Lawrence A. Tabak, D.D.S., Ph.D
Principal Deputy Director
National Institutes of Health
U.S. Department of Health and Human Services (HHS)
Numerous Public Health Bills
Committee on Energy and Commerce
Subcommittee on Health
United States House of Representatives
Tuesday September 14, 2010
Mr. Chairman, Members of the Subcommittee, I am Dr. Lawrence A. Tabak, the Principal Deputy Director of the National Institutes of Health (NIH). I am honored to attend this hearing with my HHS Operating Division colleagues to offer NIH’s technical assistance on bills that are currently being considered by the Health Subcommittee.
I have been Principal Deputy Director of NIH for less than a month, but I have led the National Institute of Dental and Craniofacial Research for the past ten years and served as NIH Acting Deputy Director in 2008-09. Before joining NIH, I was the Senior Associate Dean for Research and Professor of Dentistry and Biochemistry & Biophysics in the School of Medicine and Dentistry at the University of Rochester in New York State. I have also been an NIH-funded investigator, working in the field of biochemistry to learn how some proteins become decorated with specific types of sugars and determine the roles played by these sugars. In my NIH lab, my team and I have continued to work on these questions.
It is a privilege to represent NIH before you this afternoon. Because of the support of members of this Subcommittee, NIH is a multidisciplinary powerhouse of discovery and innovation. Nearly 85% of NIH’s $31 billion FY 2010 budget is dedicated to research grants that involve approximately 325,000 research personnel at some 3,000 institutions in each of the 50 states.
We appreciate the opportunity to discuss issues relating to legislation pending before this Committee today. We recognize that you have dedicated time and resources to incorporating our technical input, and we thank you for that.
About the National Institutes of Health
NIH and its research partners—patients and their families, scientists and their research institutions—have collaborated to produce scientific understanding and medical innovation that have prolonged lives, reduced human suffering and improved the quality of life for millions. Due in part to NIH research, mortality from heart disease and stroke has been cut by more than half in the U.S. Today’s new cancer therapies arrest the disease and prolong human life so cancer survivors number in the millions. Our blood supply is far safer because of tests for HIV and hepatitis B and C that arose from NIH-funded research. NIH-funded science has also helped people make lifestyle changes that promote health, such as eating less fat, exercising more, and quitting smoking. These few examples of NIH-funded discovery and medical innovation have transformed medical care.
Whereas a generation or two ago, much of medicine was palliative care for acute and lethal diseases, today we are able to manage formerly fatal disorders as chronic illnesses. In the balance of my testimony, I would like to discuss how the support of Congress has allowed NIH the scientific flexibility to pursue these advances, how we will benefit from today’s scientific opportunities, with that continued support and flexibility and how we are pursuing research initiatives that address conditions mentioned in the bills pending before the Subcommittee.
Congressional Support, Allowing NIH Scientific Flexibility Equals NIH Success
Support for biomedical research—and the hope of new diagnostics, therapies, and cures—is among Americans’ strongest shared values. NIH owes much of its success to the advocacy and strong support of millions of patients and their families.
Historically NIH has also been championed by Congress, and received strong, bipartisan support. As a community, researchers on the NIH campus and around the country are grateful for such support—and mindful of the responsibility we bear to be good stewards of the taxpayers’ investment in medical science.
NIH has also been given the flexibility—and indeed the explicit responsibility—to exercise the scientific community’s best collective judgment in determining research priorities. These decisions are made in a dynamic, continually shifting matrix of scientific opportunity, public health needs, burdens of disease, and the input, consultation, insight and perspective offered by patients and their families, scientists, and public health experts and patient advocates.
The opportunities we see in today’s multi- and interdisciplinary research and NIH’s trans-institute research initiatives are a further affirmation of scientific flexibility in guiding our nation’s biomedical research portfolio. Science today is a far more collaborative, multi-disciplinary and large-scale enterprise than when I was a newly appointed Assistant Professor.
With the investment of the American people and the support of Congress, we have amplified the power of the molecular approach to health and disease over the past couple of decades and sparked a revolution in medicine. Advances in research technologies, such as high-throughput screening and dramatic new imaging techniques, have further accelerated this transformation. As NIH Director Francis Collins has put it:
The revolution now sweeping the field is the ability to be comprehensive—for example, to define all of the genes of the human or a model organism, all of the human proteins and their structures, all of the common variations in the genome, all of the major pathways for signal transduction in the cell, all of the patterns of gene expression in the brain, all of the steps involved in early development, or all of the components of the immune system. Further development of technologies in areas such as DNA sequencing, imaging, nanotechnology, proteomics, metabolomics, small-molecule screening, and RNA interference are ripe for aggressive investment.
