The Bioinformatics CRO Podcast

Transcript of Episode 84: Eric Green 

Disclaimer: Transcripts are automated and may contain errors.

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Grant Belgard: Today on the Bioinformatics CRO Podcast, I’m joined by Dr. Eric Green, chief Medical Officer at Illumina. Eric has spent decades at the center of Modern Genomics with a career that spans the Human Genome Project more than three decades at NHGRI and 15 years leading that institute. As director at Illumina, he now helps guide global efforts around clinical genomics, access to precision medicine, and the diversity of genomic data.

Grant Belgard: We’re going to talk about what he’s doing in this chapter, how his path unfolded, and what advice he has for people building at the intersection of biology, computation, and medicine. Eric, welcome.

Eric Green: Thanks. It’s great to be here and it’s wonderful to talk to you again.

Grant Belgard: We’re very excited to have you. So how would you describe what you’re doing now, both day to day and at a high level?

Eric Green: Let’s start at a high level. To say that I’m only completing my third month here as not only as Illumina’s Chief Medical Officer, but it’s only my third month working in the private sector. I have a long career. First started in academia and then, nearly 32 years in the government. Now only three months in, in not only the private sector, but then at, specifically at Illumina. At a high level Illumina is absolutely at the forefront of efforts to try to see genomics have maximal positive impact on the practice of medicine. Something fundamental to how I got in genomics in the first place and certainly a centerpiece of my efforts while at the National Human Genome Research Institute, in particular when I was the director for 15 years.

Eric Green: And so when they approached me, which really wasn’t that many months ago, after I retired from federal service a year ago listening to their ideas about how they wanna morph themselves from being a very technology oriented company to being a solutions application oriented company, and particularly in the arena of genomic medicine implementation, was like music to my ears. And and so at a very high level I now get to the honor of serving as a chief medical officer of what I think is the premier genomics company that really offers the greatest promise. To really push the envelope by bringing their technology, their expertise into an arena that is primed and ripe and ready to see genomics truly make an impact on patient’s life and improve human health. that’s, that is a very high level statement.

Eric Green: I will also tell you, which is what, the day-to-day part is more difficult, is the other really wonderful part of this job is um, I’m gonna craft it. Illumina has had Chief Medical Officers in the past, but they were at different times. It was, you know, you know, a while ago was their first, and then the last one that was here, hasn’t been here for three years.

Eric Green: And it’s just a different moment in time for so many reasons. And so one of the other great things about this opportunity is really being given a big block of wet, clay, that I’ve now started to mold it to see what the things are that I think we should immediately be working on.

Eric Green: But I am quite certain. Even six months from now when maybe I have a better day to day understanding of what I do, I bet you two years from now, it’ll even be different than that. Because I, I think there’s a very fast dy, fast changing, very dynamic area and to, to, to some extent. I may have ideas, but the more I learn about Illumina, I might even change my approach to what I suggest that they do or how I help them formulate their strategic priorities in terms of genomic medicine implementation.

Grant Belgard: What does the field look like from your seat right now that most people don’t see from theirs?

Eric Green: If I can tell you that 16 years ago, which is I think about the time that I became the director of NHGRI, and the big push I made as becoming the new director was that I thought, and this was around 2010, that I thought the time was right to get serious about investing in research to guide the way on how genomics is gonna be used in the practice of medicine. And we did this in a fashion where we weren’t being overly scripted and saying, all right, first we’re gonna integrate it here and then we’re gonna integrate it there, but rather we, you know, let a bunch of flowers bloom. And invest where you can in terms of research dollars from the NIH and see what happens.

Eric Green: But there was a lot of skepticism. If you go back 16 years, I can tell you that not everybody thought the time was right. The big difference now versus then is that, we proved that absolutely the time was right and starting, eight years ago, five years, depending what area you’re talking about, nobody questions the fact now that cancer genomics is real. That the use of genomics as part of cancer diagnostics, as part of cancer, therapeutic development, et cetera it’s just, it’s absolutely gonna be more and more mainstream. It’s still early days, but nobody questions. It’s gonna be real.

Eric Green: Nobody questions anymore. The idea that genomics is now a frontline diagnostic tool in helping patients who have rare genetic diseases. It’s just routine and in fact, it’s finding more and more, niche uses in that area, including in acutely ill settings such as intensive care units where especially in the neonatal period and even the pediatric period, there’s even some evidence that might be relevant in the adult ICU setting.

Eric Green: Where, patients have come in with undiagnosed rare diseases. If you could rapidly sequence their genome, you can change their medical management. This, nobody’s, nobody would’ve been convinced that was gonna be the case 15 years ago. That’s absolutely mainstream now. Or take an area like prenatal genetic testing. Where now non-invasive methods are used millions and millions of times for pregnant individuals around the world. And these tests are not very expensive. They’re increasingly being covered by insurance and it’s now mainstream that you offer to pregnant individuals non-invasive genetic testing using very powerful new technologies, some developed and refined by Illumina and others that have built on those same kind of technologies and adapted them in other ways. So these are just the early examples. But there’s more coming and there’s a lot of excitement around pharmacogenomics.

