Statement of Dr. Phillip Gorden
Director, National Institute of Diabetes and Digestive and Kidney Diseases Mr. Chairman and Members of the Committee:
I am pleased to testify on behalf of the research programs, progress and opportunities of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Our institute has responsibility for the national biomedical research effort to combat some of the most important, chronic diseases in this country, including diabetes, endocrine and metabolic diseases; digestive diseases and nutritional disorders; and diseases of the kidney, urologic tract and blood. These diseases inflict tremendous suffering and health care costs on the American people because they are life-long, debilitating, and often relentless. The President in his FY 2000 budget proposed that the NIDDK receive $1,002.7 million, an increase of $23.4 million (2.4%) over the comparable FY 1999 appropriation. Including the estimated allocation for AIDS, total support proposed for NIDDK is $1,021.1 million, an increase of $23.9 million over the FY 1999 appropriation. Funds for NIDDK efforts in AIDS research are included within the Office of AIDS Research budget request.
The activities of the NIDDK are covered within the NIH-wide Annual Performance Plan required under the Government Performance and Results Act (GPRA). The FY 2000 performance goals and measures for NIH are detailed in this performance plan and are linked to both the budget and the HHS GPRA Strategic Plan which was transmitted to Congress on September 30, 1997. NIH's performance targets in the Plan are partially a function of resource levels requested in the President's Budget and could change based upon final Congressional Appropriations action. NIH looks forward to Congress' feedback on the usefulness of its Performance Plan, as well as to working with Congress on achieving the NIH goals laid out in this Plan.
As the Nation turns the page to the 21st century, the NIDDK will be celebrating its 50th anniversary. Thus, it is a time for both reflecting upon the Institute's accomplishments and looking forward to the promise of future research advances. In this vein I would like to strike two important themes. The first is to emphasize our clinical advances and their special relevance to the treatment and prevention of disease. The second is to underscore the vital basic science discoveries that create the technology that drives these advances. Both aspects of research are critically important and must be strongly supported and nurtured.
Clinical Advances and Their Special Relevance to the Treatment and Prevention of Disease
A major multicenter, large-scale clinical trial in patients with type 2 diabetes has clearly demonstrated the efficacy of good blood sugar control in ameliorating the microvascular eye, kidney, and nerve complications. This study is an important confirmation of the NIDDK's major Diabetes Control and Complications Trial, which demonstrated similar benefits in type 1 diabetes. In addition, the recently completed type 2 trial demonstrated that good blood pressure control produced a major benefit in decreasing macro vascular events such as stroke. These findings give new emphasis to the value of early treatment in type 2 diabetes. They also reinforce the importance of our Diabetes Prevention Program, a major clinical trial for which recruitment is almost complete. This trial focuses on adding a prevention strategy to existing therapeutic approaches. It is especially addressed to our minority populations who are disproportionately affected by type 2 diabetes.
Previously, we considered end stage renal disease to be an inexorable consequence of severe kidney complications of diabetes. Recent studies now show that the type of long-term glucose control that can be accomplished by pancreas transplantation can actually lead, over a long period of time, to a reversal of these complications. These remarkable findings have revolutionized our clinical thinking about the progression of the kidney complications of diabetes and have reinforced the importance of glucose control as demonstrated in other studies.
Advances in producing immune tolerance to enable transplant recipients to accept and retain donated organs and tissue have given new emphasis to the field of transplantation and its role in the treatment of diabetes and end-stage renal disease. To capitalize on these achievements, we are investing in a new intramural effort focusing on both kidney transplantation and pancreatic islet cell transplantation. We are also pursuing a major multi-institution initiative in islet cell transplantation. These endeavors are an excellent example of how NIDDK program development is shaped by emerging scientific opportunities that are created by technology development.
In hepatitis C, the NIDDK intramural program carried out the initial studies demonstrating the therapeutic efficacy of alpha interferon. This advance was possible because of fundamental studies showing that this type of agent could inhibit viral replication and because of biotechnology advances permitting the manufacture of such compounds. These studies spurred further drug development and a more profound understanding of the nature of the hepatitis C virus. As a result, we now have a new combination therapy using alpha interferon and another anti-viral agent, ribavirin. Used together, these drugs lead to long-term remission of hepatitis C infection in up to 40 percent of individuals. Furthermore, using knowledge about the various subtypes of viruses that lead to this disease, we can tailor this therapeutic strategy more effectively to individual patients. These developments constitute a significant therapeutic advance in a disease that affects over four million Americans and is the leading cause of end-stage liver disease.
For the debilitating bone disease, osteoporosis, we have introduced a number of therapeutic strategies founded on basic research and made possible by the technology revolution. During the past year, researchers have demonstrated that parathyroid hormone, an important regulator of bone metabolism, has an important beneficial effect in increasing bone density. This research adds another impressive clinical tool to the treatment and understanding of osteoporosis.