This technological revolution and the continuing need for interdisciplinary approaches have blurred the scientific boundaries among traditional scientific disciplines. On June 15, Dr. Collins testified before you about the Human Genome Project, the Cancer Genome Atlas, and the Alzheimer's Disease Neuroimaging Initiative. These are the exciting new initiatives that are possible at this unique moment in our scientific and medical history, and promise new ways of understanding human biology and new hope for prevention, therapies, and cures. The scientific, medical and technological revolutions of today offer the possibility that we can now understand a disease comprehensively and raise the hope that we will be able to diagnose, prevent and ultimately treat many diseases—even tailoring a therapy for a patient based upon her unique genetic makeup. In our era, the era of molecular medicine, we are pursuing advances in myriad diseases as scientific opportunity and public health need dictate.
I would like to offer a few principles that govern NIH research priority setting.
How NIH Sets Priorities
First and foremost, NIH must respond to public health needs which are addressed through a complex balance between basic, transformative, and clinical sciences. The incidence, severity, cost and sheer human suffering associated with specific disorders are also factors in how we set research priorities.
Secondly, NIH applies stringent review, provided by outside scientists who are experts in a given field, in ranking the scientific opportunity and quality of all research proposals considered. The rigor of this process is so competitive, and the number of applications is so large, that today fewer than one in five research proposals receives NIH funding. Even in the past, no more than one in three applications received NIH support. This intense competition has always assured that NIH research is of the highest scientific quality.
Thirdly, scientific history has repeatedly demonstrated that significant scientific advances occur when new findings, often completely unexpected, open up new experimental possibilities and pathways. We are constantly assessing the research portfolio in light of what the latest science suggests. Frustratingly, not all disease or scientific problems are equally ripe for new advances, nor do such advances come at the same rate across the portfolio, no matter how pressing they might be for the public’s health.
Finally, we strive to ensure the diversity of NIH’s research portfolio. We simply cannot predict the next scientific revelation or anticipate the next opportunity. If you think of scientific priority-setting as an innumerable number of questions that we might try to answer, a series of doors that we might open—but we cannot know what is behind any one door—you can appreciate the challenge of setting priorities and the need for a broad research portfolio.
NIH Research Activities Relevant to Pending Legislation:
Having discussed how NIH sets research priorities, I would like to review some of the research we are currently conducting in several of the disease areas that are addressed by the bills pending before the Subcommittee.
Juvenile Idiopathic Arthritis
We know arthritis as a group of diseases that cause pain, swelling, stiffness, and loss of motion in the joints. Juvenile idiopathic arthritis (JIA) is a type of arthritis with no definitive cause and which strikes children before they turn 16.
There are multiple types of JIA that collectively are the most prevalent pediatric rheumatic illness, and among the most common causes of childhood disability in the United States. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) funds a broad range of research, from basic studies of the underlying mechanisms of arthritis, to clinical studies exploring new treatment options.
For example, the NIAMS supports scientists in a network of pediatric clinical research centers, known as the Childhood Arthritis and Rheumatology Research Alliance (CARRA). One NIAMS-supported project is a clinical trial examining the effect of early, aggressive therapy on polyarticular juvenile idiopathic arthritis (poly-JIA), a condition in which five or more joints are affected. This research focuses on the identification and testing of new combinations of drugs not previously tested in pediatric patients.
In other research supported by the NIAMS, investigators have examined the challenges associated with diagnosing the various subtypes of JIA, in hopes of eventually allowing pediatric rheumatologists to tailor personalized treatments.
NIH also recently used funds provided by the American Recovery and Reinvestment Act (ARRA) to support a Grand Opportunities (GO) grant to expand the existing CARRA network and improve the outcomes and quality of life for all children with rheumatic diseases, including JIA.
These research endeavors are just a few examples of the many NIH programs that share the goals of H.R. 1210, the “Arthritis Prevention, Control, and Cure Act of 2010.” The NIH is committed to supporting research that seeks to improve the outcomes and quality of life for children with rheumatic disease.
Scleroderma is a group of diseases in which the connective tissue that supports the skin and internal organs grows in a highly abnormal manner. In milder forms of scleroderma, this abnormal growth causes hard and tight skin in the patient. In other forms of scleroderma, however, the problems are much more serious, affecting blood vessels and internal organs, such as the heart, lungs, and kidneys.
To identify the genetic changes that make an individual susceptible to scleroderma and provide a source of genetic material for researchers who study scleroderma and other autoimmune diseases, NIAMS has supported the Scleroderma Family Registry and DNA Repository. The Family Registry has enrolled approximately 4,000 participants. The information collected allows researchers to conduct genome-wide association studies (GWAS) of scleroderma which will provide insights into what genes are responsible for susceptibility to scleroderma, and which biological pathways may cause organ damage in the disease.