Eric Green: There’s a lot of excitement. Even around prevention and thinking about more and more that we can learn things and maybe we learn it earlier and earlier in life, that may help how patients are medically managed, which is why what I’ve gotten very excited about over the last two to three years is the seriousness that many countries are taking in studying the idea of sequencing the genomes of all newborns. To expand upon the well established genetic screening that goes on in most countries for some modest number of rare genetic diseases. And building on that to say, wow, why are we limiting ourselves to just, a handful of diseases? Why don’t we just get comprehensive genomic blueprint information that we could learn a, we can action around and even more than what we’re currently doing.

Eric Green: And yet we know that in the coming decades we’ll even figure out more and more ways to make these things actionable. And so there’s lots of studies multiple ones in the US and dozens around the world.

Grant Belgard: So you gave several examples of incredible applications of genomics that are being rolled out at scale now. What are some areas of genomics that have stayed stubbornly hard. Where maybe they, they didn’t meet people’s expectations from some years ago.

Eric Green: The most obvious area to go to stubbornly well, there’s two kinds of stubbornly hard actually. I mean, maybe that’s the first thing we should do is if you say, what are the stubbornly hard barriers to genomic medicine implementation? I would immediately bifurcate and tell you two different bins.

Eric Green: One is biological and medical complexity, and two is society and the complexities of healthcare. I think we always should be separating those. Not that one is easy and one is hard. It is just that we should recognize some of this is because biology is really complicated and physiology and pathophysiology is really complicated and unraveling that, yes, technically we can generate immense amounts of data and about things that hopefully will one day give us biological insights about it.

Eric Green: But getting those insights is still hard and then we need to separate that from health, healthcare is just so complicated in every country in the world. And we are now in a circumstance where we are trying to bring a significant change to healthcare by, in the use of genomic information.

Eric Green: And we’re running into all of the usual challenges that come with any change in healthcare. So let’s, we, if you want, we can talk about both separately, but let me focus on the biological complexities. The fact is if I, if we go back 23 years when the Human Genome project ended. We, we knew we had a challenge ahead of us in terms of actually interpreting the 3 billion letters roughly, that we had ordered. And we knew it was gonna take probably multiple generations to fully interpret it. But I think a lot of the thought at the, at that time was, all right, we’ll get this inventory of the many tens of thousands of genes we have.

Eric Green: And then when we sequence this and lots of people we’ll find lots of mutations in the genes that’ll tell us a lot about human disease. And, what’s transpired in the last 23 years? First of all, we learned that we only have 20,000 genes. Not that many more than worms and flies. So human complexity does not come in our gene count. And then we learn that holy cow, there’s all this non-coding DNA. which ha is many cases, in many areas, incredibly conserved through evolution, which was immediately signaling to us. That means it’s biologically important. ’cause otherwise evolution would’ve gotten rid of it. And it’s in, in a, the part of the genome that we don’t have the knowledge of the language.

Eric Green: We, we don’t really know how to read out, like the way we can read out the code on table to understand the coding parts of the genome. And then the more we keep studying these things, we also realize, wait a second, there’s an awful lot of reasons to believe that genomic variants are living out in these non-coding regions. That, and that these are the genomic variants that when we do these fancy human genetic studies are the ones that seem to be statistically associated with some of the most common diseases that we need to completely tackle and understand and eventually be able to make predictions about, make better treatments for, diabetes and hypertension and cardiovascular disease and so forth. And one, the, one of the big challenges that remain is learning. About the biology and the medical consequences of variation that exists outside of coding regions.

Eric Green: And there’s every reason to believe that there’s an immense amount of medically important, hopefully medically actionable variation out there.

Eric Green: But we’ve gotta define it. We’ve gotta understand it. We’ve gotta mechanistically characterize it, and that’s really hard. And we’re getting better at it. There’s lots of exciting things that are being done. And yeah, at some point you may wanna ask me about AI ’cause it seems that everybody will always ask the questions about no matter what the topic and in the world is these days, you always say, how is AI gonna influence it?

Eric Green: And of course, I do think AI is gonna have a considerable influence on helping our human brains understand all the intricacies of genome function and, and once again, I wanna stress that over the last 23 years since the genome project ended , as we realize that our complexity, a lot of it lies outside of our coding regions. Thank goodness we’ve had brilliant scientists discover all the different ways that RNA is biologically important and all the different subtypes of RNA and all the craziness of, we’re learning more and more about RNA modification we already knew about RNA splicing and alternate splice forms, et cetera, et cetera. Oh, and of course then there’s epigenomics and thank goodness that the technologies for sequencing DNA have become increasingly adaptable to study epigenomic modifications and. There we go. There we are.

Eric Green: So, you know, all these technologies are just lining up really nice. Oh, and the other variable, of course if we’re sort of saying what are the big barriers, is our, I know know what I learned in medical school. I, I learned about the kidney and I, yeah, I learned about sub parts of the kidney. But the fact of the matter is, even the sub components of the kidney, we label ’em with one name, but of course they have multiple cells within it, and not every one of those cells is behaving the same. And so there’s just a lot of biology at the single cell level. And fortunately we’re getting technologies to be able to study, all these complicated things about omics as we would often say, and doing it at a single cell level. There’s a lot of great science to be done and I and I will say, and maybe this is an important point to, to really make, is.

