The Strategic Plan: Interview with Eric Green, M.D., Ph.D.

So our strategic plan probably has multiple audiences. For starters, the genomics community is a community of scientists I think that for many years that followed a series of strategic plans as sort of a vision if you will about what the most compelling opportunity in genetics and genomics for the next set of years. But I think there is another audience, as well. I think those audiences include students. Students both in the basic sciences and clinical sciences and individuals who are thinking about the future clinical medicine. But also students in law, students in ethics, students in sociology public policy. Genomics is perfusing many areas in society, as well as science, and the next generation of scholars need to be much more aware of what happening in this field. I also think the audience includes those of us in the institute we need to think about what the most compelling opportunity in genomics are and how we want to tailor our program to maximize the benefits and the opportunity. So having that document prepared by us is really created an opportunity but think critically about what we should be doing as an institute.

Then in 2003, it was very clear with the end of the human genome project that there were some very exciting things that can be done having in hand, sequence the human genome, and incredible opportunities but we wanted to have a more articulated vision of what those opportunities might look like in the next five to ten years. And so at that point once again the genomics community got together under the leadership of our institute and put together a strategic vision. And that 2003 strategic vision has guided us well really taken advantage of incredible things that one might do, having the first look of the human genome sequence and pursuing some of the things that were very compelling at the time. Seven years or so later, a lot of things have changed. And it was time once again that the genome community think critically argue debate and re articulate a vision for genomics research with a vision that is much more acute now that we sort of enter the second decade of this new century. And so this one, that we are publishing, will be the 2011 Vision for Genomics Research by NHGRI is much more clinically oriented, thinking much more about clinical applications of genomics and many ways more expansive than the earlier visions were, but at the same time starts to get us closer to the kinds of promises that were made originally when the human genome project was first envisioned.

And so we describe these five domains, some of which that have been very active this past decade, but others are more far reaching, but nonetheless, we want to think about research agendas that will really inform us and make us more sophisticated in those domains. It starts at the most proximal end of that progression by simply understanding the structure of genomes, sounds like what we did in the Human Genome Project and certainly included activities that have been going on since the Human Genome Project. But then it's about understanding how the human genome works and advancing our knowledge of genome function and that was very importantly and certainly was a major emphasis of our strategic vision starting right when the genome project was completed. The third domain starts to apply that knowledge of genomics to advance our understanding of human disease. And here is the progression that in many ways the fields of genomics is most aggressively pursuing really using the tools and technology of genomics to better understand molecular basis of disease. The fourth domain then moves you from having that knowledge of disease to actually changing medical science by advancing how you approach medical science. There you start to see clinical applications but you can't stop there, and this was one of the key things we heard from our colleagues in genomics community and members of the biomedical research community who has had experience in taking discoveries all the way to the bedside. Now there is even a fifth domain that one needs to contemplate and that's actually demonstrating effectiveness of these advances to the actual delivery of healthcare. Just because you have a medical advance doesn't mean that it's actually going to prove to be effective when actually executed in the healthcare delivery study. You need to actually have a research agenda that studies that last area if you're ultimately going to have an impact on clinical care.

This is a global effort and it's really important just to recognize that many of those things we're talking about will not be just confined to the genomics community. Genomics is perfusing all areas of biomedicine. This is I think fantastic and most importantly many of the things that we talk about in our strategic vision will be carried out by other fields of study. Some cases in partnership with us, and some cases they don't even need to be in partnership with us. The way you execute it is we'll figure out what we do best as an institute. We'll work with our colleagues here at NIH at other institutes to think of what we can do with partnerships and there are some things that we expect other agencies, other organizations, and other countries to jump in and help as well.

