greater challenge than the CF effort because diabetes is actually several distinct diseases. It would also appear that each form of diabetes arises in the context of a unique combination of multiple gene defects rather than a single gene defect.

It is well established that insulin-dependent diabetes (IDDM) is associated with genes in a specific area of the genome called the HLA locus. There is evidence that in some populations, a specific single letter of the genetic code in this locus is highly correlated with diabetes susceptibility. Studies in animal models of IDDM have suggested that several other genes may be involved with this disease as well. Non-insulin dependent diabetes (NIDDM) shows a strong hereditary pattern which indicates the existence of a significant genetic component to this form of diabetes as well. We are less certain of the basic underlying causes of NIDDM which likely include the interaction of defects in several metabolic processes. Therefore, the specific identification of genes for this disease may require complex and sophisticated analyses that will push the frontiers of our technology.

Recently, the Institute has taken specific action to stimulate research in the areas of genetics, molecular biology and immunology. The process began with colloquia designed to bring together basic scientists with diabetes researchers. The Institute now has begun to receive interdisciplinary research proposals as a result of these colloquia. Workshops and conferences have also been held to highlight and characterize racial/ethnic groups with high rates of diabetes (i.e., Blacks, Hispanics and Native Americans) that may be important populations in which to look for relevant genes.

NUTRITION GUIDELINES

Question. Dr. Gorden, the press has reported the recent publication of the Tenth Edition of the Recommended Dietary Allowances. Can you tell us how the new edition will aid nutrition research and describe the role your Institute played in this effort?

Answer. The Recommended Dietary Allowances (RDAs) are a principal guide for developing nutrition programs and policies and are periodically adjusted to reflect the increasing scientific understanding of human nutrition. For nearly half a century, at the Federal government's request, the National Research Council of the National Academy of Sciences has conducted periodic reviews of the essential vitamins and minerals in the diet. The first RDAs were published in 1941 as a guide for meeting the dietary needs of U.S. troops during World War II. Since then, their use has been expanded by various groups to help provide nutritional guidance for healthy persons. For example, the U.S. Department of Agriculture uses the RDAs to evaluate the adequacy of the U.S. food supply, to establish standards for food assistance programs, and to determine the nutritional status of the U.S. population. The Food and Drug Administration used the seventh edition of the RDAs to derive its U.S. Recommended Daily Allowances, which help set standards that guide how the nutritional content of foods is listed on product labels. Another use of these guidelines is to aid in the development of new food products. From a research point of view,

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when conducting nutrition studies, the RDAs provide a reference or standard against which adequate nutrient intake or nutrient deficiencies can be measured. The National Institute of Diabetes and Digestive and Kidney Diseases has supported the development of the Recommended Dietary Allowances for more than 25 years. The effort to produce the tenth edition was supported under contract by the NIDDK.

INTERSTITIAL CYSTITIS

Question: Why were only two interstitial cystitis (CF) projects approved under the RFA issued specifically for that purpose and for which you had designated $800,000?

Answer: In FY 1989, the NIDDK funded two research grants as a result of its research solicitation on interstitial cystitis (CF) entitled "Request for Applications (RFA) on the Role of Inflammatory Mediators in the Initiation and Maintenance of Chronic Interstitial Cystitis of the Urinary Bladder." We think it is important to look at this RFA in the context of the current NIDDK portfolio of research on IC, which totaled approximately $1.8 million in FY 1989 for 10 regular research grants and one pilot data base. This portfolio represents an impressive growth rate achieved over a very short period of time. In FY 1986, there was virtually no research at all being conducted on IC.

With respect to funding in FY 1989, the NIDDK expended approximately $600 thousand in new funds on IC. The Institute funded two grants from the RFA, as well as one grant through the regular grant application process, and one grant to an existing George O'Brien Kidney and Urologic Diseases Research Center to establish a pilot data base on IC. This represented about a 50 percent increase over the FY 1988 funding level for IC.

Regarding your specific question about the RFA, the NIDDK received 15 research grant applications in response to this research solicitation. The special group of non-governmental scientific experts convened to review and evaluate these applications assigned them numerical scores, based on scientific merit and technical feasibility, that ranged from a low of 163 (the best score) to a high of 473 (the worst score). One application was disapproved.

In the RFA, the NIDDK indicated its intent to expend up to $850 thousand on scientifically meritorious grants resulting from the solicitation. However, given the scientific-merit scores assigned to the resulting applications, the NIDDK was able to fund only two grants from this RFA. The quality of the other applications did not place them within the Institute's fundable

range.

We have tried to underscore to the research community that dollar amounts published in RFAs are "targets" and not absolute funding "set-asides." The driving force behind NIH and NIDDK funding decisions remains the scientific merit of the research grant applications, because our common goal must be to build a high-quality and productive research program on IC.

Question: Do you have plans for any further RFAs?

Answer: To date, the NIDDK has published three RFAs on IC: two for biomedical research grant applications and one for a pilot IC data base. In addition, the NIDDK has sponsored conferences and workshops to encourage investigators to pursue this field, and has published a "Program Announcement,' a general type of research solicitation, with the same objective. Encouraging research on IC is a high priority of the NIDDK, which welcomes research grant applications in this area. During 1989, the Institute's Kidney, Urologic and Hematologic Diseases published Requests for Applications in only two disease areas, and one of these was IC. The Institute will continue to publish Program Announcements on IC each fiscal year, and will publish RFAs periodically, to pursue emerging research leads suggested by ongoing studies, as well as by conferences and workshops. The Institute submitted a five-year plan for research efforts on IC to the Appropriations Committees in 1989.

