Federal Research: NHGRI
A Genome Unraveled: The Code of American Innovation
In this episode of unNatural Selection, we sit down with Dr. Eric Green, former Director of the National Human Genome Research Institute (NHGRI) and a pioneering force in genomics innovation. Dr. Green reflects on his experience helping to lead the Human Genome Project, discussing how competition between research labs and private companies shaped the project’s outcome.
We also dive into how the government stimulates innovation in genomics, what makes a grant proposal stand out, and how researchers can stay competitive. Our conversation turns to the current federal challenges facing scientific research more broadly—and the profound and unsettling effects of recent funding cuts and lab closures on NHGRI in particular. Dr. Green shares a candid perspective on how these shifts are threatening the U.S.’s leadership in genomics amid intensifying global competition, especially from China.
Tune in for a captivating conversation about the intersection of competition, innovation, and the quest to understand the human genome.
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Doctor Eric Green is a genomics researcher, Human Genome Project participant and former director of the National Human Genome Research Institute, or NHGRI, at the US National Institute of Health.
He was at the Institute for nearly 30 years during which he held multiple key leadership roles.
1:31
For just over 2 decades, Dr. Green directed an independent research program that included integral start to finish roles in the Human Genome Project.
Doctor Green earned his MD and PhD degrees from Washington University in Saint Louis.
He has authored and co-authored over 395 scientific publications and has earned several honors and awards, including election to the National Academy of Medicine in 2023.
1:55
Doctor Green, it's a pleasure to have you here.
1:58
Speaker 1
Well, Nick, thanks for inviting me.
It's a it's a pleasure to join you today.
2:02
Speaker 2
And, and obviously we both spend time at Washington University, which we'll get into in Saint Louis, both of us part of the human genome project.
So I'm, I'm eager to unpack that because I definitely get a lot of questions about that.
But before getting started, the general question I ask everybody just to kind of set context is what business were you in and what was your role within that business the.
2:24
Speaker 1
The use of the word business is not always the one used in for government work, but I get what you mean.
It's basically what's the responsibility that we have at the National Human Genome Research Institute and, and my role in it when I was there for 31 years to to help set a context is probably worth making sure everybody knows what genomics is, since the responsibility of the institute was to lead genomics research in the country and really for the world.
2:52
What is Genome Research?
A genome is all the DNA of an Organism and the study of a genome is the field of genomics.
It's actually a relatively young field.
The word genomics was actually coined in 1987, happened to be the year I graduated medical school.
3:07
And that happened because this new field was growing rather rapidly, because the tools for studying DNA had improved so much throughout the 1980s that the idea of comprehensively studying all of the DNA, the genome of different organisms, sort of seemed to be possible.
3:29
And that led to the launching of a field in 1987 called Genomics.
And it was quickly thereafter led to the launching of this big project, which I know we're going to talk about, called the Human Genome Project.
Now, the National Human Genome Research Institute was originally created by the US Congress in 1989, first as an office, later as a center, eventually got named into an institute and it was created specifically to lead.
3:58
The NIH is the National Institutes of Health.
Efforts in the Human Genome Project and the Genome Project ran from 1990 to 2003, and ever since 2003, I would say the business that that NHTRI, the National Human Genome Research Institute, is in is leading human genomics research both in the United States and around the world.
4:23
Now, you also asked me what I did, and in my 30 years plus years there, I did a number of things.
I came in as a basically an independent investigator working on the Human Genome Project when I got recruited there in 1994.
I'd started working on the project from day one in 1990, but then over the years I, I basically took on various leadership roles that were that I was given.
4:49
And then in 2009 I became the director of the institute.
And I was until March of this year, 2025.
And during that time, what I would say is we expanded the field of human genomics, built on the successes of the Human Genome Project and many, many technical innovations happened along the way.
5:11
But perhaps most important to to stress is that we began to see genomics being used in the practice of medicine, something that is often referred to as genomic medicine, which I think ultimately was the one of the most fundamental goals of why the US Congress, one of the National Institutes of Health involved in the Human Genome Project, was to explore and eventually realize health benefits of genomics.
5:39
Speaker 2
Could you share a bit about your personal journey to genomics?
5:42
The Journey to Genomics
Because when you started this, this was early on, this was a human genome project.
This was before that.
It wasn't as of as an established the field as it is today.
So what led you into this field and and eventually being a part of the Human Genome Project?
5:59
Speaker 1
Yeah, I mean, it's a it's a fortuitous way to get there.
I always say a lot of this is luck and maybe a teeny bit of of ideas of what it might lead to.
As I mentioned, the word genomics didn't get coined.
It didn't exist until 1987, and 1987 was when I graduated with both an MD and APHD.
6:21
So it's not like during Graduate School or medical school I ever heard the word genomics once because the word didn't exist.
But you know, I was a very curious young physician scientist and looking around as I decided first to do training in clinical pathology or laboratory medicine, which is the half of pathology that runs the diagnostic laboratories in the hospital.
6:44
And I will admit that when I was an intern in laboratory medicine, I, I got particularly interested in some of the DNA based testing that was becoming available to patients.
But very, very, very, very simple now we look at it that it's just so much more expansive than what it was then.
7:00
And one of the nice things about doing a pathology residency is you get to do research as part of the residency.
And so by 1988, it came time for me to find a postdoctoral fellowship at Washington University.
And I had really never done any DNA based research, even as a graduate student.
7:16
I was a cell biologist and a biochemist.
And I thought this seemed like a very opportune time to get some skills in this new field of genomics.