The NIAMS also supports the Center for Research Translation in Scleroderma that is examining the molecular basis of scleroderma in order to understand its underlying causes. Investigators have already conducted detailed genetic analysis of blood samples from scleroderma patients, grouping them by ethnicity, gender, and autoantibodies—the immune system molecules that mistakenly attack the body they would normally protect from infection. In a promising step forward, this research has established the correlation of individual gene variants and disease subtype-specific autoantibodies. Such findings offer the hope of new and personalized treatment options for patients.
NIAMS funds a broad range of research, from basic studies to translational clinical efforts. We share the hope for improved outcomes for scleroderma patients that are conveyed in H.R. 2408, the “Scleroderma Research and Awareness Act.”
Diabetes research in minority populations
There are three main types of diabetes: type 1, type 2, and gestational diabetes. Type 1 is an autoimmune disease where the immune system attacks and destroys the insulin-producing beta cells in the pancreas. The pancreas then produces little or no insulin. Type 2 is the most common form of diabetes and is most often associated with older age, obesity, family history of diabetes, previous history of gestational diabetes, physical inactivity, and certain ethnicities. Finally, some women develop gestational diabetes late in pregnancy. Although this form of diabetes usually disappears after the birth of the baby, women who have had gestational diabetes have a 40 to 60 percent chance of developing diabetes (mostly type 2) within 5 to 10 years.
The NIH, primarily through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), is investing significant resources in multifaceted research on type 2 diabetes in minority populations, as well as in obesity research. Obesity is a major risk factor for type 2 diabetes. Both disorders disproportionately affect minority populations. As part of the NIDDK-CDC National Diabetes Education Program, specific work groups address minority issues and include minority health professionals. The Work Groups include the African American/African Ancestry Work Group, the American Indian and Alaska Native Work Group, the Asian American and Pacific Islander Work Group, and the Hispanic/Latino Work Group. The Diabetes Mellitus Interagency Coordinating Committee, led by the NIDDK, effectively coordinates diabetes activities across the Government, including diabetes issues in minority populations, through regular meetings, strategic planning, development and coordination of special programs, and through evaluation of ongoing diabetes efforts. The DMICC continues to improve the dissemination of information about diabetes and enhance coordination of federal efforts to advance diabetes research and improve the health of Americans with or at risk for diabetes.
Title I of H.R. 1995, the “Eliminating Disparities in Diabetes Prevention Access and Care Act,” aims to increase research in diabetes disparities, as well as participation of health providers from minority communities in this research. While the NIH is making great strides in our efforts to understand and address diabetes health disparities, we continually monitor the state of the science for new and important research opportunities that merit pursuit.
Children deserve to be born healthy and to achieve their full potential for healthy and productive lives, free from disease or disability. NIH, led by the National Institute of Child Health and Human Development (NICHD), supports the bulk of research on normal and abnormal child health and development. The majority of the NIH’s 27 Institutes and Centers (ICs) include pediatric research in their portfolios.
In FY 2009, the NIH, through 22 Institutes and Centers (ICs), awarded about $3 billion in support of pediatric research activities across the country with another $500 million for pediatric research from funding under ARRA. This funding was distributed to the research community through the full range of available funding mechanisms, including investigator-initiated grants, contracts, and research networks, which allowed those with extensive scientific expertise at the NIH and across the extramural scientific research community to determine which mechanism(s) might be best suited for the specific research needed to answer questions about children’s health and development, diseases and conditions. Less commonly, where the scientific challenge warrants and with mindfulness of the significant ongoing investment involved, NIH ICs (often in trans-institute collaboration) have created multidisciplinary centers of excellence or research networks for specific pediatric populations or conditions, such as autism, pediatric oncology, neonatology, and adolescents with HIV/AIDS, to name a few.
In addition, a number of the Clinical and Translational Science Awards (CTSAs) sites include a strong emphasis on creating infrastructure to conduct pediatric clinical trials, which will allow pediatric researchers who focus on a wide variety of conditions to utilize this new resource and to conduct clinical trials efficiently and effectively.
H.R. 758, the “Pediatric Research Consortia Establishment Act”, would require NIH to establish new pediatric research consortia to supplement ongoing research in these areas. We are constantly looking for new ways to push our pediatric research agenda to the next level, and appreciate the interest in exploring this area.
These are but a few of the examples in which NIH is exploring the scientific areas under consideration by the Subcommittee today. Let me conclude my testimony by offering the thanks of NIH, the biomedical research community and millions of American patients and their families for your unwavering dedication. I am personally grateful for your time and attention this afternoon and look forward to your questions.
 “Opportunities for Research and NIH,” Science, January 1, 2010.
 Centers for Disease Control and Prevention (2007). National Diabetes Fact Sheet, 2007. Accessed from http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf on August 31, 2010.
Last revised: June 18, 2013