part of a business plan. So I think we all knew there was no chance, not just that we would get delivered to the public later, but there was a real risk it would never get delivered to the public. And so for what it's worth, this was not an ego-driven competition. This was like the strongest way in which we had to defend what the purpose of public science was. And I think it pulled us together a lot, that there was no way we were going to stop this project. So I have a question for Francis. Then since Francis, I just learned you spent that five hour flight with Mike. And part of the history of this is that the James Webber model with Gene Myers presentation all the way back at the Bermuda meeting finally got published in genome research. And Mike told me that and James told me that Mike had read that and in discussion with Michael Tony White. I came up with Solera as the model that thought it would work. And then they reached out to Craig and said, would you be our front man for that? So my question really is Francis, in your discussions with Mike, did Mike have much of an opinion or thought about all the nuances of data ownership, data release, all that stuff? But my impression was Mike was more about, he was more sort of in the spirit that we had, which is let's get this project done with the best thing we can do it. Exactly. No, he did not seem to have much nuance about just how critical it was going to be to have the sequence public in the same way that the public project had been doing. And I think Craig was probably pretty good at kind of covering over the seriousness of why the business model was not going to make that kind of public accessibility possible. Hunkerpillar is much more interested in the technology and I vaguely remember him talking particularly about it being influenced by that Gene Webber paper. And it's almost like Craig was like a convenient partner to get Mike Hunkerpillar's dream to come true. I feel it's important for us to remember because I regard Mike as one of the heroes of the whole program for all the things he did. And, you know, his role in Salire I think is probably not the one we want to reflect on most of all, but in fact that was where he was coming from. And of course, he didn't find being an arms supplier to both parties, let's be clear about that. Well, he thought it was almost the arms builder, you know, that the guy designed it too. Yeah, no, he was the designer. So that's correct then that he sort of saw the Myers Webber paper and thought that with his new capillary machines they would have the firepower to do it. Yep. Well, there's another little twist in this because of course, Jim's presentation at Bermuda did not go over well. And he tried to have that manuscript published in Science. It was rejected. I visited him coincidentally the next month in Wisconsin and suggested he send it to Genome Research. It was reviewed and thoroughly bounced by Phil Green. And the editor said we can't publish this. And I convinced everyone. I don't know if you're on board by then, were you? No, I was. And I actually remember that we collectively or some subset of us came up with this idea of making it into a point counterpoint. Yep. So there's papers on that if here in Genome Research and that's what Mike saw. So what's again, for somebody 20 years later who's listening to this or even further in the future, what's hard to appreciate is it was really an open question at the time. There was no question that if you had a genome that was all unique sequence, you could shotgun sequence it. We knew that you could do it in bacteria because the computer could assemble things. It was all about repeat structures in a genome. And so for a human genome with that much repeat structure, was it going to fall together right without getting all tangled up? So it was a moment that lasted several years where we really were unsure. And we got the answer in the two papers that came out in February of 2001 when the public sequence was vastly better than the Solera only sequence. Now, of course, in retrospect, we now know how to do a whole genome sequence much better by adding in libraries of different sizes and things. But it was an open question that really drove the strategy of whether or not you could or couldn't do it. Eric, your view of that is completely right because I find even now when you talk about the Human Genome Project to young people, they think we had a playbook and they think we just followed the playbook and it was so straightforward. And of course it wasn't. Francis? Yeah, for historians, it would be interesting for people to go back and look at a transcript of a congressional hearing in front of John Porter. I know it was June 16th of 1998 because I got married to Diane four days later, and this was not my idea of a nice way to plan for my wedding. And the witnesses were me, Craig Venter, somebody I can't remember the third one, and Maynard Olson. And John Porter was really quizzing about is this shotgun strategy going to come together for a genome as riddled with repeats as the human? And Maynard delivered this absolutely devastating takedown of the whole approach which turned out to be just about right. I think he predicted, you know, catastrophic failure to assemble 130,000 unanchored pieces, something like that pretty close to what happened. That was one of, and we talked about John Porter, the fact that he wanted to hear that in a public hearing and that it was very effectively taken on by Maynard helped