So I gravitated to one of the founding fathers of the field and one of the early conceptualizing architects of the Geno project, someone named Maynard Olson.
7:39
I became his postdoc and really the rest is history.
I was afforded the opportunity to be in the right place, the right time.
Washington University got one of the very first centers that was going to be involved in the Human Genome Project.
Maynard Olson put me on the frontline, said you run the project as a postdoc.
7:58
So there I was literally on day one of the Human Genome Project, participating in it, thinking I was going to maybe stay in academia for a long time.
But by 1994, I got recruited to come to the NIH by Francis Collins, who was then the director of of the Institute and to be an active researcher there and then eventually lead all the on campus research that goes on that position called the scientific director.
8:23
And then and eventually when President Obama became the president, he appointed Francis Collins as the NIH director.
And in turn, I competed for and was selected to be the NHDRI director, where I served for about 15 years, a little over 15 years until just a couple of months ago.
8:41
Speaker 2
You mentioned why she was one of the first centers in the Human Genome Project.
And of course all the centers that were a part of this, they all compete with each other.
They, you know, for for grants and for publications and for discoveries and for people.
Yet, you know, the Human Genome Project is often seen as a monumental scientific achievement with a collaborative of all these centers that typically compete.
9:04
The competition between the centers
And so can you share any behind the scenes stories about competition between the centers?
In a second, we'll get into Solera.
I remember that was very clear.
There was a private public.
But if we just focus on the on the public for now, how did the centers relate to each other when fundamentally they kind of competed?
9:26
But now they're all thrust into this project, working together to evolve an initiative that affected all of humanity.
9:33
Speaker 1
What I will tell you is that one of the reasons why the Human genome Project wasn't totally popular among everybody at the time that it was conceptualized and launched was because everybody knew it was going to be unconventional for biomedical research.
I'm not sure everybody appreciates the fact that back in 1990 it was very unusual to have big science, to have big consortium, to have a very highly managed production oriented scientific endeavor.
10:02
And that's exactly what the Human Genome Project was.
Now that's become much more commonplace.
And even since the end of the Genome Project, there's many, many of these examples where consortiums come together, They both have to collaborate and compete at the same time.
But, but in particular what NHRI has demonstrated going back to the Human Genome Project is that there is a way to do this at the NIH and it, it required using funding mechanisms and a style of, of government based funding that is not always used, but it is absolutely in the toolbox available and and it just has to be done in a, in a very specific way.
10:44
So what do I mean by that?
Almost all of the Human Genome Project funding provided by by the NHDRI and similar to other consortium in genomics that have followed are not done by the conventional research grants that NIH funds in bulk, but rather they're done as something called a cooperative agreement.
11:03
And a cooperative agreement is basically what the title sounds like.
It's basically, yes, groups compete to be part of the the consortium, but once they are funded as part of the consortium, it's a cooperative agreement that the government is at the table as equal partners with the scientist constantly, almost on a weekly basis, molding what's happening, shifting money as needed, shifting priorities, changing things.
11:29
It's not about scientists getting money going off and doing things and then reporting back to the government.
The government's on the phone.
Back then it was phone.
Nowadays, of course it would be, you know, some maybe Teams or Zoom or something like that.
But this is done in a highly cooperative way.
Now there there's sociology involved, right?
11:46
So yes, you have these groups coming together that are about every four or five years have to compete with each other to figure out who's going to be part of the consortium and how much of that money do they get.
They also have to cooperate and, and it's never easy and it involves a lot of diplomatic, diplomatic management.
12:07
And that's where the government staff comes in.
You know, in some ways you asked me early on, you know, what's the business that I'm in or what's the business I was in?
What's the business of NHCRII?
Mean they are funding the work, but they're also molding the scientific programs that and they're conceptualizing them often, almost always in collaboration with the scientific community.
12:28
But then they have to manage it because the especially these big audacious programs require a lot of week to week management and a lot of hard decisions.
And that's, that's some serious work.
12:42
Speaker 2
Yeah.
And if we think about Solera, the, the, the biotech company that was kind of raising the public initiative to sequence the genes, the, the big fear there was that they were going to patent the genes and block the research and all of the experimentation would come downstream.
13:03
The Human Genome Project and Solera
And, and I was fairly junior at that was in grad school at the time of the human genome project.
But I remember having this vision of Solara being kind of like the Borg or the, you know, the dark side.
But in retrospect, that race probably stimulated a a sense of urgency on the public side as well, right.
13:23
So can you talk a little bit in hindsight?
Did the rivalry between the Human Genome Project team and Solara help or hinder the progress in getting the project done?
13:33
Speaker 1
It, it, well, first of all, it certainly created a lot of turbulence.
I mean, what I would say is I, I, you know, the human Genome project was trying to figure out exactly how to build that airplane, even though we were already flying it.
And there were multiple ideas that were being tested out and exactly the optimal way to eventually map and sequence the human genome.
13:58
You know, Solera came around with, you know, technology that allowed them to go faster in certain ways and did represent a threat to the very existence of of the Human Genome project.
But also it threatened the fundamental ethos of the genome project, which was to share the data widely, not to commercialize it, not to put up any toll booths and getting access to information about the gene.
14:24
This is humanity's genome.
It should be freely shared.
And that was at the core of what was driving those of us working on the Human Genome project.
You know, that gets threatened and all of a sudden you say, all right, you know, maybe we can't be exploring 3 or 4 different ways of mapping the human genome.
14:40
You know, maybe we now just got a decide on one and just go for broke.
