NEW YORK – Eric Green, director of the National Human Genome Research Institute (NHGRI) since 2009, has been involved with the Advances in Genome Biology and Technology (AGBT) annual meeting as co-chair of the program committee since the early 2000s. For the first time, he will have to sit out the meeting this year, which kicks off on Marco Island, Florida, Sunday and marks AGBT's 25th anniversary, because of a travel pause by the new federal administration that was only lifted a few days ago. As a result, his planned presentation reflecting on the history of AGBT — including photos from each of the last 25 meetings — will need to wait until next year. GenomeWeb caught up with Green on the eve of the conference, long considered to be the premier gathering for the genomic technology field, to talk about how the meeting came about, where genomics is headed, and how the transition to President Donald Trump's new administration may affect NHGRI. The interview has been edited for length and clarity.
Do you have any memories of your first AGBT meeting?
I have memories for a variety of reasons. First of all, I had never been to Marco Island, and so just going to that venue was going to a part of the United States I had never been to. But the other thing, at a personal level, it was the first time we traveled with our two small kids. It's a very family friendly meeting. A lot of people would bring their families with them. All the kids would go on the beach all day while all of us were going to geeky genomics talks.
How did the meeting come about?
It's a little politically charged, but I'll try to tell it in a fairly neutral way. I was going to give a plenary talk at this meeting where I was going to give a 25-year review. I'll give it next year. I have pictures of every single year. I have some photos of people, and wildlife, and everything else. Starting in about 1997, there used to be those meetings at Hilton Head. Craig Venter had a pretty significant control over those meetings, and especially by about 1998, 1999, people were getting frustrated by the way the decisions were being made about the scientific program, overly emphasizing Craig's science and his friends' science, and de-emphasizing a lot of the stuff going on in other parts of the genomics community and the Human Genome Project. That included not just the scientists, it even included some of the companies that were supporting that meeting that were part of the ecosystem. There was one, maybe several companies that decided to donate a bunch of money to something that created a not-for-profit to support the AGBT meeting. It later got renamed the Genome Partnership.
A lot of these companies were being philanthropic in their desire to have a meeting that would be a little less political. So, they said, "We'll put our money where our mouth is." The companies made these donations that created the initial endowment for the meeting. I don't know how it got decided to be at Marco Island, at that hotel it's been at many times, but the rest is history. There was also a genome automation meeting that I think used to be held at the Sanger campus. The first couple of AGBT meetings were cobranded with Genome Automation, rather than having separate meetings.
What was featured in the early years was the final phases of the Human Genome Project. And then it was about finishing the Genome Project and beyond. The meeting got to be really big really quick. Therefore, it attracted a lot of corporate donations, because it's an expensive venue. The other big annual meeting was the Cold Spring Harbor genome meeting, which eventually became the Biology of Genomes meeting. That was sort of the premier meeting early in the Genome Project.
The Marco Island meeting became the technology meeting. Yes, there was a lot of good science. Yes, there were a lot of good applications, but everybody went there to talk behind the scenes, and at the podium, and in the poster sessions, about the latest technologies.
Then what happened immediately after the Genome Project, there was this shift to next-gen sequencing. The good news about the AGBT meeting was, this was the meeting that everybody wanted to go to to learn about the new technologies, to talk to the vendors, to get behind the scenes, to talk about collaborations and beta testing and all this. The bad news was, around 2006, just before next-gen sequencing took off, the meeting actually struggled to survive, in part because Marco Island was so expensive, in part because it wasn't clear whether there was enough new-new for everybody to go to the meeting.
The first handful of years, the meeting easily survived financially. And then it went through about a four- or five-year period where it was really on life support. A couple of companies came in and sort of kept us going with little boluses of money. And then, once next-gen sequencing really hit, once 454 and Illumina came along, it just exploded. And it's exploded ever since. That meant they could make a lot of money to be able to support the meeting, and it also meant that not everyone could get into the meeting, because you couldn't get big enough venues.
The meeting has grown considerably, and it's had various things happen to it. We had to leave the venue in Marco Island for a couple of years because they were renovating the entire complex, and then that got delayed. And then just when we were supposed to go back, a hurricane hit, and that set us back another year, and then we finally got back. The problem now is it is so exclusive, it's too expensive. So that's why we don't do it there every year; we only do it there every five years now, but we always kept it in Florida. In the intervening years, we moved it to Hollywood and Orlando, and there are other places in Florida. So, it's become a Florida meeting instead of a Marco Island meeting.
Probably about 10 years ago, at a stage where we were making huge amounts of money off the main meeting, the Genome Partnership decided to spin out two additional meetings [AGBT Precision Medicine and AGBT Agricultural]. The other reason we did this was because there was a lot of genomic medicine, a lot of agriculture, a lot of cancer research coming to the meeting. We wanted to keep the main meeting technology-focused, but there was so much hot stuff going on. So now it could retain a heavy technology, data science focus, generic genomics, as opposed to ag applications and medical and health applications.