us a lot in the view of the other members of that committee who were in the room. So, you know, we've heard a lot about how Italian food was really important in the early stages of the G5. But I also know that another type of Italian food was really important as we were driving towards the draft sequence. Because it has been written, for example, in Thai magazine, how pizza at area Patrino says townhouse was critically important for bringing together relevant parties to make sure that there was a coherent way to announce the draft sequence of both the genome projects, efforts, and Solaris. So I've read about this in time. I've heard it anecdotally. But Ari, will you tell us a bit about your convening of Francis and Craig in your, I guess it's Rockville or is it Bethesda or North Bethesda townhouse? And what kind of pizza do you serve? I mean, we want to hear it all. What can you tell us? I have to make it a short presentation because we don't have a lot of time. But so I'll try my best to be laconic. As you may know, and perhaps you've been too kind, all of you, not to mention it, I was aware of what Craig was planning to do for quite some time before you did. And that was the understanding I had with Craig, that he would share that information, but that I would not disclose. It was a similar relationship with Francis, you know, at times when I would share some things with Francis that, you know, I wouldn't be telling or Francis would share some things with me that I wouldn't be telling Craig. And I felt as an almost as an outsider. I was not an outsider. It was quite frankly an insider as part of the DOE program. But the DOE program felt to many ways as an outside program to the rest of NIHs. That was something that probably is subject for another story. So I had that unique perspective for both programs. And I know both of these individuals that I had tremendous respect for and admiration. And I felt at the time, and I still feel that way, that both of them were heading towards a collision that was not going to be helpful to any one of the two. So I was lobbying Francis strongly for him to have this off the record meeting with Craig and see whether we could reconcile. I wasn't sure it would work, but I felt it was worth a try. Now, Francis was too committed and loyal to the rest of you that he didn't want to do anything unless, you know, he he got the okay from the rest of you. Craig didn't have that quam. I was surprised that he was willing to do it. But I believe that around that time, he was starting to get really worried that, you know, the collision may have may end up hurting him more than it would hurt us. So it was perhaps appropriate for him and to his credit to see whether there was another way. And these kind of things I've done in my career because of being an outsider on many aspects. So it was worth a try and it worked out, you know, one meeting one evening or multiple. It was several meetings. In fact, there was a if you include the final one where we had the lots of brandy and so on, it was four meetings. But the individuals, the three of us were in fact, three meetings, respect the apropos to the questions you've had earlier. I have all these things recorded on a day to day and hour to hour basis at times. But during this move that happened last week, all these, all these records are in boxes that I haven't yet to open. So as I open them slowly, if there are any other issues that perhaps are left unanswered that the end of this conversation, I'll come back to you all and share them. So Ari tells it well. Let me just go back a little before that. So at the end of 1999, as it was clear we're on this collision course, the public project is really rocking at that point in terms of sequence production. We had our billion base pair Bash and a few other things to document that. Harold Varmas had stepped down as NIH director, I think in November, but he was willing to stay in a role of trying to broker some kind of a peace arrangement between the public project and Solera and there was a meeting at Dulles with Craig and a couple other people from Solera and me where Harold tried to come up with some sort of a way that this could be a win for everybody. And basically it fell apart. Craig was unwilling to make any kind of commitment to anything other than pure victory for himself. Subsequent to that, now with Ruth Kirschstein as the acting director of NIH, Ruth was very worried about the way this looked. Somewhere along the way, I think Bill Clinton said to his science advisor, this is bad, fix it. So Ruth suggested that we have another effort to try to make peace and ask Rick Klausner to convene a conversation with Craig and me and some other folks. That also went very poorly. And after a month or so, especially because Ruth got wind of Craig's behavior, she said, no, we're not going to do this. She was offended by the way he approached it. And I think he leaks some stuff to the press. So now it's getting to be like March, maybe of 2000. And it's pretty clear that we are headed for what's going to be a really messy, awful circumstance in a few months. And I did go to Ruth and I said, look, Ari Petrino has been keeping in close, friendly relationship with both me and with Craig. What do you think about our trying to just in a very informal, quiet, secret way have a conversation to see whether something could be worked out? And she said, what the hell go for it? And that's when we had that first meeting. And I felt bad because I did