And, you know, there's nothing like a common threat to bring a bunch of, of, of, of scientists who might otherwise be intellectually arguing about a lot of things.
14:56
You bring them together because you realize if we don't all focus and work together, we will be threatened by this alternative model, which is to privatize the human genome, The human genome.
And that just became a galvanizing motivation and ultimately it won the day because we were able to get it done.
15:17
And it was also very clear that only one was only one model going forward for getting a finished human genome sequence, which was very tedious and very expensive.
And that was going to be the human genome project.
Which is why after Solara created their draft sequence of the human genome sequence in parallel with the human genome project, they sort of faded away because there really wasn't much of A business model considering the human genome project was going to provide the human genome sequence for free, open source it.
15:46
And so it did speed things up.
I think most historians and most of us involved realized it.
Did you know the project was originally slated to take 15 years and finished in 13 years, But it it really did galvanized everybody to just start rowing in the same direction did.
16:04
Speaker 2
The leadership at the Human Genome Project use that as a way of motivating the people within the project to work harder.
I just, as you were talking about that, I was reflecting and I remember feeling a sense of urgency, like whatever I need to work on, I need to work on it fast because we have a competitor that's trying to do the same project, but in the wrong way.
16:24
So was that intentional or was that just a byproduct of the competition?
16:28
Speaker 1
Oh, I mean, it was a byproduct.
I mean, I, you know, I don't think anybody, I don't think anybody in the Human Genome project wanted the competition per SE.
But you know, it, it became, it is what it is.
It was what it was.
You had to deal with it.
Solera played it hard.
16:44
I mean, they, they, they played it hard and there's a lot been written about it.
They, they wanted to get the, the human Genome Project to move on to other organisms and to forget the human genome and work on the mouse genome, for example.
And that was just not a tolerable idea.
And so it became absolutely all hands on deck.
17:05
And again, this is where being a cooperative agreement.
Francis Collins was essentially the by the way, this was not just the NIHI mean.
I I should probably make sure everybody realizes this with the human Genome Project was an international effort.
At the end of the day, there were five major groups that were involved.
17:22
There was a series of additional groups, but it was from multiple countries.
But Francis Collins is the director of the NHDRI, sort of the, the, the, the field general, if you will.
But he worked closely with the other funders.
But they were on weekly conference calls.
And the way it was organized and everybody agreed is like, all right, this is what we're going to do.
17:41
And, and, and he on a weekly basis figured out what everybody was producing, whether they were coming up with the, the totals that they said they were, if they weren't, they would shift resources around either money or clones or materials.
And it was, it was, you know, it was all out.
17:57
It was all out at the end.
And then then it requires some diplomacy to make sure that that nobody would lose face.
That's when President Clinton got involved because there was no, it was not a good value to have the government beat up on a company, nor was a good value to have the company make the Human Genome Project look unsuccessful.
18:15
And so at least for the draft sequence, which was not the final one, just the draft one, was this big event at the White House where President Clinton basically declared it a draw.
And so everybody could get credit for getting us where we were, and then the Human Genome Project put it across the finish line a few years later.
18:33
Speaker 2
Yeah, part of the diplomacy you were talking about before, part of the government getting all these centers that typically compete to all work together in this collaborative.
18:41
Speaker 1
Well, that's right there was that.
Well, first of all, I mean, you are right, there's concentric circles of diplomacy.
I mean, one was getting the NIH funded centers to work together because that's exactly the money that NIH can control.
Then you had to get all the different groups funded by different funders.
18:59
I mean, there was a Department of Energy group that was funded.
There was a group in the UK, the Welcome Trust, and then there were even some other groups.
So then you have scientific diplomacy around the world and then you have to have the diplomacy, which is where President Clinton and Tony Blair came in to get Solera and and the Human Genome Project to agree to a sort of a tie for the draft sequence.
19:23
Speaker 2
When you think about that level of coordination, and we talked about the role that NHDRI played, especially underneath the NIH, there is a significant amount of direction that the government plays in stimulating innovation in fields.
19:39
How to stimulate innovation in genomics
And if we think about just genomics, obviously one of the logical ways is through grants.
You put out these grants, you say this is the field of the kind of work that we're interested in, and then people submit for those.
Can you reflect upon your experience a little bit in driving innovation and genomic research, especially in a field that was developing as fast as this, right?
19:59
When you're like at the drawing board, thinking about what grants you're going to put out for that year, for that portion of time, there are so many different directions.
So you can choose to put your money, but there's a limited pool of money.
So how did you choose which direction to stimulate innovative work in genomics?
20:17
Speaker 1
I mean, it's, it is one of the most important things NIH has to do all the time across all the institutes, all the areas of science.
I think there's great stories to tell within genomics because as you point out, genomics has been driven by technical innovation and the role of NHDRI is to stimulate those kinds of technical advances.
20:40
I think let's focus because I think I can illustrate some really important points if we just focus on the sequencing of DNA, because there's two stories I'll tell you.
20:49
The sequencing of DNA
And sequencing DNA is reading out the order of the building blocks of DNA.
And within that order of all those building blocks, the GS, As, TS and CS.
And DNA is encoded all the information necessary for, for, for, for life.
Essentially when the genome project began, nobody ever thought we would sequence the human genome using the then available fundamental method for sequencing DNA.
21:15
Fact, for many years in the genome problem, the first 4-5 years, six years the human genome, there was a lot of attempts to make innovation, better ways of sequencing DNA and, and they said we won't start sequencing the human genome until we have an all new method or methods for sequencing DNA.
