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Appropriations Subcommittee Statement on the Fiscal Year 2010 Budget

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May 21, 2009

Mr. Chairman and Members of the Committee:

I am pleased to present the Fiscal Year (FY) 2010 President�s budget request for the National Institute of General Medical Sciences (NIGMS). The FY 2010 budget includes $2,023,677,000, which is $25,876,000 more than the FY 2009 appropriation of $1,997,801,000.

Each year, NIGMS-supported scientists uncover new knowledge about fundamental life processes. While answering basic research questions, these scientists expand our awareness and understanding of how disease takes hold in the body. Institute grantees also develop important new tools and techniques that have research and medical applications. The payoffs from NIGMS research investments are impressive on many fronts. As just one example, 67 scientists have received Nobel Prizes in recognition of the scientific breakthroughs they made with NIGMS support.

Genetic Studies Guide Treatments

The future of medicine will center on precise diagnosis and personalized treatments. This is a departure from most of today�s medical approaches, which are based on studies of populations and one-size-fits-all statistics derived from them. The ability to preemptively tailor health care to individuals offers huge potential for increasing the efficiency and effectiveness of efforts to preserve health over the course of a lifetime.

Americans are eager for information that will help them make intelligent, individualized choices about their health. Toward this end, in 2000 NIGMS partnered with a number of other NIH components in launching an effort to determine how genes affect the way people respond to medicines, including antidepressants, chemotherapy agents, and drugs for asthma and heart disease. Since then, studies by this Pharmacogenetics Research Network (PGRN) have shown that genetic information can help predict how beta-blockers, breast cancer medications, and nicotine patches will work in a specific person. In early 2009, PGRN researchers merged data sets from around the world to demonstrate that information about certain genetic variations could aid doctors in determining the proper, personalized dose of warfarin, a blood-thinning drug taken by millions of Americans. This work set the stage for a prospective clinical trial that will test if using such genomic information will make it quicker and easier to get the right dose and furthermore, whether doing so could prevent serious treatment complications like heart attacks, strokes, and internal bleeding.

Other NIGMS-funded genetic studies have revealed surprising roles for RNA. Nobel laureates Andrew Fire and Craig Mello paved the way for this paradigm shift by showing that a process called RNA interference, or RNAi, silences the activity of targeted genes. RNAi is now being widely used both as a research tool and for the development of products that could combat diseases like cancer and HIV. In 2008, other NIGMS-supported scientists won the prestigious Lasker Award for their groundbreaking discovery of microRNAs, short RNA molecules that regulate gene function using some of the same mechanisms central to RNAi. Our rapidly expanding understanding of RNA�s many roles is already providing novel medical insights, such as the linkage of abnormal microRNA levels to cancer and other diseases.

Physical Sciences Shine Light on Biology

The intersections between fields of science�such as those between the physical sciences of physics, chemistry, mathematics, and computer sciences and the biomedical and behavioral sciences�often yield particularly fruitful and high-impact lines of investigation. One timely example is the NIGMS-supported computational modeling tools being used to predict the spread of emerging infectious diseases and the results of possible interventions. These field-spanning approaches provide important insights to help policymakers and public health officials respond to outbreaks, including H1N1 flu.

Further evidence of how basic physical science can greatly contribute to biomedical research is found in nuclear magnetic resonance, or NMR. This technique, developed by physicists in the 1930s, underlies the well-known medical procedure of magnetic resonance imaging (MRI). But in the laboratory, NMR is the basis of some of the most powerful analytical methods in chemistry and biochemistry. In 2008, NIGMS-funded researchers used NMR to identify a contaminant in several batches of another widely used blood-thinning medicine, heparin. The scientists determined the chemical structure of the contaminant, which was only subtly different from heparin and therefore difficult to find by other methods, and showed how the contaminant could cause severe reactions and even death in humans. As a result of this work, NMR may now be used to screen additional drug preparations for contaminants that are difficult or impossible to detect by other means.