not tell you other G5 folks that that meeting was happening the first time because I thought it had, you know, 10% chance of making any headway, in which case, why even bring it up? It was only after the second or maybe the third meeting that it seemed like, oh, something might really happen. And we all kind of got into it. That was awkward for me. I felt like this was the one time where I had not really worked with the whole team from step one to try to achieve something. And I guess in the long run, it probably would have been hard to do it any other way. But ultimately, Craig's willingness, because I think he saw the handwriting on the wall for a really bad messy outcome to basically say, let's call it a tie, kind of dominated his otherwise strong resistance to being flexible about anything. And Ari, you helped a lot by being the sort of neutral party who could kind of call him out when he was acting in a way that was not going to get us to yes. I don't profess to have had any great talents or capabilities. It's just being at the right place at the right time and that worked for us. I don't know how the rest of you feel, but I think the outcome was probably an optimum among all different other options that we were facing at the time. Francis, was that was one of the outcomes of those meetings? The arrangement that two publications would go ahead on two products? No, no, that was not. I mean, originally, I had a conversation about having one joint publication. And that was when Kennedy from Science was very involved in their deliberations. But I think the outcome still was a pretty agreeable and successful one, I feel. Yeah, publications were in a later phase. Not much later. Not much. It was July or maybe June. Yeah, the agreement then was to have a simultaneous announcement of a tie. Correct. My memory for what it's worth, the Brits felt betrayed. Yes, I remember. Jane, do you want to comment? Yeah, no, I know this was one time when John really felt that Francis had acted against the G5 and against the Spirit of Collaboration. Yeah, this was John's friendly fire. No, no, that was earlier. That was another topic. Well, that was another one then. But, you know, back to the late 99 meetings that didn't go so well, I was the G5 representative at that meeting with Harold and Martin Bobrow and... Right. Yeah. Who was the... Tony White? Well, Tony White and Gillum and somebody else and Craig were the Solera people. Eric had started a framework with Craig earlier in November. We were frustrated with Eric because he was doing this on his own. But we worked with that and we thought that Solera had more or less agreed to these kinds of things that we went into this meeting thinking that we were pretty close to having some kind of arrangement to hone down the acrimony in the press. And we got in there and it was clear from the start that Tony White had none of this. I don't know, I mean, Craig was sort of in that ballpark, but it was Tony White was just not going to have anything that would compromise his ability to monopolize the sequence for years. That's right. And it was clear that their business plan was to have that sequence and everything derived from it so that they would have control of the annotation and use of the sequence. Go ahead, Richard. I was going to ask you about the timing of the fluctuations in the stock market and its influence because there was a giant market up people, but there was also the Solera moment when after the joint announcement of free data access, how did that tie into the whole dynamic there? That's a piece I've never been able to connect. I do remember that the follow-up to that December meeting led to a letter from Francis to Craig and Solera. And that letter went just before Solera had its stock offering. I believe that's right, isn't it, Francis? That is right. You're remembering something I'd forgotten. And how could you forget that? Well, we're too many things. Well, I remember it partly because Michael's writing about this. And anyway, it was then there was the joint announcement about no patenting and so forth. And then the Solera stock price was going up and up and up. And then they had rumors that they were making a deal and that the intellectual property came into being with Blair and Clinton's joint announcement. And then their stock went down. The whole market went down. There was $30 billion in a day or something like that. Because the White House press secretary got the message wrong in his early morning announcement. There will be no more gene patents for anything. And then Congress got involved and it was a mess. But it was clear that both sides were trying to come up with some kind of way to moderate things. And fortunately, the one that Ari Brokered actually worked. It was the right people in the room. It's just a classic diplomatic solution, which is both sides need a victory speech. The only way you ever get to a peace treaty is each side has to have a victory speech it can give. And that's what this accomplished. You know, Thai was the only way we were going to get there. And I do joke that, of course, there was no data to support the genome being finished that last week of June of 2000. There was no data to support it being a Thai. So it was a data free thing. And I think it was an announcement of the completion of the human genome to many people that allowed us to actually get on and complete the human genome. That's a perfect segue to what I wanted to ask next, which is that we have the