21:32
That was the mantra.
Meanwhile, there was a lot of technical innovation to improve on the fundamental method that was available at the time for sequencing DNA.
And there was greater accomplishments in incremental improvements, evolutionary improvements of the existing method that ended up outstripping the development of any new, all new method for DNA sequencing.
21:56
So one of the surprises of the Human Genome Project that's been extensively written about is at the end of the day, the fundamental biochemical method that was available on day one of the genome project was the fundamental method that actually sequenced the human genome for the very first time.
22:11
And that was surprising.
So that's a story of technical innovation where it was incremental that eventually led to like a revolutionary improvement in how we could sequence DNA.
Here's the however which leads to the story #2 because the however was while the Human Genome Project was successful and in April of 2003 declared they had sequenced the human genome for the first time.
22:37
It came at a price tag that was was was money well spent, but it was a billion dollars roughly.
So sequencing that first human genome cost something like a billion dollars.
And the reason why this brings up story #2 is because the day the Human Genome Project ended, NHDRI, in doing its business of leading genomics research, published in the journal Nature, a new vision for genomics research starting with the completion of the Human Genome Project.
23:07
And we said a lot of things.
There was like 20-30 major points we made in that paper.
I was one of the co-authors and but as the pathologist, somebody thinking about diagnostic tests, I was involved in crafting a really important sentence in that paper, which talked about how while we should be very proud of having the first human genome sequence, you know, a billion dollars is a little expensive for a clinical test.
23:29
And I was the one that pointed out, you know, a reasonable diagnostic, you know, a blood test or really good comprehensive diagnostic test of some form really needs to be more like $1000.
And we put into print in this new strategic vision published in 2003, the call for developing all new technologies that would eventually get us to the point where we could sequence the human genome for $1000 or less.
23:54
And that phrase, the $1000 genome became well known and and a battle cry for the entire genomics community.
And I would actually contend that what started in 2003 in terms of new methods for an all new methods for sequencing DNA represents one of the most impressive accomplishments and technical innovation ever supported by the National Institutes of Health.
24:19
There are others, but I can I can tell you this is certainly in the top few because what has transpired is since 2003, we have achieved the ability to sequence a human genome for less than $1000.
That is more than a million fold reduction in the cost of sequencing human DNA or any kind of DNA since the end of the human genome project.
24:41
And you may ask, well, how did you get there?
24:44
How did we get there?
And I would tell you there were two things that were instrumentally important.
One was we weren't the only ones involved.
The private sector got very excited about this and a lot of companies started to develop and they got in the game and they waited for academic advance.
25:00
They did some of their own research, but they also waited for some academic advances that came out of other key factor, which is NHDRI launched a technology development program and it was called the $1000 genome program.
And it was basically an attempt to stimulate all new approaches for sequencing DNA.
25:17
And the way we did it, and I can't take total credit for I wasn't the director back then.
I just got to watch from the 50 yard line had a really good front row seat is that they didn't just tell people go off and and figure out new ways of sequencing DNA.
They put out different kinds of funding competitions, one that would get one that called for, you know, a little improvement in sequencing and and reduction cost.
25:42
Another one that was a little crazier, that would reduce the cost even substantially.
And then they even called for really crazy high risk ideas where they knew that, you know, 90% of them would fail, but just bring us some crazy idea.
And they funded them separately and they didn't let them compete with each other.
25:58
They had different bins so that the groups that were a little more conservative would compete with each other.
Those in the intermediate group would compete with each other and the crazy ideas would compete with each other.
And you know what?
They all bear fruit.
Every one of those categories incrementally gave you something along the way over the multiple years that program was funded, and the rest is history.
26:18
And thank goodness the private sector was there standing by grabbing the advances, grabbing the patents, grab getting royalties and and now as you well know, we have multiple new methods for sequencing DNA.
These are all these called these next generation sequencing methods and and the innovation continues even to today.
26:38
But we achieved the goal of the $1000 genome a number of years ago and it has been transformative across all the life sciences and increasingly in medicine.
Amazing.
26:50
Speaker 2
The way that the federal government can stimulate not only research, but technological development and generation of ideas, right.
You just, you come up with, here's a problem, here's a, a bundle of money, we're willing to pay for it.
And then you just, you throw it out there and you just draw all these, the greatest minds in those fields.
27:10
You just come up with solutions, like you said, the wildest ideas.
We just want to see what crazy ideas are out there, see what works, because you never know which one is going to work or what derivative of that initial attempt might actually work.
And, and when you're thinking at that level, at a very high level of throwing around very large dollars, it's, it's amazing how you guys have effectively shaped the course of genomics.
27:32
And to your point, gotten us here in 22 years to the point that we've gone from a billion dollar genome to sub 1000.
And now people are talking about using it.
Well, they are using it already in clinical levels, obviously in, in specialty care and in other areas.
27:49
But now when we start thinking about it as a screening mechanism at population levels, we're almost there and and it's just been just over 2 decades.
27:59
Speaker 1
And, you know, I also want to stress one thing.
I think sometimes people think like, you know, the government's over here and they're not talking to people and they just throw out ideas.
And I, I can certainly tell you that's the furthest from the truth.
I mean, throughout all this time, NHRI and its staff and its leaders like me, we are constantly talking to the community and we're even talking to the companies.
28:18
I can tell you that as the price of DNA sequencing started coming down and these companies started popping up that had all these new technologies, I would frequently talk to the heads of these companies and I would say, what do you need next?
What do you need that you're not doing in house?
