Answer. In recent years we have vastly expanded our understanding of the pathogenesis of CF and at the same time improved the length and quality of life of patients afflicted with CF. We need to expand on this progress to develop effective therapy targeted at the basic defect in CF. Both gene therapy and pharmacologic therapies offer promise in this regard. Several of our investigators, as well as a member of our National Advisory Council, have expressed interest in the establishment of gene therapy centers, in which cystic fibrosis research would be a

cornertone.

Because so much progress in CF has resulted from the application of advances in basic molecular and cell biology to understanding CF, I believe it is essential to provide adequate support for this basic research. Thus NIDDK is supporting research directly aimed at developing techniques for gene therapy in CF and also a broader array of projects to resolve obstacles to progress in gene therapy. Many questions remain about molecular mechanisms of normal and aberrant chloride transport characteristic of CF. Elucidation at the molecular level of the structure and function of elements of membrane transport systems offers the key to rational drug design targeted at the basic defect.

KIDNEY INITIATIVES AND ADVANCES

Question. Over 13 million Americans suffer from various kidney diseases and last year over 250,000 people died from kidney and related diseases. Kidney diseases are among the nation's most acute and growing public health problems. As a result the Congress encouraged the NIDDK to place a special priority on research initiatives investigation in the area of kidney and related diseases. Can you tell me what has been done in response to Congress' request? What is being done at improving the understanding and treatment of kidney diseases?

Answer. There have been NIDDK initiatives in the areas of End-Stage Renal Disease, Progression in Kidney Disease, and Basic Research in Kidney Disease. The initiative directed at the causes of dialysis morbidity and mortality is the newest activity. The initial work was the development of a database on which to develop the appropriate research strategies. This resource is called the United States Renal Data System. The second is to evaluate dialysis and transplantation technologies since the mortality rate for hemodialysis patients remains at nearly 20 percent annually, an unacceptably high rate. In addition, fewer than 60 percent of renal transplants are functioning five years after placement; and the patients must return to dialysis or receive another transplant. For these reasons, a five-year research research plan was developed which begins with a consensus meeting on dialysis therapy in FY 1992. This will be followed by a research solicitation.

A group of clinically relevant studies are directed at the intervention, or slowing, of renal disease progression to complete renal failure. Two studies are directed at the control of blood pressure in diabetics, and one addresses the efficacy of controlling dietary protein intake and blood pressure. group of clinical studies are the effect of the strict control of blood glucose on the development of kidney disease in juvenile

A third

diabetics and the natural history of diabetes mellitus in the Native American population (Pima Indians).

Finally, we are pursuing an active basic research program into the causes and consequences of renal diseases, including polycystic kidney disease, kidney disease of diabetes mellitus, genetic kidney diseases, hypertension and kidney disease in minorities, and acute renal failure due to toxic or circulatory injuries.

RECOMMENDATION OF THE NATIONAL KIDNEY AND UROLOGIC DISEASES
ADVISORY BOARD

Question. Last year over 250,000 people died from kidney and related diseases. In your professional opinion, to increase funding for kidney disease funding, how much would be necessary? How would that money be spent?

Answer. The National Kidney and Urologic Diseases Advisory Board recommended the following: (1) Increase NRSA funds by $8 million annually, (2) Increase Career Development Awards by $5 million annually, (3) Increase the Research Grant Budget by $46 million annually, (4) Increase the number of George O'Brien research centers to 18, costing $15 million annually, and (5) Increase the effort in clinical trials research, costing $20 million annually.

GEORGE O'BRIEN KIDNEY CENTERS

Question. The NIDDK currently supports six George O'Brien Kidney and Urology Research Centers. In 1991, the NIDDK established a multidisciplinary Research Center of Excellence in Pediatric Nephrology and Urology. At the current time do existing research opportunities warrant new centers, and if so, in what areas would the NIDDK focus research efforts on?