June announcement. And then you get the February 2001 publications. How did the G5 interactions change from that point until the end of the genome project? Because it would seem to me the whole focus changed. The salara thing started to evaporate. Was it a whole different dynamic in the G5 interactions? Francis? Sure it is. And let's not skip over the intensity of what happened between June and February trying to put together that landmark paper in nature. And of course, to have an assembled genome sequence that could be appropriately annotated as best one could with a draft. And so yes, a little tip of the hat here to Jim Kent and David Housler for the role that they played to help with that. I think that was a wonderful period actually, scientifically. That was just exhilarating to be able now, instead of looking at the production every day, although we still were doing that, to actually figure out what's in this thing. And the meeting we had in one of them in Philadelphia, really trying to dig through that, a sign who was going to do which kinds of analyses, looking over each other's conclusions and trying to take them apart to see if there was something missing there. That was a lot of fun. And we waited a long time for that. So I don't want to skip that phase, Eric, before we go on to finish the sequence. And can we also note that the papers were originally going to be in science back to back? And there was a lot of G5 debate over whether Solero was going to make their data available as scientific publications should require. And a lot of unhappiness that eventually led us to nature. And I recall the utterly random thing of I was at something New Jersey and met the physics editor of nature around the time we were talking about this. And I asked this person, do you think nature would be interested in the human genome paper? I said, you know, no, just curious. And the next morning, a Monday morning, nature like was all over. We've been already discussing, could we be in science? And so I think that also changed the dynamic of publication too, because I think had they both been back to back papers in science, it might have been a little different. This got the journals invested in a way, and it gave us more space. Because the other party had more space. So I think it was good for the scientific community that nature and science were competing by making territory for the genome, because they had a competitor in a way. You know, how things changed, we Francis is right, we stopped talking so much about production, we still paid attention to that. But the issue became what is going to happen with the publications. And the first was the first issue was when it was going to be published. And John was very much of the opinion that we should just get it out there and get on with the job of getting the real thing, that this was just a transitory thing, and we shouldn't focus too much on it. Eric was on the other hand, of course, John Eric, we're at opposite ends. And so I think we had initially we were going to do a data freeze in July or something really you know, to sort of codify the to justify the June 26 announcement, that we were going to actually have a paper that would prevent it from being completely data free. And but we, you know, I think Eric was was right that, you know, there was just a tremendous amount that we could learn from what we did have. And, and your driving of it was was really a critical thing. Jane, did you notice the change in the style of the calls and the focus of the calls after that? Yeah, the production was one thing, both enhancing the draft, filling in gaps that we needed to improve the assemblies, and making that a focus of what we did. But then it was, you know, getting on to, to, you know, think about how to how to finish it that that's really when my focus came in. But it was certainly, you know, the first the most immediate thing after the June announcement, I think was, you know, what have we really got here? And we I know we all went away scurrying to, you know, sort of find out what, you know, what have we covered? What, what did we need to do immediately to be able to get some analysis done? And as Bob said, John was pushing for a very quick, you know, freeze and publication. I think by the time there was a meeting in Paris, I think in September, before that before Philadelphia, but the Paris one, I think was where John came round to thinking, yeah, no, we can do more analysis on this. I have a question for you, actually. I mean, prior to that, the signers first try of I suppose in the human genome was was to get probesome 22, you know, the finish sequence written up and published in December 99. How much did doing that influence both the push on to get the finish sequence, but also the types of analysis that that, you know, you felt Eric, especially, you know, needed to be done for the for the finish for the draft paper? I think it was very influential, because like, a lot of our issues where we didn't know what the genome looked like, and trying to assemble and analyzing a genome from fragmentary information without a glimpse of better information was hard. And so I think it sort of raised, you know, raised up the categories of things that we should do. And then we asked, how much could we do with a draft in that nodding in that direction? So this is again, another example of where these diverse points of view and diverse, you know, activities, I think informed each other. I mean, I think the hands down