Because they're of course doing, there are their own R&D, but they, and they would, it was such a wonderful collaboration cuz they would say, you know, this is the kind of stuff that is a little too risky for us.
28:43
We'll take it and we'll, we'll commercialize it when it gets to this stage.
But what we really need is some innovation and such and such.
And they would give us, you know, ideas.
And then it was a constant back and forth.
And I, I really, I take a lot of pride that I think NHRI was highly contributory to the achievement of the $1000, you know, but I immediately always point out that we did not do this alone.
29:05
And it was a beautiful example of a lot of discussion, collaboration, strategizing between the government and the private sector.
And that even continues to the present time.
And it's a really healthy ecosystem and a great way to see technical innovation where contributions are coming from both the government, from academia as well as from the private sector.
29:28
Speaker 2
We talked about the original stimulation of genomics back with the the early research and then the human Genome project leading up to the funding that stimulated the development of platforms and the science to get us to where we are right now.
29:41
The Future of Genome Research
Projecting forward, where do you think the government is going to play the biggest role in leading genomics from here and out?
Obviously we have things like CRISPR gene editing technologies.
There's a lot of really exciting stuff happening on the ground, both at the private, the research and the public level.
29:58
But when you think at that level of the NIHNHGRI, where what do you think the what direction do you think NHGRI will be pushing the research and technological development over the next 5 or 10 years?
30:13
Speaker 1
It's been a rough 2025 for NIH.
It's been a rough time for NHGRIIII, retired from federal service.
I didn't want to.
30:28
I didn't.
I wasn't given a choice.
And so, and, and five other institute directors have similarly been removed from their leadership positions.
There's a lot going on with the new administration.
It's very complicated and, and a lot of, of, of reduction in our workforce and a lot of threats budgetarily and other things.
30:53
So NIH is not in a healthy state right now.
I'm, I'm in mourning watching what's happened to an institute that I was at for 30 years where I can tell you that many of the things that we've spoken about that have led to these successes, there really is no longer the, the, the, the complete apparatus at NHDRI to continue doing some of those things.
31:19
Now it's not that it doesn't exist.
We got money, I mean, etcetera, etcetera.
But there's a lot of, a lot of parts of the institute, multiple parts, I could tell you 3 or 4 parts where all the people have, have have basically been terminated.
So I'm going to answer the question assuming a future where NIH and NHRI rebuilds to at least something resembling its former self.
31:43
If we don't turn this around, then I, I'm, I can't speak to what NHRI will do.
That said, I think the, the, the, the, the genomics advances of the future, not just going to be NHRI funded.
So I have a lot of faith in the world.
I have a faith in a lot of organizations, private sector in the United States, other funders in the United States.
32:03
And there's a lot of incredible innovation going on in genomics around the world.
And when it comes to medical applications of genomics, in some ways, other parts of the world are are are surging ahead of the United States, in part because our healthcare system is so complicated that it's not exactly the greatest place in the world to do some really important studies in genomic medicine.
32:24
Other countries that have single payers are able to go a little faster.
So I am generally optimistic that genomics will continue to surge ahead and I want to be optimistic that NHGRI and NIH is going to rebuild heal all the wounds that have happened of late and will NHRI will eventually get a new leader that and hopefully the budgets will be healthy and maybe some of the functionality we've lost will be able to get restored.
32:50
I, I truly believe that that that given on the positive rebuilding of NIH, there's a lot to be done and NHRI, importantly supported by an incredibly wonderful, talented interdisciplinary genomics community, could continue to lead and see some pretty remarkable things in the coming decade.
33:14
In 2020, in the middle of the pandemic, we published our latest strategic plan, which really charted a course for what we call the forefront of genomics, really the cutting edge of genomics.
And it was, it was basically a nice blueprint for what NH year I thought needed to be done in the coming decade.
33:34
I do think some of this is being slowed down now.
So I think we're going to lose a little of our momentum.
But once we can get that momentum back, there's a lot of really good ideas that still remain to be tackled and a lot of things that are ongoing that are the right idea of what needs to be done.
33:51
And by the way, when I say done, I mean this is at the technology level, at the basic science, understanding how the genome works, at the the translation level, understanding how the role that genomics plays in human health and disease, and then of course, actually using genomic information as part of medicine and implementing genomic medicine and precision medicine.
34:11
So I know that our strategic vision that we articulated in 2020 is still quite fresh.
You know, I think probably within another few years, maybe we'll probably going to need to renew that, because I do think there's a lot of developments that that, and you mentioned some of them including some incredible advances now going on in CRISPR based therapeutics that I think we'd want to really even push harder on the accelerator.
34:33
So I, I think I think there's a blueprint for continued incredible advances in genomics.
I think you're going to see this and we'll see it maybe a little more around the world than in the US until the US gets their act together a little get NIH healthy again.
34:52
But, but I'm very optimistic and I, I really want to once again really stress the incredibly productive and cooperative and, and, and altruistic members of the genomics community, both in academia and in the government and also in industry.
35:10
I think there's really a shared vision and a vision of excitement that that that will, will will win the day.
35:18
Speaker 2
I totally agree.
And for the record, when I talk about the EU s s strategy going forward, I also, I also look at it from the perspective of a healthy NIH and NHGRI.
It has to be.
And so, but you know, it's an interesting concept.
35:35
And when we talked about competition internally to the Human Genome project and also with Solera over the last, you know, decade or so in recent years, China has been investing heavily in genomics.
And, and, and here while we're going through this phase where we're, we're withdrawing from investing in the kind of R&D that's always made the US so competitive.
