Mr. Chairman and Members of the Committee:
I am pleased to present the Fiscal Year (FY) 2009 President’s budget request for the National Institute of General Medical Sciences (NIGMS). The FY 2009 budget includes $1,937,690,000, an increase of $1,882,000 above the FY 2008 enacted level of the budget, which has been adjusted comparably to reflect HHS proposed transfers.
This is a remarkable time in science. The sequencing of the human genome has provided an unprecedented framework for understanding human biology and advancing medicine. We now have a clear measure that all human beings are nearly identical at the genetic level, differing by an average of one letter of the genetic alphabet out of a thousand. Yet it is these differences that make each of us unique and contribute to our individual susceptibilities to particular diseases. The future of medical research will be dominated by our efforts to understand these individual differences and translate this understanding into improvements in health care, including reducing costs through disease pre-emption. Basic research funded by NIGMS has yielded deep insights and powerful tools that are essential to achieving this promise.
To demonstrate the rapid application of basic research to clinical practice, consider the example of Huntington’s disease. This degenerative neurological disorder affects approximately 30,000 Americans, according to the Hereditary Disease Foundation. It is caused by a long series of repeats of three genetic alphabet letters—so-called triplet repeats—in a gene expressed in brain cells. We all have short series of repeats, but they are longer and appear to expand over time in people with Huntington’s disease, eventually reaching a length where they contribute to cell death and disease symptoms.
How do the triplet repeats expand? Our cells contain many systems that protect our genomes when DNA is damaged. Test-tube studies by NIGMS grantee Cynthia McMurray at the Mayo Clinic demonstrated that expansion of the triplet repeats associated with Huntington’s disease is a side product of such a DNA repair pathway.
But does this happen in living organisms? An elegant way to address this question is to inactivate key genes involved in DNA repair and examine the impact on triplet repeat expansion. In the mid-1980s, NIGMS-funded researchers Mario Cappechi of the University of Utah and Oliver Smithies of the University of North Carolina invented methods to disrupt, or “knock out,” virtually any gene in the mouse genome. This breakthrough, which revolutionized biomedical research, was recognized with the 2007 Nobel Prize in physiology or medicine. Dr. McMurray used a strain of mice developed with this technology to have one critical DNA repair gene knocked out. She discovered that triplet repeat expansion was, indeed, dramatically reduced. This suggests a novel strategy for pre-empting Huntington’s disease: developing drugs that specifically inhibit this repair pathway.
While many hurdles must be overcome to fully capitalize on these advances, we can now envision a day when individuals predicted to develop Huntington’s disease based on a genetic test could take a drug to slow or stop its development, reducing both suffering and treatment costs. Furthermore, because triplet repeat expansion appears to underlie additional genetic diseases, this personalized and pre-emptive strategy could potentially be adapted to other serious health conditions.
The development of small-molecule drugs directed to specific targets like the Huntington’s disease repair pathway is a productive, but relatively traditional, approach to disease treatment. Periodically, basic researchers make discoveries that open up entirely new approaches to promoting health and treating disease.
Last year, for example, I highlighted the Nobel Prize-winning discovery of RNA interference, a newly elucidated mechanism for controlling gene expression. Novel drug candidates that harness RNA interference are now in clinical trials for a range of different conditions. A few months ago, scientists made another such paradigm-shifting discovery. In November 2007, two research teams reported that ordinary human skin cells could be transformed into cells that appear to look and act just like embryonic stem cells. One of the teams, led by James Thomson of the University of Wisconsin, was funded in part by NIGMS and the National Center for Research Resources. In related work made possible by the NIH Director’s Pioneer Award program and announced in December, George Daley and his team at Children’s Hospital Boston achieved the same goal.
Cells that can become any of the hundreds of cell types in our bodies are an enormously useful tool for researchers studying diseases and drugs in the laboratory. In time, with further analyses and testing, these cells may provide truly personalized treatments for people suffering from a wide array of health problems. The nearly simultaneous development of the methods is not an accident, but rather reflects the impact of basic studies on human and mouse embryonic stem cells that revealed the genes most critical for defining stem cell properties.