Eric Green: I do think sometimes when people talk about precision medicine and genomic medicine and multi omics of human health I think sometimes people think because, and they hear it from people like me and others who are very excited about it and we love to point out the home runs ’cause we love to demonstrate that, wow, this really can change clinical management. But I think occasionally people might, and especially younger people, trainees might get the impression that everything proximal to that has been solved. You know that, oh, now all the emphasis is on patient care and patient implementation. And I, every once in a while, just like to fully admit that everything we are doing that has gotten us there is cream skimming. We are, we’re just skimming the cream to be able to show how we can impact patient care.

Eric Green: But left behind in the wake is still the vast majority of fundamental biological knowledge that we need the next generation to pick up the mantle. Some that are gonna be doing overwhelmingly basic research that you know will be a bazillion miles away from clinical care.

Eric Green: And that’s okay. We need them because there’s every little step along the way that we have left unanswered questions. And one, one of the messages I would always like to give and I even think it applies to people doing bioinformatics data science, AI, is, you could say that’s what I’m doing, but you could apply that at the most fundamental level of how a genome works or how genomic variation influences genome function. Or you could use a, [?] to really help implement genomic medicine. But that full spectrum of activities will continue, I’m sure, for decades to come. And anybody who wants to get into that should feel very comfortable to know that there will be opportunities across that entire spectrum that doors are not getting shut.

Eric Green: We are just simply, just trying to open as many as we can and there’s so much more knowledge to be captured.

Grant Belgard: Where do you see the biggest gap between what genomics can do today and what the healthcare system’s able to absorb?

Eric Green: Yeah, so that’s a, it is a, it’s a great question. And you, the answer is there’s just lists and lists of reasons. What I’m learning and maybe even learning a little bit more in the most recent three months at a company that is global compared to my previous 31 years in a federal government that mostly focused on the US.

Eric Green: We, there’s a lot of interest in NIH about how healthcare is delivered worldwide, just getting my head around US healthcare was complicated enough. I, but whereas Illumina thinks more globally, there, there’s just, every possible complexity that you bump up against. And it’s different at every country, but one of the things I would like to point out, ’cause sometimes people say, ah, genomics, just, it’s so disappointing is you’re just not getting that clinical uptake. There is all this promise. I think, again, part of the problem is. Is you’ve gotta take a step back and just fully appreciate how new and how young all of this is.

Eric Green: And one of the points I always like to make is the word genomics didn’t even exist until 1987, which is the year I graduated medical school, and I say that because most of my medical school classmates are still practicing medicine and I got news for you. They never heard the word genomics once in medical school, ’cause the word didn’t exist. Okay? So you gotta feel a little– now, now I’ve gone off and become a genomics expert; they’ve been busy, treating patients and taking– and all of a sudden we thrust onto them all this new abilities in genomics. And, practicing medicine is really hard and they’ve got a lot of stresses and strains. They’re constantly fighting with insurance companies. They’re constantly dealing with a lot of regulatory issues and constantly dealing with a lot of hard problems. Then all of a sudden you throw this genomics thing.

Eric Green: I mean, we haven’t quite gotten to a point where this can be push button for them, and I’m very sympathetic, but why are we there? We’re, there, we’re victims of our own success. If genomics would just slow down for a while, then we’d have time to train the next generation.

Eric Green: But we’ve been so successful that we’ve now thrust upon the current medical system, a whole new set of things where they’ve never had any formal training. And oh, and meanwhile I would also, they’re also encountering, patients who either don’t understand anything about genomics; they, you have patients who actually know quite a bit because they’ve had time to to chat GPT it or to Google it. So sometimes, and I hear this from some of my medical classmates who I talk to they walk into a patient’s room. The patient’s already had their genome sequenced, they’ve already had all these entire, they’ve had time to do it. And the, my poor classmate never had any training on how to deal with the data, the patient’s way ahead of them. So we’re, we have a little bit of catch up to do.

Eric Green: It’s, some of the things I’m gonna be thinking about as Chief Medical Officer here is what do we do to think about genomic literacy enhancement for patients, for healthcare professionals? It’s, and it’s not just physicians. We gotta think about pharmacists and think about pharmacogenomics becoming so important. I think pharmacists can really be helpful here. Nurses, physician’s assistants, genetic counselors, so on and so forth. I think there’s that. I, then, the other example I would give is and this is where I think it’s both, it’s both a challenge now, but it’s also gonna be part of the solution is you don’t have to go– well, well, let’s just go back to the genome project completion 23 years ago.

Eric Green: 23 years ago, there were not really electronic medical records, at least not in the United States. Okay. And now everything is going to an electronic medical record. Now all of this, a lot the way medicine is practiced is interfacing with electronic health record systems but we have not been able to yet have seamless integration between genomic testing, genomic analysis and then get it all fed into an elect, electronic medical records and have it then be with immediate recommendations and all these things called clinical support tools and so on and so forth. Now, the, so the challenge is that we haven’t gotten us all together ’cause it’s all happening so fast.