36:01
And and like you said, other countries right now will have to take on that torch of advancing genomics.
But one of the challenges with that is that they don't always share the data and the results that they learn, right?
So if it were all open source, it's like, OK, you know, we're, we're going to take a pause for four years, UK, China, you guys lead the charge and let's just make sure we all benefit from this.
36:22
But it doesn't work that way, right?
And I mean, there's the obvious privacy constraints around Human Genetics, but then there's also just a competitiveness.
And so, you know, that to me is, is a concern around the US is standing as a global thought leader in a field that's so critical to all of us, which is genomics and genomic medicine, especially as we start seeing China investing so heavily, coupled with the fact that China's also not constrained to the same kind of regulatory or privacy guidelines and laws that we have, right?
36:57
So they, they, for them, it's almost like there are no stops now.
It's just put, you know, the, the foot to the gas.
Go as fast as you can while we're over here sitting in pause.
37:08
Speaker 1
I, I, I agree with you and I, I do believe that that that key politicians, especially members of Congress, many of them understand this.
And I do think the competitiveness with China is a very important one.
37:24
And I'm hoping that will help buffer any calls for significant budget reductions or other harms to NIH, because otherwise we're going to cede our international leadership in biomedicine.
And I will tell you and I every opportunity I'm given, I, I remind somebody who's in an influential position, the number of studies that have been done showing that the return on investment, particularly in genomics since the beginning of the human genome project has been astonishing.
37:54
In general, there's good return on investment with, with, with, with the NIH funding, but in particular in NIH funding of genomics, study after study has shown a remarkable return on investment.
And we, we really shouldn't cede our leadership and we are at risk of doing that.
38:11
And China's probably the biggest threat.
But, and I do think other countries are starting to similarly see the ability to invest in to some extent.
I hope those that are willing to share on the international stage do so.
And I, I, I think we have to continually push an open agenda of when it comes to data sharing.
38:32
Speaker 2
Yeah, I agree.
And especially when it comes to the diversity of the type of data, right.
I mean, that's always been an issue in genomics to begin with.
But if we think about how complex genomics has turned out to be, from my perspective, 20-30 years ago, we were talking in a very idealistic way, which is, you know, once we sequence this, we're going to understand how all the diseases happen and then how we can treat or cure them.
38:55
And then a decade passes, 2 decades pass.
And then we started realizing actually, sure, for some types of diseases, you know, more Mendelian diseases, you can say, OK, this mutation leads to this disease.
But we're actually finding that genomics is is appearing to be more of a probabilistic, a risk stratification tool that you need to take into account along with people's lifestyles, things that they're exposed to, their diets.
39:23
All kinds of different factors are socioeconomics and genomics factors into that, plus or minus depending on the type of illness or condition that you're talking about.
But it's really not as straightforward.
And that obviously is just the very beginning of really understanding how our genomics really impacts our lifestyle in our lifetimes over the course of a human life in a way that's much more complicated than we initially anticipated.
39:49
Speaker 1
Well, you know, I often joke that, you know, there's a lot of successes in genomics, but as as the field has evolved, one thing has been very consistent.
Is it's always turns out to be more complicated than we anticipated.
You know, we the genome was much more complicated than we ever thought.
40:07
Non coding DNA in particular is much more complicated than we ever thought.
And the importance of having a lot of genomic data collected from as many people with of of different ancestries as possible is critical for both generating the sequence and for interpreting the sequence.
40:26
And so big push to get as much genomic diversity, ancestral diversity that is in in the data sets that are being generated worldwide.
40:36
Speaker 2
Yeah.
And so if we think forward, and this is the field that I'm obviously very involved in the, the translation of the research that the things that we learn in the research side to clinical practice, especially population levels.
When we start using it now for screening for healthy adults, healthy children, healthy newborns, part of the problem there is communication because thinking about genetics is the very abstract thing you need to really there, there's so much behind talking what DNA is, how it's within all of our cells and how it behaves and how it affects us.
41:08
And so a big part of it, a big part of the challenge has been how do you communicate this to the people that can benefit from it And, and in combination with that, how do you fight some of the misinformation that's potentially out there right now?
Is this something that you dealt a lot of time thinking about and acting on when you were part of the NHDRI?
41:29
Speaker 1
It I spent a tremendous amount of time I think we had first of all, I think it's absolutely central.
I completely agree with you.
I, I want to really stress the point that one of the things that genomics has to contend with is it carries with it the legacy of Human Genetics and eugenics and, and, and, as well as scientific misinformation as well as distrust in general, among especially among certain communities about science in general.
42:01
And there's, and then there's even some special nuances in some communities about, about DNA research in general at because of that, our institute has always been, or NHRI has always been very, very focused on studying the ethical, legal and social implications of the work, something called LC research for ethical Legal Social implications.
42:24
In addition to that, we built an NHRI, an incredibly robust communications program, and an education program that together really provided an outreach.
And much of this related to helping communicate about genomics, helping to improve genomic literacy, and really providing resources for teachers, for educators, for professional society, and so forth to help raise everybody's boat.
42:49
Because they people need to be comfortable with the fundamentals of genomics and they need to understand a lot of the ethical dilemmas that will be inherent with the use of genomics in medicine.
Now, I, I, I get a lump in my throat explaining all of this because on April 1st of this year, the entire communications and education group at NHDRI were terminated.
43:12
So at the moment, NHDRI has no communication staff, no education staff.
And I think in some ways we were world leaders in those areas when it comes to genomics.