lesson is that as unwieldy as some of these consortia can seem, they are so much more powerful because of the intellectual diversity. Sorry, so I can speak to that too, if I may. I think the chromosome 22 paper was beautiful and influential. It set a standard for what a chromosome specific finished paper should be. But in terms of the motivation, I feel like we were all on this autopilot, this phase, we were going to get a finished or essentially complete product done. And so the commitment was there. It was more influential in the sense of how it was presented and what the what the published product would look like. I have a self serving question. How much was the Bermuda meetings and influence on following through with the G5 and the G15 meetings? How influential was Bermuda or not? You're shaking your head, Eric. I never found the Bermuda meetings to be intellectual driving forces. Just saying that I found there were many meetings that were critical, but I thought Bermuda was important for inclusivity and all that. But they didn't seem to me the intellectual drivers of a lot of these decisions, they were important to have. But I think they were important for other reasons. Well, most important of all, of course, the decision to do immediate public data release that when everybody here is Bermuda, that's what they think and they should. That decision was critical, but my recollection is not everybody even agreed to it. The Japanese had issues with this. Yeah, but getting that idea out there is I think the critical thing from Bermuda. When did the April 25th deadline come into place? Because we're all saying, oh, it was, you know, we're all going to get it done. But we did set ourselves another utterly artificial deadline that forced us again. And I don't remember. No, it was the publication of the event. It was not obituary. It was not obituary. No, no, of course it's not arbitrary. It was poetic. It's poetic. It was to commemorate that Watson and Crick pay other. Of course, but we didn't have to tie ourselves to the mass to get to that date. You could have picked another day. Oh, no, France. France was in that. Yeah, I'm afraid you have. And I'm sure he did it so that he could drive us harder. And I think it helped. You think it helped me? What? Okay, we're getting near the end. But I want to, before I sort of ask the final question, I want each of you to think about, is there a memory of the G five experience, either a call or a feeling or or a story or saying that that we haven't said? I mean, I want this to be very brief, but is is sort of in a word or a phrase or, you know, a sentence. Is there something about your G five experience that you have as a key memory, but you haven't said it yet during our conversation today? So anything that comes to mind about the experience, Bob? I don't know that this is about the G five calls for as much, but we haven't talked about the map. And I have to talk about the map because that's what we we put a lot of effort into the map. And and it really was what drove the golden path to a successful outcome. It supplied the clones to us and Eric and others. And I don't know, I think Marco and I calculated he did 63 liters of agarose gels to in the course of a year, the map, the fingerprint, more than 350,000 clones. Ladina worked tirelessly with Jim Kent to feed him, you know, we could essentially fingerprint the sequence clones and and put those on the map. And and that was key for Jim Kent to be able to assemble things. And and it was also what Solera used to put their sequence together. Otherwise, they had 100 they had 119,000 random pieces and they they put them on chromosomes through the STS maps and the fingerprint maps. Yep. Richard, what's what's your memory that we haven't mentioned yet? So I'll be closing out because we're getting to time, right? Just a general comment first. This has been a great discussion about all the exciting stuff that happened up before 2000, but so much stuff happened between then and 2003, which is our anniversary. I wish we had another two hours to talk that through. But the three that will come through that is about the map and the clone availability through from that period in 99 when we changed tactics through to where we arrived at our finished model in our finished pieces and how we pull those pieces together and kind of what happened in between. I suspect that's part of the the ingredients for Francis having to call people and say tone it down on the G5. That was a pretty contentious set of issues. And but anyway, we're celebrating today this completion. The thing I remember and I can't even say when that moment was, there was a particular moment in the whole and when we stopped kind of looking up and saying, what should we do generally and all looked at each other and said, what would it take to get the whole job done? And so this idea of completion as the starting thought for building the model, which to me, that's a product of the genome project. And I don't exactly remember when it was. It was somewhere in 99 or 98. Jane, what's your memory? One thing we haven't mentioned, you know, is the the work that went on to do to get the databases and the annotation pipelines working. This was another diverse activity at Sanger. But, you know, when we came to put that sequence together, yeah, Jim Kent and put up a web browser for you in the US, especially. But the ensemble pipeline was ready to go. It had already put some some data up and it was it was ready. And