Eric Green: But the good news is, is actually, these are all sort of made for one another. Genomic information is digital information. More and more medical information is digital information. More and more physicians rely on clinical decision support with popups and assist and blah, blah, blah. And so when we get to the point where we can get all this design correctly and if only we had time to build the airplane and then fly it, but we don’t because we gotta build it while we’re still practicing medicine. We’ll eventually get to that point. But what it does require is oftentimes health systems investing. The infrastructure to get the genomic information, to get it integrated in the health records, et cetera, et cetera.

Eric Green: And it’s not necessarily gonna generate money, generate revenue. It’s gonna be, you gotta make the investment in the short term to get the long term return. And some health systems are surging ahead and they believe it and some are not. And there, there’s just a lot of challenges associated with that.

Eric Green: And then, meanwhile you gotta deal the whole issue about reimbursement, who’s paying for this, et cetera, et cetera. So again, what is more complicated in society than healthcare. And yet what we’re trying to do is really change healthcare. We are, it’s not surprising that we’re seeing a lot of challenges come up.

Grant Belgard: What does good judgment look like in a field that’s moving this fast?

Eric Green: It depends who you ask. And and it depends where you sit, right? And it is it is interesting. And it even speaks to issues about, how when you have, nothing’s unlimited and certainly not, healthcare dollars are not unlimited. There’s lots of decisions that get made all the time of how do you distribute resources across an area and I, and the thing about genomics is that that there’s a lot of immediate utility, but there’s a lot more long-term promise. That, those of us like me really believe in this, but we know it’s gonna be a lot of work and we don’t know exactly the time. And so then what does good judgment look like?

Eric Green: People who are running health systems, people who are making these decisions are gonna have to make actuarial decisions about what problems they’re trying to solve that are here and now problems versus. As the famous Gretzky quote, skating to where the puck is gonna be, making the investment because you truly believe that you’re gonna be in a different place, that if a little bit of financial pain now will put you in a better position down the road and different, I can tell you different countries are tackling this differently for the same reason.

Eric Green: The different countries have different approaches to how they feel the government’s responsibility is with respect to providing healthcare to their citizens. Um, United States is not leading in genomic medicine implementation. That’s just a clear fact. And a few other countries are the, the UK in particular. When I was at the National Institutes of Health, I really, we were watching and interacting and really admiring what some other countries were doing, in part because they were experiments, right? All of us are a heart of, I’m a physician scientist. I’m an experimentalist. it was interesting to watch what other countries are doing. Now at Illumina I have a slightly different set of responsibilities.

Eric Green: And because we’re global, I mean we’re partnering with some of these other countries and their health systems and trying to figure out how we could be helpful and how can we collaborate and how can we facilitate the work they wanna do.

Eric Green: Because long-term goal is to facilitate genomic medicine and precision medicine implementation worldwide.

Grant Belgard: What first pulled you into this field?

Eric Green: That’s a great question.

Eric Green: So, So my story in the field of genomics, my story is a little bit of luck, a little bit of nascent insight and, I grew up in a science family, so it wasn’t totally shocking. My father was a scientist. It wasn’t shocking that I gravitated towards a science undergraduate degree. I watched my older brother decide to get an MD and a PhD to become a physician scientist, and that seemed like a good decision. And I, it felt right to me. I really liked the idea. I knew I always wanted to do science and research. I like the idea of combining it with becoming a physician. But up until the point that I graduated with a MD PhD, I was always– I got a PhD in cell biology. I could barely spell DNA when I graduated medical school and graduate school. ’cause I had done my PhD in studying sugar molecules attached to proteins, these things, glycoproteins.

Eric Green: I was very interested how cells try to sort their proteins within to go to different places within the cell to, to kick them out of the cell. And I really hadn’t thought much about molecular biology or DNA science, et cetera, et cetera. then I decided to train in clinical pathology ’cause it was a very light clinical training. ’cause I wanted to get back to the lab as soon as possible. And at the time there was some in my first, my internship year before I then became a postdoc and back in a research lab. There were some early things that were called Molecular Diagnostic Labs where they were just starting to look at DNA rearrangements in cancer by, by, by technologies that we almost laugh at now. But I thought that seemed interesting. And then again, remember when I graduated, the word genomics was coined.

Eric Green: There was a lot of discussion about this thing called the Human Genome Project. And my circumstance, that I stayed at Washington University where I’d gotten my MD/PhD for residency ’cause my wife was a medical student. And just so happened that Washington University had some of the leading founding folks in the field of genomics who were just leaders immediately and really helped catapult the field forward. And so I got to pick a postdoc mentor and I looked around, I said, I haven’t done anything in molecular biology or DNA science at all. And there’s talk about genomics and there’s these great people here. And I went to talk to one of them. And the rest is history. ’cause I just said, wow, this just seems incredible. They were talking about maybe a human genome project starting and they would be really poised to maybe participate. And so I said I should just build up my tool belt.