Important Basic Discoveries Create Technologies that Drive Clinical Advances
In obesity research, the initial discovery of the major energy regulator, leptin, in a mouse model of obesity led to the discovery in rodents of multiple gene mutations, which control critical aspects of both eating and energy regulation. These findings have now led to the discovery of at least five different genetic defects in humans that lead to obesity. These important research advances have relevance not only to our understanding of obesity per se, but also to the inter-relationship of obesity and diabetes.
While leptin itself may not prove to be a major therapy for obesity, it has clearly led us in directions that are likely to produce major therapeutic progress. In addition, these discoveries have infused our obesity research portfolio with innovative ideas for further understanding of the molecular basis of obesity. This research, in turn, is expected to reveal new therapeutic targets. For example, we are making a substantial investment in a multi-center clinical trial to demonstrate the health benefits of long-term, voluntary weight loss. This clinical trial will be conducted in obese patients with type 2 diabetes. In this way, we will test both lifestyle and drug strategies highly relevant to both obesity and diabetes.
In addition, our major investment in genetic and functional genomics research has led to the discovery of at least six separate genetic defects in rare forms of type 2 diabetes. These studies have stimulated collaborative research to penetrate the complexity of genetic abnormalities in both type 1 and type 2 diabetes. Expansion of these studies is now under way, with an emphasis on the kidney complications of diabetes. Thus, we are now making a major commitment to a large-scale study of the genetics of diabetes per se and the genetic susceptibility to diabetic renal disease.
Ground-breaking discoveries of genes that cause cystic fibrosis, polycystic kidney disease, and hemochromatosis are leading to investments to an understanding of the functions of these genes. These discoveries give us the opportunity to develop screening strategies for early intervention in the iron-overload syndromes, such as hemochromatosis. They likewise provide promising opportunities to discover new therapeutic strategies for other liver diseases, Cooley's anemia, and neurodegenerative diseases.
Our endocrine program has provided the basis for understanding the development of designer-type drugs, such as estrogen compounds. Technology has enabled researchers to devise novel drugs, which have specific beneficial effects on certain tissues, such as bone, and do not carry the adverse effects on breast and uterus seen in the more classic estrogen preparations. We are now beginning to understand the basis for this type of tissue specificity, which affords us the opportunity to use knowledge derived from basic research to develop clinical approaches to endocrine-responsive cancers, such as prostate and breast cancer.
Infrastructure Development
To sustain and enhance these clinical advances, and the fundamental science that drives the technologic applications from which they flow, it is imperative that we maintain a strong infrastructure of support. The first and perhaps most important component of the research enterprise is "human infrastructure." We are renewing our efforts to strengthen research training and career development to ensure that we have the cadre of talented scientists needed for the 21st century. We are encouraging and participating in the NIH-wide effort to bolster the recruitment and training of modern-day clinical investigators. We are also making a major investment in biotechnology centers in an attempt to use the most modern approaches to both gene discovery and its application to gene function and to therapeutic advancement. Complementing these activities are NIDDK's participation in trans-NIH infrastructure initiatives such as the zebrafish and mouse genome efforts to provide critical research resources to investigators.
Other examples abound demonstrating that an insight gained from undifferentiated, technology-based laboratory research is often transformed into a clinical stride forward, with widespread application to various disease processes. For instance, the generation of new knowledge about the physiology of erectile function has helped pave the way to the development of agents such as Viagra. Another example is the use of modern technology to develop antibody treatment for refractory Crohn's disease, and to gain insights into processes that are implicated in areas of women's urogolic health such as interstitial cystitis and incontinence.
Genetic engineering techniques enabled the production of synthetic human erythropoietin, a hormone useful in treating the anemia of end-stage renal disease and other conditions. Most recent studies have shown that a modified form of erythropoietin, linking two molecules together, can create a more potent drug with a longer half-life. With this new approach, it is possible to reduce the cost of this treatment while maintaining its efficacy.
We are also able to conceptualize totally new and promising strategies based on a more profound understanding of underlying disease processes. Because of clinical studies made possible by high-technology basic research, we are developing new prevention strategies to fight disease. For example, both animal and human studies of type 1 diabetes demonstrate a shift from beneficial to destructive inflammatory mediators of the immune system called cytokines. With this knowledge, we are formulating innovative, prevention-oriented approaches, including the development of special reagents aimed at interdicting this process.
Modern technology lets us visualize disease at the molecular level; measure and assess biologic events in amazingly precise ways; develop therapies that are site-specific; and test hypotheses in sophisticated model systems. The application of these technologies to basic research questions in the laboratory is often the critical first step to combating disease.
At the threshold to the 21st century, we are on the brink of enormous clinical progress. In some diseases areas, we sense extraordinary research momentum propelling us forward toward major medical advances. In other areas, we are still at an "interface" between an important, clinically-relevant finding that augurs eventual application to the practice of medicine. In still others, much more basic research needs to be done before clinical insights can surface. In every field, however, the technology revolution is moving basic research forward into the clinical arena at an unprecedented and truly exciting pace.