there was an annotation pipeline that, you know, could work. And that could give us the first view of the the contents, etc. And I think the work that went in that is is worth remembering. But I think one other very quick memory that I've got, I can remember, I think it was the Paris meeting when I met Rick Wilson one morning and he just came up and gave me a big hug. And then he said to the others, he said, you know, being able to hug other people. Okay, I was the only, you know, I mean, well, I'm the only woman on this call. I was often the only woman in the room, both in the Sanger and, you know, sort of at other meetings that we had. But he said, you know, having having a mix and having a different view, having different perspective is important. Eric, your memory. So my my G5 memory, I'm going to say is actually a G16 memory. It was Francis, the National Building Museum. Oh, yes. We had the party celebrating the paper, the publication in February, I think it was of the draft sequence paper. And what sticks most in my mind is that the G5 conversations were also internal and so intense. But coming over to the National Building Museum that day, Lori and I took a cab and the cabby asked where we were going. And I said, we're going to this big celebration of the sequencing of the human genome and this paper and the cabby, you know, turns around and he's, oh, the human genome project. Are you the guys who are giving away the information for free? And it was the moments that I realized, oh my God, they're like people all over the world, cabbies in D.C. who are on top of this, followed it. And despite all the turbulence and noise, they got the point. And I will never forget that cabby. I should have gotten his name. Francis. That's a great story, Eric. My mom came to that particular party a year before she died. And I'm cherishing those pictures of what happened. And we had a band and the band sang some silly genome songs that were written for the occasion. So yeah, it seemed an appropriate moment to get outside of our very focused work-oriented effort and just kick up our heels a little bit. But my memory that I was going to mention is it was an early house. And I'm not sure when this one happened, but it was during the clear threat of whether the public project was going to be eclipsed by Solera. And I remember Bob and John were sitting in a couple of lounge chairs, somewhere out there in the early campus and sort of holding court. And I walked by and we got in this conversation where Bob, you and John basically said, look, Francis, you're going to have to really stiffen your backbone. You're going to have to be ready in the court of public opinion and the media to be able to be the best you've ever been in order to explain why the public project is still relevant and why it matters because of the data access. So don't go soft on us. Do you remember that? I was like, okay, I got the message. I do. And I mean, we talked, you know, Solera had this incredible PR machine. And we had the government upset. I want to hear from Ari and then Michael. Well, for me, the most important memory is the memory of my good friend and colleague, Mar Fraser, who was on my side during all the deliberations. And he, as you may remember, was going through some very serious health problems at the time. But nevertheless, he persevered. He was in the office on a lot of the G5 calls, even though he was one step away from death. I owed him almost all the success if I had any success because he was the power and the force behind the DOE Human Genome Project. Michael. My memory obviously has to do with the famous meeting where the Wellcome Trust announced that they were going to fund the human genome, irrespective of anybody else. And in particular, arriving at Cold Spring Harbour after a long flight from London and going into the bar, and as I said it in somewhere else, people were running around like chickens that had their heads chopped off. Everybody was in a total state of dismay. No, and everybody thought the end had come. And I was the second coming, I guess. So I think I've covered everybody on the memories, correct? Yes. So last question, and I know we're coming up against time. So I want you to answer this question either in a word or a phrase, maybe a sentence. So we're now 20 years past to the end of the Human Genome Project. We've discussed extensively how the G5 played a central role in getting the genome project across the finish line. I want you to think back on the day the Human Genome Project ended, April 25th, 2003. And think about the last 20 years. What singularly, what singularly has surprised you the most about genomics over the last 20 years? Richard, can we start with you? I know it's a hard question. Yeah, it's a tough question. You know, I think the gap between what we know is logical and can be driven by the use of genomics and genetics to understand biology and life and how it's getting implemented and rolled out to the front line. You know, we hope, some of us hope back then, that the whole world would be genetically literate, an amateur of DNA, wake up every morning thinking about that as a part of their lives. And it's taken a while to get there. Jane, what surprised you the most? How much it's already being applied in medicine? Bob? That's a gap. I would say how pervasive genomics has become. You know, we thought about it as the Human Genome Project, and obviously, I thought about it from the worm standpoint in model organisms, but it's just