Eric Green: I knew biochemistry, I knew you know a lot about glyco biology, I knew about cell biology.

Eric Green: I said, oh, I should probably learn a little bit cutting edge work in DNA science or this thing called genomics. So that was, it was a naive idea. And then when I got into the lab, they started a year later talking about applying for becoming a center for the Human Genome project.

Eric Green: It just felt right. My project was right in line with what they needed to do in the Human Genome project. I just said I got all in, I just got completely mesmerized by this. I found myself suddenly working on the Human Genome Project on day one. I was a postdoc. I’m hiring technicians. Washington University was wonderful to me.

Eric Green: They said “You should just run this ’cause you’re, this is great. This is what, you could build your career in it.” And off I went. I had a vague idea if you took me back in time to 1988, when I made the decision what I was gonna do as a postdoc. I had a vague idea that you could connect the idea of having, if we really sequence the human genome, maybe the way we practice diagnostic medicine or clinical pathology, which was my, my clinical specialty, I could imagine some generation, two, three generations from now. Maybe you would have genomics become part of standard diagnostic medicine, but I couldn’t possibly have defined the timeline or the specific steps to get there. And maybe that’s the most gratifying thing of all is that, then I got involved in the Genome project, got recruited to join the NIH at the National Human Genome Research Institute.

Eric Green: Still never, you know, even when you go back 23 years ago, when we finished sequencing the first human genome by the Human Genome Project, it cost a billion dollars. This was still not in the realm of a clinical test that I, as a trained clinical pathologist, knew. But, but you know, we called for the need at that time for reducing the cost of sequencing DNA as a key thing to follow the Human Genome Project. Um, I was the one that helped craft a sentence in a strategic vision that NHGRI out that talked about how we needed to get it down below a thousand dollars. ’cause I knew a thousand dollars was a good cutoff for a clinical test. that sounded great at the time, 23 years ago, I said, wow, I can’t wait till my grandchildren realize that.

Eric Green: I never thought it would happen on my lifetime, my professional lifetime, let alone on my watch as NHGRI director. But all those things happen. So, And even now, I’m just continually surprised, which is how fast things move. Such that, the fact that I am now existing at a, as a CMO at a company that truly is going to help make genomic medicine a reality worldwide is pretty, pretty remarkable.

Eric Green: And I could I can’t take full credit for having the vision, back in 1988 or whenever that, what this was gonna lead to. But I could see the general direction, but I just feel incredibly lucky that it’s all happening in, in my professional lifetime.

Grant Belgard: What other choices changed your trajectory the most?

Eric Green: I think what other choices, if, when you think about it some choices were, mine and some choices weren’t always mine. One of the, the things I always like to tell young people is. By the way, you don’t ever look at more senior people and think they had a life plan where everything was laid out and don’t even think that they even were in control of all their decisions because a lot of things develop and things. Some of it’s just luck and some of it’s personal, right? It could be, what you have to do as part of your family in terms of when you can move, when you could not move. But I never saw myself, I never saw myself going into the government. I just it wasn’t something that occurred to me. And then one set of circumstance, you know, I thought I was gonna be an academician. I thought I’d be at a university forever.

Eric Green: And I I was an assistant professor at Washington University in 1990, starting in 1992. But nobody ever saw it coming that, that Jim Watson, who was the first director of the Genome Institute and launched the Human Genome Project, that he would end up departing NIH unexpectedly, leaving the Human Genome Project without a leader. All of a sudden, Francis Collins gets recruited to take over the Genome Institute and he says, I’m only gonna do it if we can create a government based genomics program called the, it’s called the intramural program. All of a sudden they say, yeah, you should do that. And Francis immediately tried to recruit a bunch of top flight genomics researchers and genetics research.

Eric Green: He called me up and all of a sudden in one phone call, I completely changed the trajectory of my life. I went from academia and jumped into the government having no idea what I was getting into, but it was, it turned out to be a wonderful opportunity. And within two years I was taking on leadership roles.

Eric Green: I took several, I was able to start a sequencing center and then I was even able to become the director of the institute and then things changed for me. A year ago I retired and and I was I retired from federal service ’cause I was retirement eligible after 31 years. even then, I didn’t know exactly what I was gonna do and I, but I was given a new chapter to explore it.

Eric Green: I, my immediate gut said, go back to academia. And I tried to do some of that. I explored some options. I did some consulting. I also started talking to some other organizations for consulting and and I, all of a sudden was approached by Illumina and it’s it really was almost like instantly, oh my God, this just makes complete sense. And and part of it is, I, it wouldn’t have been just that way for any company. I think it was I’m immensely proud of my time of at NHGRI, and I always say it’s like the icon of genomic funders. It is. It is the top flight one. And I feel the same way about, I’ve always felt the same way about Illumina. They are the icon of genomics companies. It’s, to me, the top one. So all of a sudden when they called me and said, chief Medical Officer and the way it was gonna be formulated was just perfect for me and my family. It was a really easy decision.