So I'm not just being sort of metaphorical when I say we need to rebuild NHDRI.
43:29
I'm being serious.
I do not understand how we can provide an adequate vision and an execution plan for realizing all of the potential of genomics in medicine if we don't hand in hand think about how we're going to communicate this, how we're going to educate this, how we're going to get the next generation of patients and healthcare professionals ready for this new reality.
43:55
And at the moment, we were the world leaders at that.
And at the moment, there are various groups, but they don't have a leader.
And I'm very concerned about it.
And I was very sad when that happened.
44:07
Speaker 2
Yeah, for people that are listening that don't know necessarily some of the technicalities behind this, when there's a big distance between discovery work and clinical practice, especially at scale.
And a lot goes into how do you get these discoveries into the hands of clinicians, into the practice, within health systems, into the minds of patients.
44:32
There is translational medicine, there is implementation science.
There are a whole bunch of disciplines that go into getting these discoveries into a form, into a productized tool that can be used safely, systematically.
There is, you know, training of clinicians.
44:49
There is education of patients, there's coordination of multidisciplinary teams and health systems and so on and so on and so on.
And, and all those things are critical if you're going to be able to apply it at scale and get it to a level where everybody can benefit in a way that's responsible, equitable and safe.
45:07
And, and, and so genomics, it doesn't live exempt from that.
In fact, it's it depends on that because again, the field is so complex, it's so abstract and the science is so advanced that it's not trivial to just get it into the hands of a clinician and say here, use this.
45:27
And by the way, if.
45:28
Speaker 1
You go into the hands of the clinician.
I'm equally worried about that patient that the clinician's going to talk to.
The patient has to have some minimal, minimal literacy when it comes to genomics so they understand the language.
And we were developing so many things at NHDI for helping, you know, teach fundamental genomic literacy at multiple levels.
45:49
And you know, all of that has come to a screeching halt.
45:52
Speaker 2
It's it's terrible.
I actually did not know about that.
It's distressing to say the least, especially if we think about now how do we cope with misinformation.
We have the engine that before was creating the authoritative evidence based information and communications to the public on what genomics is and where it's going.
46:13
That's gone.
And then on the other side, we have all of this misinformation around science.
We see it rampant in vaccines, but in genomics, it's going to be equally as as critical and as deleterious.
It really poses the question of how and I don't even know the answer.
46:32
I mean before at least I could postulate how we deal with misinformation when we would have a government organization dealing with the the the evidence based information.
I don't know how we deal with the misinformation now given what I just learned about the NHDRI.
46:47
Speaker 1
No, that's absolutely right.
I mean, so we will we, we have no, no defense against this.
And by the way, go back to your earlier concept about competitiveness in the world, One of the things I think we were doing quite effectively was getting students excited about genomics and teaching them that you could be involved in genomics by going to law school, by going to Business School, by going, you know, to medical school, obviously Graduate School, pharmacy school, nursing school.
47:14
We saw all this.
So we were trying to do was to think about the next generation.
So we had expertise and, you know, we're not stimulating that now.
And meanwhile, I think other countries like China, I mean they're just going to, they're just going to train a ton of genomicists and they're going to out compete us.
47:31
Speaker 2
Yeah.
And and potentially lure a lot of the talent that we used.
47:35
Speaker 1
To There's a lot of that going on, especially in Europe, trying to lure US scientists there.
47:39
Speaker 2
Yeah, I can imagine.
So if we turn maybe to just forecasting into a future where NIHNHERI are fully functional and healthy, they're still, we're still at the just beginning phases of genomics.
47:54
The most promising areas of innovation in genomics
I feel that way.
And and you know, we, we've come so far clearly as we've spoken about it, but there's just so much that we don't know what what do you see as the most promising area of innovation in genomics that would have the most transformative impact in medicine in the next decade or so?
48:14
Speaker 1
Yeah, I'm not sure I see a single thing.
I mean, I, you know, you can't help.
There's some recent news about that came out just last week, a remarkable story where an individualized CRISPR based technology was used to to really probably save the life of a child that otherwise would have had a fatal genetic disease.
48:35
You know, I think genome editing and genome based therapeutics is has some incredible opportunities, some of it for rare diseases, but similarly, we're seeing this in in, in, in certain types of therapies for cancer, cell based therapies for cancer.
48:52
I think we're just scratching the surface of some of these therapeutics.
It's actually not something that I directly worked in a really not much any, any sure, I only had a small footprint in the therapeutic space, but I sit in awe and seeing some of the technical innovations that are happening around genome editing.
49:08
And, and of course, we should also realize that, you know, the CRISPR base method is just one method, certainly will be others.
And there's a lot of exciting work being done and developing other genome editing capabilities.
You know, I, I, I certainly think about a world where we have more and more abilities to use genomic information for prevention and, and, and, and really making sure that those capabilities match the discoveries that are being made and thinking about, You know, what does the future world look like?
49:44
Some of that will relate to the health ailments, but some of the prevention will be preventing the wrong medication being given to somebody or the wrong dose and a whole field called pharmacogenomics.
And so, you know, it just seems that there's a series of, of, of, of, of bits and pieces of information and various clinical niches that I think are going to slowly but surely build up momentum for the idea of, of, of getting genomic information, complete genomic information of an individual early in their life.
50:17
I know it's something you're quite involved in, in this idea of, of, of should we be taking every newborn maybe and sequencing their genome or if it's not at a newborn stage, some early stage?
I, I, I really do see there's going to be a tipping point at some point.