A physics-based technique called X-ray crystallography is also key to understanding molecules that are central to health and disease. Using this approach along with NMR, scientists funded through a coordinated NIGMS effort called the Protein Structure Initiative, or PSI, have produced a wealth of information about the shapes of proteins, which are essential to their functioning. Following successful pilot and production phases that included the development of critical tools and techniques, the Institute is now focusing the PSI on structures with specific biological roles and expanding its reach throughout the scientific community. This new direction, called PSI:Biology, will emphasize partnerships between biologists and high-throughput structure determination centers to address important biomedical problems and provide information that will aid the development of new medicines.

Among the advances from chemistry studies are powerful imaging techniques that allow scientists to visualize life processes in unprecedented detail. The discovery and development of green fluorescent protein (GFP) is a case in point. GFP was first purified from jellyfish in 1962, and before long, NIGMS-funded American researchers were finding ways to use this new tool to monitor activities in living cells and organisms. These scientists, who won the 2008 Nobel Prize in chemistry for their insights, put the GFP gene into a variety of organisms, including bacteria and worms. Today, GFP is an essential part of the fabric of biological research and is used, for example, as a key component of powerful drug development tools.

Finding and Funding Innovation

To keep knowledge streaming from the nation�s scientific laboratories, we must be agile in responding to the changing needs of researchers, both individuals and teams. The Institute has been a pioneer in novel funding programs that address the needs of the scientific community and encourage innovation. One good example is Konrad Hochedlinger, who received an NIH Director�s New Innovator Award in 2007. This program, which NIGMS developed and administers, jump-starts the careers of unusually creative early stage investigators. Since groundbreaking work in 2007 in which other NIGMS-funded scientists reprogrammed ordinary skin cells to become induced pluripotent stem cells, or iPS, this area of inquiry has exploded. Dr. Hochedlinger�s project aims to unravel the many details of how reprogramming works. He is currently working on creating "reprogrammable mice" in which every cell can become an iPS cell capable of morphing into any cell type.

Another New Innovator is explaining basic behavioral principles using animal models. Karin Pfennig is studying how different species of toads choose a mate, a decision that has costs and benefits and involves trade-offs. Understanding the fundamental drivers of such "context-specific" behavior may help us treat behavioral disorders in people and address behavioral aspects of disease transmission and spread.

Dr. Pfennig has contributed to the research enterprise in another important way. As part of its commitment to training the next generation of scientists and increasing the diversity of the scientific workforce, NIGMS developed the Institutional Research and Academic Career Development Award (IRACDA). This program gives postdoctoral scientists mentored teaching experiences at minority-serving institutions. Through IRACDA, Dr. Pfennig pursued her own cutting-edge research at the University of North Carolina, Chapel Hill, while also teaching at a historically Black college, North Carolina Central University. Dr. Pfennig, who grew up in a single-parent household with very limited resources, attributes her desire to "give back" to her own great teachers and mentors who challenged her to pursue her ambition to become a scientist. Programs like IRACDA pay lasting dividends on many levels, providing role models for students, preparing future teachers, and promoting partnerships between institutions.

Investing Today for American Prosperity

In addition to building a solid foundation of knowledge for medical advances, basic biomedical and behavioral research yields tangible economic benefits. NIGMS grants support the salaries and laboratories of thousands of researchers throughout the United States. And NIGMS-funded advances have played a significant role in the development of the multi-billion-dollar biotechnology industry, which is now its own engine of discovery as well as a critical partner to the pharmaceutical industry.

I want to close by affirming the Institute�s deep appreciation for the extraordinary opportunities provided by the American Recovery and Reinvestment Act of 2009. In addition to its impact on stimulating the nation�s economy, this legislation will enable scientists to uncover new knowledge that will lead to better health for everyone. We intend to use these funds to support highly meritorious research that could not be funded with our regular appropriations and to further accelerate the tempo of science through targeted supplements to existing grants. NIGMS is also addressing research projects which are consistent with the President�s multi-year commitment for Cancer and Autism. We are also eager to fund creative studies sparked by the new NIH Challenge and Grand Opportunities grant programs, which are designed to focus on health and science problems where significant progress can be expected in two years.

Thank you, Mr. Chairman. I would be pleased to answer any questions that the Committee may have.

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