Eric Green: I just never saw, yeah, I never saw it coming. And if actually, if. And I had been out looking at jobs and really thinking through what do I wanna do? Where do I wanna, how do I wanna do it? And it just, it hadn’t occurred to me. And although I, to, to some extent it, I was very involved in talking to lots of people and it started through a set of conversations I had, including with the person that eventually became my boss here and the CEO.

Eric Green: So I was open to lots of conversations. I just didn’t see it all falling together until all of a sudden it just did.

Grant Belgard: It’s I’m guessing you’ll have to reach far back for this, but when in your career did you first start to think well beyond individual projects, towards bigger systems?

Eric Green: Yeah, I think implicit in your question is just taking a very big picture view. Of and of scientific challenges. And in some ways it, that was part of what I found very appealing about the Genome project. And if I think about my my graduate work, that was very traditional. Although even then most people have one PhD mentor. I had two. I know. I just immediately saw the opportunity to cobble together that and I also would say that even then, I really enjoyed collaborating with people, some graduate students, some PIs.

Eric Green: I just like working themselves, do my project. I was always very collaborative. Then there was, the Genome project was all about being collaborative and all about being selfless and not worrying about, you really were part of this massive enterprise of thousands of scientists around the world. And really wanna point out for, especially people don’t realize that now we just take that for granted that you know now, you look across biomedical research around the world and there’s still some individual labs, lots of them and individual projects, but consortium science is very accepted. Papers with hundreds of authors, very conventional, you know, now we see that all the time, but back then it was almost frowned upon. Or certainly some people just were uncomfortable with it.

Eric Green: I can certainly tell you that even when I went out looking for jobs in 1991, when I became, you know, not all universities were so, you know, they, I literally applied and got interviewed by some universities in 1991 and they were really interested in having somebody who had some genomics expertise.

Eric Green: It was still a very young discipline. And you’d go there and they’d say what are you gonna work on? And I’d say, oh, I’m gonna keep working on the Human Genome Project. And they said, oh, that’s like really cute that you’re working on the Genome project, you’re not gonna build a career on that.

Eric Green: What are you really gonna do when you grow up? And it’s like, no, no, I’m really gonna do this. And it quickly became apparent that was not a university I wanted to go to. I will say over the years, universities have had to decide whether or not they’re comfortable having their investigators be part of these big consortium, because the genome project was the first of many just in genomics.

Eric Green: But now we’ve seen it in neuroscience, we’ve seen it in microbiology. We see it all over. For some science consortium based work is the way to go. And especially as science gets more complicated and more technical, you need a dream team of interdisciplinary experts and you gotta, you, it’s like a Noah’s ark kind of a thing.

Eric Green: You need to have two people that really know genome sequencing. Two people that really know AI, two people that really know biochemistry, two people that really know physiology. This is how you move big things forward. My thinking about what I what, and it’s not for everybody, but it’s, it meets my personality extremely well. I had, I’ve been thrilled and fortunate to be able to be part of consortium as the Genome Project and things like Encode and some other programs like that. But then in 15 years as NHGRI, director and NHGRI is the poster child of running a consortium. We ran a bunch and we even did some that were NIH wide, even beyond our own institute because NHGRI showed tremendous leadership for NIH Common Front efforts like. Human Microbiome Project, like the human heredity in health in Africa, H three Africa program.

Eric Green: that’s, that’s, this is our expertise for many years and still is. NHGRI really is the leader in how to run consortium based science.

Grant Belgard: What did you underestimate about leadership earlier in your career?

Eric Green: What did I under I think I would say what I underestimated about leadership early in my career, which I always chuckle about, is that, you just had no formal training in what you were being asked to do. You know, and whether that leadership is just running your lab or running a small, like a branch or a department or running a center or running, an entire institute is, all of that.

Eric Green: When you really think about even just running your own lab, it’s like running a small business, right? You have to deal with bringing money in. You gotta balance your budget. You gotta, you have personnel issues. You have, those can get complicated. You gotta hire, you gotta fire, you gotta discipline, you gotta encourage, you gotta mentor, as you’re not really taught much of that.

Eric Green: And sometimes you and then as you take on more and more leadership roles, the res roles and responsibilities get bigger and harder. I will tell you, when you’re at the top of an organization like the yuckier the problem, it’s gonna go to the top. So all of a sudden you’re dealing with things you just can’t even imagine you ever had to deal with. You just don’t realize it until you’re there and you real. But on the other hand, what makes great leaders is I think, and I could talk a lot about leadership. But, two things I think that are absolutely essential is one you’ve gotta just be completely ready to be a lifelong learner of skills.

Eric Green: You just can’t assume that you’re going in and you’re gonna just know what you’re doing. You’re gonna learn it because you have not been taught. But the other key aspect of it is you have to learn how to surround yourself by outstanding people. You have to have the ability to just be very comfortable delegating to them, trusting them, and you have to develop incredibly strong relationships with your immediate folks around you.