I don't think it's a matter of if, I think it's a matter of when, where people are going to just recognize and having complete genomic information as, as available on call through an electronic means, like an electronic health record or some website is going to become sort of desirable.
50:51
I think other countries are going to teach us this first because they're surging ahead and doing some of these studies.
But I think the, the, the literature just keeps growing and growing and growing of the kind of information that will be, that will be useful.
And I'm very excited about that future.
I, I think as always, we have to appreciate that most human health conditions are complicated.
51:11
It's not all genomics.
So I don't want anybody listening to this to think that we're going to be in a position of absolutely predicting accurately who's going to be hypertensive, diabetic, you know, asthmatic, etcetera, etcetera.
I fully appreciate there's a lot of physical and social environment contributions.
51:27
The social determinants of health are incredibly important, but I think there's a lot more attention to those areas as well.
And, and I also, you know, sometimes people to portray genetics versus environment as if it's, it's competing with each other for attention.
51:43
And I, I can tell you at NIH, there's a lot of interest at the intersection of those areas and a lot of studies that are going on to, to facilitate research at the intersection of those areas.
And, you know, we're also entering the other thing I'm pretty excited about and, you know, because it cuts across all this, you know, the the amount of data and the amount of data tools.
52:08
And, you know, you always want to throw in artificial intelligence and of course, and machine learning.
And of course, I mean, there's such data sets that are available that just, just, I just know there's going to be discoveries that we never could have anticipated because we're going to use these new computational tools in ways that the human brain just doesn't work as well and, and make discoveries.
52:32
You know, So I, I, I just tell young people all the time, it just couldn't be a more exciting time than now to, to do something that's going to touch genomics because there's just going to be a lot of developments going forward.
52:44
Speaker 2
I love that.
And for the record, that's the area that excites me the most about this is really how do you use all the determinants of health?
For me, precision medicine, a lot of people hold it a synonym for genomic medicine.
And in a way, genomic medicine has been leading the charge there because of the amount of data that we've been capturing.
53:02
But the reality of precision medicine is how you use all of the data available to be able to gather a much more precise view of the patient, where they are and their environment in a in a way that you can potentially predict their health outcomes and potentially intervene when you see something negative happening.
53:19
And so to your point, as we're gathering data, not only in genomics, but more in socioeconomics, environmental factors, how behavior factors into this and, and obviously genomics and, and heredity, I think as we apply now this layer of AI on top of that to start understanding the relationships, these very complex longitudinal relationships that are just not very intuitive.
53:43
I think it's where for me where medicine starts becoming really, really fascinating.
53:48
Speaker 1
No, I agree with you.
I always, I always describe genomic like a Venn diagram.
Genomic medicine is within a circle, the bigger circle being precision medicine or personalized medicine or individualized medicine.
But you know, genomic medicine is a subset of that because that's giving you information about the genome, but there's all the other information about people's lives.
54:08
Speaker 2
Yeah.
So just to close off a question you mentioned of young minds right now thinking about the future of this and, and you talked about various different technologies from CRISPR to AI.
54:21
Advice for future innovators
If you could give advice to future innovators in this field and the direction that you know, because going in all the opportunities and challenges with it, what kind of advice would you give to say, college students right now saying like, wow, that what, what Doctor Green did with a human genome project and NGRI?
54:39
That's very cool.
I I'd like to model my future in that direction.
54:44
Speaker 1
Yeah, I would, you know, and I do talk to young folks all the time at different levels.
And I, I would, I would, I usually give 3 bits of advice.
First thing, the 1st 2 are interrelated.
First thing is don't worry so much.
54:59
I, I always tell, I, I think younger people these days, they look at the world because the world's a crazy place right now and they just get worried.
And I, I, I, I do think, you know, we have some challenges right now, at least in the US, but, but just look at the successes of genomics.
Look at the community, look at the people who have built this field and there's a big tent and, and, and don't worry so much and please come into our tent.
55:22
The second thing is something we we touched on earlier is, but you know, come into the tent, but don't worry about all the micro details.
Just get excited about something and don't worry about your exact path, your exact journey.
You know, if it doesn't feel right, shift a little and if it feels right, go for it.
55:37
And don't let people dissuade you.
If if you're really enthusiastic, the the most practical thing, I guess I say, and maybe it's just a reflection where I feel that I'm, you know, I if I was a student again, what would I need is what we were just talking about.
I mean, genomics is data intensive.
55:53
It wasn't that way when the field got launched.
It wasn't even that way when the genome project ended, when we had one human genome sequence.
But nowadays, if you're going to do any serious, you're going to be at the research level or even the genomic medicine level.
Get comfortable with big data sets.
56:11
It doesn't mean you just need to be a power user.
You don't need to, you know, developing all the algorithms.
You can leave that to somebody else.
Doesn't have to be hardcore computational work.
Just feel comfortable and facile at manipulating large data sets using publicly available tools.
56:27
You're just going to need to know how manipulate big data because genomics going forward, it is very data intensive and you're going to have to be comfortable with that.
56:37
Speaker 2
Perfect advice, I couldn't imagine a better way of ending this.
Doctor Green.
Just want to take a moment to and thank you for all of the work that you have done throughout your career, from helping to lead so much of what the Human Genome Project turned out to be, all the way through helping to stimulate and lead the world of genomics for the US and for the world.
56:59
It's extraordinary.
And I'm honored to know you.
I'm honored to have interviewed you, and I can't thank you enough for having been here.
Thank you so much.
57:08
Speaker 1
Well, thanks, Nic.
This has been a pleasure.
It's been great talking to you.