One of the other reasons for describing the strategic vision around five domains is also to help predict where you might see development in the coming years. Just in the past decade for example, we have seen spectacular advances in understanding the how the genome works and how it functions and certainly how the structure of genomes. We think that in the next decade is going to bring additional advances and understanding how the genome works to levels of details that are critically important in many ways previously unimaginable, but at the same, the next decade we will see a big spike in our knowledge of the molecular basis of human disease. And they'll be some advances that will fall into the domains related to advancing medical science, and demonstrated the effectiveness of health care, but we don't think that they will be hot areas in the next decade realistically they'll be examples..but we have to be realistic here, those advances actually changing medical care, sometimes that takes decades. We think they're going to happen, but we have to be cautious in predicting that it will all happen in great numbers in the next ten years

This is a transitional point in genomics in many ways, I firmly believe that we had to wait for the right time to really believe that we knew enough and that we had the tools and technology in hand to start that transition. And much of this being catalyzed by technological advances especially in DNA sequencing methods that have seen a complete change in the cost models of sequencing genomes such as the cost of genome sequencing have been plummeting for the past four years. And as a results of that what seemed way out there and decades away now all of sudden seems to be in reach and as a result it creates new opportunities and puts us into a new landscape that was previously unimaginable and quickly puts us into an arena where clinical applications become very realistic.

I think the sense of urgency is as much as a realization that this can truly change the practice of some aspects of medicine and you can point to very specific examples and I think the one's that you are going to see are most clear in the next two or three years because we are already seeing it in cancer, for example. Cancer is a genomic disease and the fact that we can now use these powerful new sequencing technologies and comprehensively catalog genetic changes that take place in a tumor and have that information point to the best path forward for treating a given individual is very compelling. And while there are a handful of examples where that's the case so far, we have in place we think programs that will reveal many opportunities for making that progression in different types of cancer in the next five years. And that make one feel very urgent because you feel like this truly can make a difference.

I think it's part of the essence of genomics, technological advances. A and so far in the past five years for example, the real push in technology has been Iin the area of DNA sequencing so we could sequence genomes very cost effectively. Now that just creates a new bottleneck that has to be dealt with and we need new technological approaches to solving those. For example, when you can sequence genomes very inexpensively it results in a massive accumulation of data. So much so that it actually overwhelmed investigators which overwhelmed clinicians so we need technological advances to deal with all that data to make that information interpretable to reduce it to practice it in a clinical setting that all requires major technological advances.

Once upon a time, probably when the Genome Project was first envisioned, we thought it was all in our genes - if we just understood the gene sequences, we would understand all of human biology. Now we know that genes are maybe less than a third of all the functional parts of the human genome. There are all these non-coding sequences that are so functionally important and it turns out a lot of those contain variants that are conferring risks for common genetic diseases. We barely have our heads around that, and then you hint that it's not all about the A's, G's, T's and C's because we now know that there's all this epigenomics going on where DNA is being decorated with different chemical groups and that has a language in itself and that language can be changed an altered in disease. And then if you get away from DNA, then there is environmental contributions as well. Those are important. All of this is being studied, but technologies are available for some more than others. And so we are strong right now. Our technologies for studying DNA, including for epigenomics, where we are hoping to get better technologies, where we will be able to monitor the environment and being able to punderstand exposures - all these things are being pursued. They all need to come together to really take full advantage of what could possibly happen in genomics and human genetics with these new opportunities that we see before us.

So a lot depends on what you mean by personalized medicine. I's not going to happen all at once. I would contend that it's already starting to happen. I think you will see an increasingly growing lists of genetic tests that are relevant as part of standard of care. I think you will see interdiagnostic tests developed and implemented for disorders such as cancer before you see for lots of other disorders. Already we are seeing individuals going to get their genome analyzed not through their doctor's office but through companies directly. I think you'll see a progression were at some point that it might be done more in doctors' offices but there are a lot of steps before we could get to see that routinely. So I don't think it will be a year or a moment that all of this will happen. But what we want to do at NHGRI is facilitate and establishment of a research agenda that will help us answer many questions that need to be answered affectively before we can really think about implementing this on a large scale. But we think we have a much better idea of what some of those questions are now we want to build a research program to help answer those questions.

I'm absolutely satisfied, I think there have been spectacular advances in the field I think what we tried to describe in the strategic plan is not only a capturing of what we've done so far but to show the confluents of all these things that have happened the far reaching set of things that can now be approached for the first time and the compelling reasons why we want to go there because of the applications it can have for medical care.