Eric Green: ’cause it is a team sport. You run something like an NIH Institute, it is a team sport. And when you’ve got a great team, you’ve got a great institute. And when you, and it’s, you gotta cultivate that team. You gotta pick ’em carefully. You gotta nurture ’em, you gotta mentor ’em. And you gotta let ’em tell you when you’re being wrong and you gotta be humble and be ready to learn and adapt. But it’s it’s critically important. You’re only as good as your, as the team that you surround yourself with.

Grant Belgard: Now for the question you know is coming. What about AI? What are your expectations for the impacts AI will have in the coming years and the new and new challenges it may pose as well.

Eric Green: Yeah it it’s just it’s the same question you could almost ask anybody on the street about society. It’s, you’re just seeing it everywhere and it’s remarkable. Here’s what I, here’s what I would say is it’s almost impossible to even claim your an, for me to claim I’m an expert in this other than I, I can just watch what is happening and it is like everything else it’s just changing in a breathtaking way. Practically measured week by week. You can just see this what I would point out is that not that AI is an incredibly important in all the other ways of everyday life that it’s now finding itself. I, you know, I’ve been saying even before this incredible uptick, so I probably was saying this 5, 6, 7 years ago. Is it’s this humbling nature of, of the genome that I spoke about earlier, that it is just so incredibly complicated.

Eric Green: And the more we dig, the more we realize it’s even more complicated than that. And it’s so humbling. It’s only 3 billion letters and it’s just amazing how much it does to create and operate a human being. And then you realize how incredibly complicated non-coding DNA is, for example, and it’s all a language issue that our, the human brain is just struggling getting our heads around that. It just, this is just seems like the perfect marriage. It just seems like the perfect application is to bring this in to be able to see, generate these massive data sets.

Eric Green: So we’re good at generating the data. We’re just not good at extracting the knowledge from it. It just seems like you know that it’s a match made in heaven. But the other aspect of it is, it’s what I’ve seen in particular in the last 10, 15 years, is that it does attract the best minds. And that’s, that gives me a lot of optimism.

Eric Green: So some of the best computational biology, best AI experts really see this opportunity in biology. And then, and that’s just in the genome. And then of course, if you start to pivot us into sort of the genomic medicine, precision medicine realm, you start layering into that other omic data and other data about ourselves that we capture environmental data, physiology data.

Eric Green: And then you marry that with electronic health records. You know, It’s this big bouillabaise of data that, sounds really great. You wanna integrate. Holy cow. The complexity of that data integration process is we’re we actually, it’s not that we’re gonna benefit from AI. We absolutely, desperately need it.

Eric Green: We’re never gonna get through it without it. It’s like, to remind people that 23 years ago when the genome project ended, I remember we tried, at NHGRI, we tried to convene a workshop. we said, Hey, look at us. We’re really cool. We got 3 billion letters of the human genome finally elucidated. We’ve got a big data issue and I remember we tried to convene a workshop and we invited a whole lot of the, some of the best computational biologists from Harvard, Stanford, yeah princeton all, and we were a little disappointed. A lot of people just weren’t interested. They didn’t wanna come to this workshop.

Eric Green: And normally they would come to NIH workshops and when you would talk to them, they’d say, we’re really big data people, this is climate data, financial data, you, 3 billion, you don’t really have that much data. And it was very humbling ’cause we were drowning in these 3 billion letters. That’s completely changed now. And I think you’ve seen it ’cause the technology uptick, lots of genomic data, a lot of other omic data and obviously electronic health. So now the one thing, unlike 23 years ago now, the best and the brightest come and they wanna work in this area because, ’cause we finally got to the big data stage, even though we thought we were there before.

Eric Green: We weren’t until now or until recently.

Grant Belgard: What advice would you give someone early in a genomics or bioinformatics career?

Eric Green: I would probably have a lot of advice to give them the fir, The first thing I would advise them and ’cause I’m, and is: don’t worry. What I first find about young folks these days, they just worry a lot. And I, and I see this in my own kids just, it’s a generational thing. They just worry.

Eric Green: And yet all I see is opportunities. All I see is in incredible, a spectrum of things to be done that, that are really meaningful, important problems that I am quite hopeful there’ll be great employment opportunities, and I know we hit speed bumps and some years are better than others.

Eric Green: And I know we’re in a rough period now but I really do see this incredible set of opportunities and I hope people don’t get so worried. They say, Ugh, I don’t want to go into life science. I don’t want to go into medicine. I don’t wanna go into biology, so forth. So first thing, and then, but the other thing I would say is and part of what they’re worrying about and it gave, was related to the story I told you earlier is worry that you can’t map this out for the next 20 years. Just what I constantly tell people is pick something that really gets you excited, almost to the point where you can’t sleep in the morning. ’cause you just wanna get back to doing what you were doing. And if you’re not that excited about what you’re doing, find something else to do.

Eric Green: And if you’re, if you wanted to be in the, and I think as much data science and AI and all, those are great tools to pick up, but they’re so applicable in so many different areas. Make sure you’re excited about what you’re working on and if it’s, and if you don’t, and also realize the opportunities are gonna change over time and doors are gonna open that you never could have anticipated. And and just be enthusiastic and excited. And if you’re not enthusiastic, excited, find something else. ’cause at the end of the day, there’s plenty of opportunities and chances are if you have enough curiosity that you wanted to get trained in computational biology or data science, AI and so forth, I’m sure you’re gonna find something you’re gonna get excited about.

