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Q&A: Mark Guyer on the NHGRI's Expanding Role and the Future of Sequencing

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guyer.JPGName: Mark Guyer
Title: Deputy Director, National Human Genome Research Institute
Experience: Director, NHGRI Division of Extramural Research;
Program director, National Institute of General Medical Sciences;
Served as an initial staff member of the Office of Human Genome Research, 1988
Education: PhD in bacteriology and immunology, University of California, Berkeley, 1974

The National Institutes of Health recently tapped Mark Guyer as deputy director of the National Human Genome Research Institute. Guyer has been involved with the NHGRI for the past 23 years, where he has been involved with the Human Genome Project, other large-scale sequencing projects, the creation of the Ethical, Legal and Social Implications program, as well as the development of NHGRI's five-year strategic plans.

The most recent of those plans was published last February in Nature, and will serve as a guide to the types of projects the NHGRI will fund over the next several years.

One key difference that has emerged in the current plan, compared to previous plans, is that it is more specific in charting a path toward the adoption of genomics in a clinical setting, and provides more details on the necessary developments to move toward genomic and personalized medicine (IS 2/15/2011).

Guyer, a co-author of the plan, recently spoke with In Sequence about his role at NHGRI, the development of sequencing technology, and NHGRI's "expanding" role in genomics.

What will your new role at the NHGRI entail?

The deputy director is involved in advising the director and carrying out special projects related to the entire institute. So the difference between what I was doing as director of extramural research and [now as] deputy director will be a wider responsibility across the entire institute.

Can you talk about how NHGRI's role has evolved in the last several years, and where do you see it going in the coming years?

As one of the authors of the strategic plan, the answers are all in that. The NHGRI has been a leader in the development of the field of genomics and aspires to continue to play that role.

As genomics becomes more ingrained in all aspects of biomedical research and makes an increasing contribution toward the ability of research to contribute to improvements in human health, NHGRI will work in those areas appropriately.

The strategic plan indicates that the field of genomics has new opportunities and new demands that will lead to the expansion of applications in medicine, genomic medicine, and NHGRI intends to contribute significantly to those.

Do you see NHGRI moving from a research-oriented focus to having a more clinically oriented mission?

No. Actually, within the constraints of the budgets that we have, the activities of the NHGRI will expand, rather than shift.

NHGRI believes that there is still an enormous amount of important work to be done in areas that are generally considered to be basic research, basic understanding of biological mechanisms, and disease mechanisms, and much of our activity over the next several years will be focused in the areas we identified in the strategic plan — the understanding of biology of the genome and the understanding of biology of disease.

What types of research projects do you anticipate focusing on, and have those shifted or evolved at all?

They're not going to shift, they're going to expand. We will look for new opportunities in both genomic science and genomic medicine. And there are many ideas that are under discussion, but as of now, the programs that we've already announced are what we're focusing on.

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Where do you see sequencing technology going, and how do you see that technology evolving and developing?

I think that in one sense, I hope that technology developments will continue on the trajectory that we've seen for the last decade: constantly decreasing cost and addressing issues of accuracy and continuity. Issues of reflecting the enormous variation in populations are issues that are going to have to be addressed by sequencing. The use of sequencing in diagnostic and clinical applications is an area for development.

What improvements need to be made before sequencing becomes widespread in diagnostics and clinical applications?

Improvements in the technology will be most important in the areas of accuracy and reliability. Certainly, further reductions in cost. Speed will be necessary. But the other major aspect of what's going to be needed before sequencing becomes routinely diagnostic is analysis and interpretation — understanding what the physiological and biological consequences of variation are.

As sequencing moves toward clinical applications, how will that impact or influence the focus of NHGRI?

I think the question is coming at it from the other direction. I think NHGRI is going to be influencing the ability of sequencing to be used even more broadly in research and ultimately in healthcare delivery.

So, then how will NHGRI influence the ability of sequencing to be used in a healthcare setting?

By making the technologies available to the larger community of scientists and clinicians who have the biological expertise to know what data to gather and how to interpret it.

NHGRI last year said it would renew funding for the large-scale sequencing program for another four years, but also separate funds out of that program to support the Mendelian Disorders Genome Centers and the Clinical Sequencing Exploratory Research program (IS 12/21/2010). What types of projects will you fund under those programs, and why did you decide to separate them out from the overall Large-Scale Sequencing Program?

They were separated out because we saw opportunities in those areas that we thought would be best pursued by dedicated research projects in those areas, rather than the broad, more general sequencing activity in the large-scale sequencing centers. So we made the decision to reduce the level of funding in the large-scale sequencing program by a modest amount, about 20 percent, in order to generate the funds to take advantage of these new opportunities.

What types of projects will you be supporting under those umbrellas?

I can't tell you who's going to be funded. But the types of projects we're looking for ... in the Mendelian program [are] highly efficient, high-throughput sequencing centers that will use sequencing to identify the genetic basis of a large number of Mendelian diseases, taking advantage of the recent developments that show that you only have to sequence a few individuals for each of the rare diseases to identify the causative genetic variant.

In the clinical sequencing program, there's a broad range of projects where people think that they will be able to use sequence data in a way that will directly affect clinical decision making. So the projects that we'll be supporting [will] test the hypothesis that that can be done. Those awards will all be announced later in the year, November and December, and until then, we can't say anything more specific.

Does the fact that you've created these two separate programs suggest that the technology is maturing to the point where it's more focused on application rather than technology development?

No. I think it indicates that the technology has matured to the point where it's adequate to be used in those kinds of research projects, but not to the point where more sequencing technology development isn't needed.

How will NHGRI be involved with the regulatory side of things as sequencing moves toward the clinic?

To the extent that we can provide technical advice, I'm sure we'll be called upon, but in terms of actively participating in regulatory decision making … that's not the mission of NHGRI.

Is there anything else you'd like to add?

The vision that we discussed in the recent strategic plan was a vision for the field of genomics, not specifically for the NHGRI. And it is our hope and expectation that the research and development community will invest and take responsibility for doing a lot of the necessary work.

NHGRI has a fixed and limited budget and we will not be able to support everything that needs to be done and for which the science has created phenomenal opportunities.

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