Can you recall any memorable moments from the past 25 meetings?
One memory that everybody always talks about is Jonathan Rothberg [in 2010]. He carried [the Ion Torrent sequencer] down the aisle, it was like a wedding. People were always coming out with new technology at the meeting. By the way, there's so much gossip, there's so much drama [at AGBT]. It's actually good-natured drama compared to the drama we're dealing with politically right now. What's happened at the meeting is that everything is sponsored. You know, if you put a Dixie] cup down on somebody's table, somebody's got to pay for it, they'll make a company sponsor it. And sometimes they run out of things to do — every lunch has been sponsored, every dinner has been sponsored. So, one year, Ion Torrent cut a deal with the hotel or the condo next door, where they paid them a bunch of money for them to park this educational bus within walking distance, like two blocks away. And then they put spotlights on it at night, and you could go see the [sequencing] machine over there. I think at night, they would also serve liquor and all this other stuff.
Also, it wasn't that many years ago that the Ultima Genomics machine came out. It was the size of, like, three refrigerators, and everybody was excited.
A big technology reveal used to be the last talk of the meeting, right?
The technology development session was always the most popular. Back then, the meeting would always go until Saturday, but, you know, people sometimes leave early. But if you put technology development to the very last session, then people would stick around, so we put it at the very end.
The other memory I have is, this was true whether the meeting was in Marco Island or in Orlando, some of the big-wig VIPs in these companies, you know, the Jay Flatleys at Illumina, the other big shots at these companies, they would rent these suites, and then they would have after-parties, and apparently, there've been some very rigorous beer pong matches. Considering that most of us are incredible nerds most of the year, to go there and just have any semblance of actually being normal people is somewhat memorable.
Looking at the agenda for this year's meeting, what do you see as the most important themes? Which talks should we be most excited about?
This year's meeting needed to be a commemorative meeting because of the 25th anniversary. We deliberately brought back some people who have been featured in previous meetings. Having David Altshuler as the opening speaker, he grew up with the Broad, and now he's a big shot CEO at a pharmaceutical company, and his perspective on this is going to be just amazing.
Ewan Birney, I don't need to introduce or say much about Ewan, he used to come to all the meetings in the early years. Having Rick Lifton is certainly a highlight. Richard Gibbs, Stephen Kingsmore, Jeff Gordon, David Kingsley, Ed Green, Joe DeRisi. We made a very strong pitch to some of these people that this was an anniversary meeting. I don't think we've had as many extremely well-known people at a typical meeting.
Moving beyond AGBT — five years ago, NHGRI laid out a strategy for advancing human genomics and made these 10 bold predictions for where we would be by 2030. How far along have we gotten?
A lot of folks, especially science writers, tend to index off of our bold predictions, as opposed to the first seven pages of the strategic plan. We got slowed down because of all the things going on in the government right now, but we actually are putting together a resource that will clearly link a bunch of new programs the institute has launched since 2020 that are now in place. Those will be aligned with earlier parts of the strategic vision, not the bold predictions. Our ability to fund grants and get things through the pipeline has also been slowed down, and a little bit paused by the administration change, because otherwise we would be announcing in the next few months some new programs that are brand new that are being funded that are part of the strategic vision. We're doing extremely well on moving forward programmatically at many of the things we described in the strategic vision.
You asked about the bold predictions, and of course I chuckle a little because as we wrote them, we didn't really think most of them were going to truly come true in the short term, they're about long-term destinations. I think we've made progress towards them. One prediction was that a genome sequence would become as routine as a complete blood count. No, it's nowhere near that yet. But is it more commonplace in any setting, is it now part of a diagnostic workup? Yes, absolutely. I don't know if we're going to get there by 2030.
Could your genome be accessible on your smartphone? There's a number of things that are being put into place for having your own genomic information accessible from your smartphone, maybe your most medically actionable information, and I think we're a little closer to that now than we were five years ago.
One of the predictions relates to, "Will we understand genomic variation? Will we be able to readily go from having a genomic variant to predicting what the biological outcome of that is?" I think we've got a long way to go. That's not going to be complete by 2030, but I think there's been tremendous progress made in that area, both at the level of actionability, such as our ClinGen program, but also from a more basic science point of view.
I do think you can look at every one of our 10 predictions, and you would see programs that we put down on the track that are moving us closer. But you know, they were meant to be audacious.
What's been the greatest impact of genomics in medicine in the last five years? In 2018, you said it was rare disease diagnostics and noninvasive prenatal testing (NIPT).
Impact can be measured with various rulers. If it's by the sheer number of tests, it's definitely NIPT still. If it's seismic opportunities, I think the potential around cancer is overwhelming.