Answer. There is a major need to extend and expand research into the basic causes of prostate diseases. At the present time prostate diseases account for the most common causes of surgical intervention in adult males, and the incidence continues to increase as the population ages. Minority populations are at substantially increased risk for prostate diseases. For these reasons research on the basic aspects of prostate growth and function is imperative. There is now only one center dedicated to research on prostate diseases. In that center there have been several significant research advances made over its short three year history. These include the isolation of a factor in the fluid derived from the testis that promotes excess prostate growth, and the isolation of the cellular elements of the prostate and ability to grow them in culture so that further studies can be quickly · done. This demonstrates that the state of the basic science knowledge and expertise is now at a state that significant new advances can be made if new research centers on prostate were to be initiated. The American Urology Association has recognized this need, as well, and has this as its top priority for the next few years.

INFLAMMATORY BOWEL DISEASE

Question. Last year the Committee added $2,000,000 for research in inflammatory bowel disease--Crohn's disease and ulcerative colitis. What activities have been supported with this additional funding?

Inflammatory bowel disease (IBD) research has benefited greatly from the infusion of the funds which the Committee provided. With this assistance, the division was able to provide additional support to several of our Digestive Diseases Centers, which conduct IBD research. Among new research projects submitted during FY 1991, we were able to fund three outstanding grants. addition, we were able to fund several investigators whose applications had received excellent priority scores but were not in the normal fundable range.

Is this an area of research that is "ripe" for further advances if funding were available?

子

In

Last year, the Institute issued a program announcement regarding IBD. The biomedical research community has responded by submitting over 28 research grant (R01) and program project grant (PO1) applications to investigate the etiology and mechanisms of disease in IBD. It is clear from the wide range of topics (from the evaluation of animal models to the genetics of IBD) that many established investigators are willing to focus their research activities in this important area. Thus, intensified and funded research in this area should provide important answers to our understanding and treatment of IBD, which is estimated to affect two million Americans.

Question. Do you have ongoing contact with the Crohn's and Colitis Foundation of America (formerly the National Foundation for Ileitis and Colitis) so that research advances can be communicated to the patient population through newsletters, support groups, and educational programs sponsored by such voluntary health agencies?

Answer. Over the years, the Division of Digestive Diseases and Nutrition (DDDN) has been in the process of building a very cooperative relationship with the Crohn's and Colitis Foundation of America (CCF) (formerly with NFIC). In 1989, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) held a workshop on Inflammatory Bowel Disease (IBD) to discuss the future research agenda. The CCF was invited and many members of that organization presented information which has been used as a blueprint for program planning of the division. In addition, the NIDDK-supported National Digestive Diseases Information Clearinghouse provides a central point for the exchange of information among professional organizations, foundations, and voluntary health organizations involved with digestive diseases, including inflammatory bowel disease. A database of materials produced by voluntary and professional organizations, hospitals, manufacturers, government agencies, and a variety of other sources has been created and is available through the Combined Health Information Database.

FOCUS FOR NUTRITION RESEARCH

Question. It has been stated that five of the 10 leading causes of death have been associated with dietary habits (U.S. Dept. of Health and Human Services, The Surgeon General's Report on Nutrition and Health, 1988). In fact, it is believed that some 30 percent to 60 percent of all cancers may be associated with diet (National Research Council, Diet, Nutrition and Cancer, 1982). Given this close relationship of diet and nutrition to human disease, it is surprising to find that there is no clear focus for nutritional research at NIH. Can you explain why this is the case?

Answer. There is a clear focus for nutrition research provided by the NIH Nutrition Coordinating Committee, which is a catalyst for trans-NIH meetings, conferences, and research solicitations in this field, as well as the mechanism for providing a cross-fertilization and interchange of research activities and plans among the institutes. Primary research activity in nutrition remains at the institute level, consistent with the research orientation of each NIH component. For example, nutrition research as it relates to cancer is funded by the National Cancer Institute. Similarly, nutrition research as it relates to heart disease is funded by the National Heart, Lung and Blood Institute. Fundamental nutrition research in such areas as nutrient metabolism is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. We believe this organizational approach is the most appropriate one for nutrition research. In FY 1992, 15 NIH components will collectively spend approximately $323.2 million on nutrition research.