everywhere, in every field, it's driving biology. And I just, I've been amazed at how pervasive it is. Ari, what do you think? Well, you know, as somebody who had to compete almost violently with high-energy physics and the rest of the physical sciences community, it is just so wonderful to see them shoved aside what the Human Genome Project did to biology. It's something I rejoice and celebrate almost every day and look forward to further siding, sidestepping these other programs because we have so much more we can produce. You know, as I like to say, we can almost stoop down and get the gold nuggets that are on the surface, whereas they have to dig deep, very deep, and spend way more money that we can to produce these type of results. I go a couple of weeks ago, a couple of weeks ago, I went to a meeting for the first time in many years in London, Genomics. There must have been two, three thousand people there. The place was stuffed to the gills with new instrumentation, new technology. It was quite staggeringly amazing to me. Genomics is now everywhere. Eric, the stunning thing to me is just how the progress has been so much faster and so much further than I ever could have imagined on April 25, 2003. We talked then about, oh, it would be great to have a reference sequence of the Human Genome and what's unfolded since, the catalogs of all the genes, all the variants, all the RNA expressions, all the cell types, the ability to edit that, the ability in the coming years to find all the programs. I think this concept of a reference and the power of foundations in biology have totally changed what biology was about from the days when everybody was wandering around finding their gene or doing their thing to making it a broadly understandable domain. So I don't think people are going to be able to go back. I mean, my students still ask, how did you do anything before the Human Genome Project? Because they can't conceive of that anymore. So that's what surprised me. I thought there'd be good things, but I had no idea they'd be this good. And appropriately so, Francis, I'm going to give you the last word. Well, so many good words have already been spoken. One thing we have to mention, of course, is just the amazing advance in the technology that that first genome that we celebrated on April 25th, 2003, cost us somewhere in the neighborhood of $400 million. And I know of no other technology that has come down in cost and gone up in quality and gone up in speed. You usually can't get faster, better and cheaper. We got all of those in a remarkably effective way, thanks to all the investments that were made as part of the genome project. And that's encouraged the technology to keep going. And I also, even taking Richard's concern, which I share, that this should have gone faster in terms of the medical applications. I do celebrate where we are 20 years later. Let's particularly say with cancer, a lot of lives have been saved as a result of our ability to sequence a cancer. A lot of newborns have had their diagnosis made clear right away instead of going through many years of a diagnostic journey, odyssey that led nowhere. And let's not forget infectious disease. If we didn't have genomics now spread across the world, including in South Africa and Nigeria, we would have seen a whole lot worse things happen with Ebola and then with COVID-19. Genomics has spread into that space also in an incredibly powerful way. We should not rest, however, to try to be sure that that trajectory goes forward. And we shorten the time that Richard points out, which is still way too long between when we know something will help people and when we actually get it done. Eric, when you make this video, you should calculate how many human genome sequences were sequenced, how many human genomes were sequenced during this call. Just report that to people. And that's another measure of what these 20 years are about. No, I was thinking the same thing, Eric, that we spent how many years and how many dollars and how many people doing this. And you can actually get a whole genome, not 95% of it or whatever we have, and get the whole thing telomere to telomere. And they're doing it thousands. There you go. This was fun. Well, we are at the end. I want to do nothing short of profoundly thanking all of you for joining today and sharing your memories and your ideas and filling in a lot of bits and pieces that we didn't have already about the G5. I will just tell you, as I said earlier, I wasn't a member of the G5, but I was a great admirer and a fan. And in the last 20 years, I've only come to admire each and every one of you even more so. And I'm not at all surprised we had a wonderful conversation. In fact, I enjoy this conversation so much. I've made the command decision, we're going to do this again in 10 years for the 30th anniversary. So please be on the lookout for an email from me in about nine and a half years to get it on your calendars because we'll want to reconvene and see what our memories are like 10 years from now. Totally different by that. Totally different. And we will compare and that's the fun part of all of this. So with that, I will say we're done. Okay, now we could, we're still recording, but now we could be more informal. So thank you all. This was fantastic better than I possibly could have dreamed of. I hope you enjoyed it. And I know we just went a few minutes over. Any last comments anybody want to make? It was fantastic. It was fun seeing you all again.