It is important that NIGMS keeps its eye on the horizon, anticipating needs by staying in close touch with the scientific community and the public we serve. We have recently issued a 5-year strategic plan, Investing in Discovery, that articulates our core principles and shows how we will make decisions to ensure the stable basic research environment so vital for sustaining progress in biomedical and behavioral science.
Our principal, time-tested strategy is to support competitive, investigator-initiated studies aimed at a wide array of biomedical problems. One strength of the NIH funding system is its flexibility. For example, when Dr. Capecchi submitted a grant application in the early 1980s for studies that included the work leading to his Nobel Prize, the external scientists evaluating his proposal expressed skepticism about this experiment but still scored the application highly. NIGMS funded the grant, giving Dr. Capecchi the freedom to pursue the avenues that culminated in his prize-winning achievement.
We are concerned that many creative researchers, especially those just beginning their journeys of exploration, may never get the chance to pursue great—yet risky—ideas whose results could provide the cures of tomorrow. To help address this issue, we have developed the new “EUREKA” grant program based primarily on the innovativeness and potential impact of a scientist’s idea. We eagerly await the outcomes of this program, which has already stimulated considerable interest in the scientific community as well as among other NIH components.
Today’s biomedical research enterprise is highly collaborative. Cutting-edge research may involve one or a few laboratories or a large group of scientists. As noted in our strategic plan, we endorse the scientific community’s ability to self-assemble into multidisciplinary teams to tackle large, complicated problems. The NIGMS portfolio includes several large-scale science programs, such as the Large-Scale Collaborative Project Awards (glue grants), National Centers for Systems Biology, Pharmacogenetics Research Network, Protein Structure Initiative, and Models of Infectious Disease Agent Study. All are making progress toward their directed goals and in other ways, such as by developing a range of resources of broad value to the scientific community.
Another benefit of the Institute’s investments in large-scale programs has been drawing in new researchers. Among them is Mavis Agbandje-McKenna, a young scientist at the University of Florida who was trying to obtain her first independent NIH funding. She sought collaboration with the Consortium for Functional Glycomics, one of the NIGMS glue grants, and gained access to its state-of-the-art resources and expert scientists. This allowed her to pursue studies about viruses and their ability to cross species. With a start from these resources, she succeeded in becoming an independently funded investigator with an NIGMS research grant.
This example points to the importance of maintaining a healthy balance of research investments. The freely available tools and resources that emerged from the glycomics consortium have jump-started many studies. This has enabled investigators like Dr. Agbandje-McKenna to apply their unique skills to speed discovery in important areas.
NIGMS is committed to fostering a strong, stable, and diverse scientific workforce. We define diversity broadly—spanning ethnicity, gender, disability, socioeconomic status, and national origin. In order to maximize participation in the biomedical research enterprise, our young scientists need role models like themselves, and, if our nation is to retain its global leadership in science and technology, it is essential that our workforce—including its top ranks—accurately represents our population. The challenge of increasing scientific workforce diversity is fundamentally a systems problem, and we are approaching it that way. We will continue to acquire data and invest in research on the efficacy of interventions to enhance diversity.
As I noted earlier, studies based on the human genome are enabling scientists to make striking new connections between fundamental aspects of biology, human health, and disease. To produce a level of understanding useful for translation into clinical strategies, we often need more basic research on newly discovered targets, such as genes associated with common diseases. Future medical research progress depends on a well-prepared and diverse scientific workforce with access to powerful tools and appropriate support mechanisms. The knowledge we generate from these investments will bring us closer to personalized, pre-emptive medicine and the goal of better health for all.
Thank you, Mr. Chairman. I would be pleased to answer any questions that the Committee may have.
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11/27/2015 11:42 AM
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