OBESITY RESEARCH

Question. Obesity appears to figure importantly as one of the chief nutritional disabilities provoking untimely death from diabetes, heart disease and other ailments. The NIH, some years ago, played a central role in pointing out the importance of obesity in a Consensus Conference. Yet, treatment appears to be of uncertain quality and non uniformly helpful. Why has NIH not had an additional Consensus Conference to inform the medical profession and the Ameerican public on what constitutes optimum treatment? Shouldn't the medical profession and American public know whether there is a recommended treatment?

Answer. I'm pleased to tell you that the NIH sponsored a Consensus Development Conference on "Gastrointestinal Surgery for Severe Obesity" on March 25-27, 1991. This conference evaluated the objective data for new surgical procedures developed in the last 10 to 15 years, which use principles of reduction of gastric volume, intestinal malabsorption, or both. Refinements in these procedures have led to reports of successful results superior to those seen with the earlier intestinal bypass operations. In addition, the National Institute of Diabetes and Digestive and Kidney Diseases is in the process of establishing a National Task Force on the Prevention and Treatment of Obesity. Comprised of eminent scientific experts, this Task Force will review the current stateof-the-science from a clinical perspective and develop a consensus about preventive and therapeutic approaches. The Task Force will also identify issues for future clinical study. At the same time,

the NHLBI is exploring the possibility of establishing a new program that would focus on obesity as a risk factor for hypertension. The Nutrition Coordinating Committee is also very active with respect to obesity. It has established a Work Group on Obesity that has met monthly since last June; is planning a major conference on obesity for 1991; developing Requests for Applications, Requests for Proposals, and Program Announcements related to obesity; and focusing special attention on prevention of obesity in its annual report. I think that all of these efforts are contributing to a greater understanding of obesity and its treatment and prevention, and that the American public will benefit as a result.

OBESITY PREVENTION RESEARCH

Question. Isn't there more to nutrition than simply cajoling people to eat a different diet? Is there no scientific base that can be generated by clinical investigation which will determine how diseases such as obesity can be prevented?

Answer. I agree that we need to have some general guiding principles about the treatment and prevention of obesity and that these principles need to have a sound scientific basis. Developing such principles is one of the major objectives of a new National Task Force on the Prevention and Treatment of Obesity, which the National Institute of Diabetes and Digestive and Kidney Diseases is in the process of establishing.

GENETIC/METABOLIC FACTORS IN NUTRITION

Question. What are the NIH initiatives to bring modern molecular biologic science into nutrition?

Answer. The techniques of modern molecular biology are being applied to nutrition research in many ways. One avenue is the study of genetics in obesity, along with the search for metabolic factors that may regulate the storage of fat at the cellular and molecular levels. The National Institute of Diabetes and Digestive and Kidney Diseases is in the forefront of fundamental research in these areas. Recently, the NIDDK and the NICHD issued a joint solicitation to encourage additional research grants on the genetic and metabolic factors associated with the development of obesity in childhood, adolescence and adulthood. In addition, research efforts would focus on genetic and metabolic factors discernible in childhood that predict the onset of obesity later in life. Applications received in response to this RFA have now received initial review, and pending secondary review, it is expected that several will be funded.

NUTRITION RESEARCH TRAINING

Question. Are there a pool of physicians who are trained to do research in nutrition? Are these physicians learning modern scientific skills in molecular biology?

Answer. Yes, there is such a pool, but it would benefit from expansion. To this end, the National Institute of Diabetes and Digestive and Kidney Diseases has taken the initiative in