I have almost gotten emotional when I have listened to talks by Stephen Kingsmore. When he tells some of these stories of newborns, where they really were convinced this newborn was going to die, and they did a rapid genome sequence, and they saved that child's life, it's like "genomics saves lives," whether it's one life, or 10, or 20. I'm not saying it's saving hundreds of thousands of lives that way. If you would have told me when I got involved in the Genome Project in 1990 that in my lifetime it would be saving lives, I would have thought that was some future generational thing.
How do you measure impact? I think if you save one person's life, that's everything for that one person. There's so much activity in that space, state by state, a lot of states are moving forward with making it mandatory that these major neonatal intensive care units must have rapid genome sequencing capabilities. And to have it mandated at the state level is pretty remarkable. Then you look around internationally, this is also going on. It's hard to change medicine, and this is absolutely changing medical practice.
Have there been things that have captured my attention that I am keeping an eye on more than others? It's the number of studies and the amount of scientific attention being now paid to sequencing the genomes of healthy newborns, not just here in the US but around the world. When I first became [NHGRI] director 15 years ago, we stimulated that area through a program called NSIGHT (Newborn Sequencing in Genomic Medicine and Public Health). That's actually what funded Kingsmore's work. He was at the University of Missouri-Kansas City School of Medicine at the time, and he got the only grant for sequencing acutely ill newborns.
And then there were other studies as part of NSIGHT about healthy newborns. Our studies mostly revealed that it's sort of helpful, but it didn't move the needle all a lot. Now, not by anything we did, the needle seems to be moving, or at least a lot of attention is being paid, in a lot of other countries, and there is a lot more literature. I've talked about this since the beginning of genomics. One day, we will sequence every genome. I'm beginning to see some movement, some attention around the idea of systematic sequencing at birth. I'm not saying it's going to happen, and I know there's a lot of barriers, there are a lot of issues around cost, privacy. Last year, I spoke at the ICoNS [International Consortium on Newborn Sequencing] meeting, which Robert Green and others have organized. Just sitting in the audience, and different countries coming up and describing their large studies of newborns, it just captured my attention; I really find myself fascinated by this. I don't know if NHGRI is going to put an oar in the water. We're in a weird budgetary time, a lot is going on politically, we'll see what happens. But it is just something I'm watching.
The new Trump administration has taken a number of steps to reduce federal spending, including cutting the size of federal agencies. How have these measures affected NHGRI so far?
We really don't know. The reason I call it an administration transition is because everything's transitional. Things just have to slow down a little. And this has happened before. I've been through multiple administration changes. I came in under Clinton, but then I went to Bush, Obama, and then Trump, Biden, and Trump again. I've seen these transitions take place. I've been in the government 31 years, half the time as a director. So, half the time I was dealing with this at a micro level. The other half, it affected me, but maybe not at an hour-by-hour basis. The transition is the transition. And hopefully, we'll start finding everything will go back to normal, and then there will be lots of issues around budget and many other things.
We only got a new secretary [of health and human services] a few days ago, and we don't have an NIH director yet. So, a lot of things are transitional until you get all the leadership in place. We have a new secretary who is passionate about a number of things, and one of them is chronic disease, which is a beautiful, complicated example of genomics and the physical and social environment. We're excited at the idea that genomics is poised to make major contributions, as we've been working on ever since the end of the Genome Project, to define the genomic basis of common and chronic diseases. And the field of genomics will work hand in hand with experts who think about the social and physical environment, and social determinants of disease and health, and how those interplay with genomics. We stand ready to be able to tell our stories of how we believe genomics can make contributions to priorities of the new administration.
Have any grant funding decisions been delayed because of the transition? I noticed, for example, that the National Advisory Council did not meet in February. Is it going to meet in May?
We're waiting for all of these things to begin to move forward. It's not unique to our institute. The whole federal advisory committee scheduling infrastructure, all that has been paused, and it will then be relaunched.
The new administration is de-emphasizing certain areas and programs. How has that already affected NHGRI programs, for example, the Action Agenda for Genomics Workforce Diversity?
We are obviously looking at all of these things, we're looking at the executive orders, we're excited to now have a secretary in place, we want to be able to get the deputy secretaries and then deal much more closely with our administration. We have lots of questions. We want to make sure that we stay in alignment. All this is happening fast and furious. We don't know what the specifics are going to be, and we're prepared to have discussions to figure it out.
If the proposed cuts to indirect costs paid for by NIH grants go through, how do you think this will affect genomic research?
I don't think it's going to be unique to genomics. I have no idea. This is a very complicated ecosystem of biomedical science, based in academia, based in the private sector, based in not-for-profits, and then with government funding. And if dials are going to start to be changed, then it's going to affect everything. I am not an expert in all the economics of this, and there's a lot being written about it by people who know far more than I, so we'll have to see.