Grant Belgard: What skills are rising in importance faster than people realize?

Eric Green: You know, well, one of the I think I’d say is I, one thing I get a little worried about is that the, you know, especially around my younger people is the pandemic was very isolating. now there’s a lot of a lot of abilities to do remote work and to be very isolating professionally. And I think one of the skills, a little and I’m allowed to worry a little. I don’t worry a lot, but I, one of the things worry a little bit about, And maybe if in the terms of advice is, don’t get too comfortable just being isolated and feeling like I’m just, I actually think one of the really important things that are underappreciated interacting in person with people. Maybe not every day, maybe not but just recognizing that human interaction, especially in in, in the pursuit of advances in science or in medicine, that human interactions are really important.

Eric Green: Some of them could be fine virtually, but they can’t all be fine virtually. I just wanna make sure that the mixing bowl of strategizing, discussing, debating, interacting, And and developing a relationship I think is so important. All this, one Of the things, and I, again, I say this all the time, I think a lot of people a lot of people who are not scientists think that, um, science is a very asocial profession. They think, oh, they think of the scientist at the bench just pipetting and thinking great thoughts and writing great papers. science is one of the most social things I know.

Eric Green: And I’ve, and my career throughout has been overwhelmingly benefited by interactions and then at the extreme interactions at the consortium level where, you’re interacting with people all around the world and you’re, and I’m just worried about the recent trend of, the pandemic and isolating and the ability to exist and work virtually and interact virtually may take a little of the momentum away from what I think is one of, beneficial parts of science, which is being a highly social endeavor. I just would caution people about thinking the perfect job is one where they never have to interact with people. ’cause I think that the interaction is really important, including in-person interaction,

Grant Belgard: So on, on that note. What do you find makes a mentor relationship most useful.

Eric Green: The mentor mentee relationship. Most useful. I think it’s, I think it’s one Having the mentee’s interest mind and not let anything be cookie cutter. you know what? I always tell people, I and I mentor lots of people in lots of ways. Even today, I’m still mentoring lots of people. I can tell you on my calendar this week, there’s like two or three meetings I’m having mentoring folks the, you know, who are late in their career, middle of their career, early in their career, gets a life being mentored as a lifelong endeavor. I’m still getting mentored.

Eric Green: I, I got news for you when I became. The, The CMO I’m in a whole new world. I’ve been having conversations with some of my lifelong mentors just ’cause I think bouncing ideas off of them. What, it’s not cookie cutter. And the other thing is the most important thing for a mentor to realize is their goal is not to replicate themself in the mentee and make a mini me, to help guide a person who let them be who they are and even if they’re radically different. In fact, what I always tell people when I give ’em advice is have role models and you should have anti role models. and even your role models, there may be half the things that you wanna emulate in your role model, and half the things absolutely not emulate in your role model. You should pick and choose and feel what’s comfortable for you and pursue that.

Eric Green: So I, I just think there’s sort of an open-mindedness that you can’t, and, and I think if a mentor is way too much about I’m trying to make widgets, and this is the parameters of that widget, that’s just the wrong approach to mentoring as far as I’m concerned.

Grant Belgard: What question do you wish people ask more often?

Eric Green: What question do I wish, you know, you mean like when they’re entering their career?

Grant Belgard: Yeah. Yeah.

Eric Green: Yeah I wish, people would ask, or just be show I I actually, maybe I like it when you question the journey about how you got to where you are. As opposed to, because what I sometimes find that’s humorous is they’re, going through the process, they’re so fixated on asking questions like: take a third semester of calculus? Should I take physical chemistry or not take physical chemistry, especially those who are really trying to get into competitive programs, either medical school or PhD. And I just, I just think some of those are sort of the, the wrong question and I just wish they would ask more people about their journeys so that they realize that everybody’s journey is different and that they shouldn’t try to put themself in a trajectory that is well-defined because there’s no such thing as a single route to get to a destination.

Grant Belgard: And to wrap up what are you most excited to learn next?

Eric Green: To be honest with you, maybe the answer I would give is what I am most excited to learn next is how I can be impactful in a whole new setting, one that is focused on the same goals that I had in the previous three decades. And what I mean by that is, I feel so fortunate by having the career that I had at the National Human Genome Research Institute and I, laser focus, if I had to summarize what we were trying to accomplish, especially me as the director, was, can we make genomics truly improve the practice of medicine? I am now in a completely different role in a completely different part of the ecosystem. And yet I’m, we’re trying to do the same exact thing. And, so what I am most excited about and what I really most wanna learn is what can I do to, to help Illumina in their role in the ecosystem. Truly see genomic medicine and precision medicine become a reality.

Grant Belgard: Eric, thank you so much for joining us.

Grant Belgard: It’s been a pleasure.

Eric Green: Absolutely. It’s been a great conversation and good to see you.