Question: When do you plan to issue an RFP for the IC National Registry?

Answer: The NIDDK has carefully considered the possibility of establishing a national registry on IC, as requested by the Congress. The Institute has concluded, however, that it would be most appropriate to test the usefulness of the newly developed diagnostic criteria before pursuing the concept of a national IC registry. In its five-year plan for IC, submitted to the Congress in April 1989, the Institute outlined the advantages of establishing a pilot IC data base, rather than a national registry, at this point in time. The most important consideration is that IC remains a disease with widely varying symptoms. Thus, for research purposes, it is important to begin to collect data in a "pilot" mode on a well-defined group of patients who share similar characteristics, based on the preliminary set of diagnostic criteria which the NIDDK has developed in conjunction with the IC research and IC voluntary health communities. Such a pilot data base offers the most promising opportunities for finding clues about the causes of IC in these patients, and it also provides a well-defined group of patients for possible future clinical studies and trials. In contrast, given the current state of knowledge about IC, the NIDDK believes that it would be scientifically premature to set up a national registry for IC patients, for whom clinical data could be expected to be extremely variable. In FY 1989, the Institute made a grant award to an existing George O'Brien Kidney and Urologic Diseases Research Center to establish a pilot IC data base.

NEGOTIATED REDUCTIONS

Question. Dr. Gorden, I understand that the cost of biomedical research outpaces the inflation rate by approximately 2 percent. How do you account for this dynamic? Given the fact the Institute's budget rises only 4% over 1990, what impact will this have on the Institute's activities in fiscal year 1991?

Answer. In order to maintain approximately the same total number of research project grants and centers we have had to

negotiate reductions from the Study Section approved funding levels for each grant and center.

Question. What will the Institute's downward negotiation rate on research project grants and center grants be in FY'91? How does this compare to fiscal years 89 and 90?

Answer. For research project grants, we will be making cuts of 11% in 1991. This compares to cuts of 11% in 1989 and 12% in 1990. Centers will be cut 30% in 1991 compared to 21% in 1989 and 25% in 1990.

RARE METABOLIC DISEASES

Question. Dr. Gorden, I understand that many children within Amish and Mennonite communities are afflicted with rare metabolic diseases, such as glutaric aciduria. I further understand that many of these disorders may be treatable through early detection and changes in diet. To what extent is the Institute aware of these problems and the potential treatments? Has the Institute approved any grants in this area research? If so, were there sufficient funds to support the grant or grants?

Answer. This Institute is well aware of the rare genetic metabolic diseases such as glutaric aciduria which afflicted the Amish and Mennonite communities. The two distinct types of glutaric acidurias are complex and heterogeneous diseases. There are very early onset forms which result in death during the neonatal period, as well as later onset cases which may also cause sudden death. A connection between glutaric aciduria and sudden infant death syndrome is presently being investigated. One variant of the disease responds to dietary supplementation by riboflavin, which is a component of the vitamin B complex. The NIDDK supports three research programs which explore the diagnosis, molecular biology, pathophysiology and treatment of the disease. This support amounted to a total of $550,903 during FY 1989.

NIDDK also supports research in another rare genetic metabolic disease which afflicts the Amish and Mennonite communities, namely, Maple Syrup Urine Disease (MSUD). This disease, which is due to an enzymatic defect and is also heterogeneous, develops during early childhood and causes mental retardation and ultimately death. Dietary intervention, by control of the protein intake especially the amino acids valine and leucine, is an accepted therapeutic approach for this disease. The NIDDK supports five research projects which explore the diagnosis, the molecular and genetic basis and therapeutic approaches to MSUD and totaled $921,716 during FY 1989. The NIDDK, in collaboration with the NICHD, has recently issued a Request for Applications on "Nutritional Therapy for Inborn Efforts of Metabolism.

NATIONAL INSTITUTE OF CHILD Health and HUMAN DEVELOPMENT

STATEMENT OF DR. DUANE ALEXANDER, DIRECTOR

SUMMARY STATEMENT

Senator HARKIN. Now we will go to Dr. Alexander, and the National Institute of Child Health and Human Development.

Dr. Alexander, your budget request is $461.47 million for a 4.19percent increase.

Welcome and please proceed.

PROGRAM PRIORITIES

Dr. ALEXANDER. Thank you, Mr. Chairman. The research program of the NICHD cuts across age and disease categories and encompasses the study of normal as well as abnormal development. The broad mission of our Institute and the relevance of that mission to some of the most critical public health problems of our time are reflected in the fact that NICHD research addresses 8 of the 10 Public Health Service priorities recently identified by the Assistant Secretary for Health.

These eight priorities include infant mortality, AIDS, strengthening the family, drug and alcohol abuse, improving minority health, enhancing health promotion and disease prevention, environmental and occupational health, and maintaining research capacity.

Senator HARKIN. Excuse me, does drug and alcohol abuse encompass tobacco abuse?

Dr. ALEXANDER. Yes; it does, sir.

Senator HARKIN. Continue on, but I want to ask you more about what you are doing on that.

INFANT MORTALITY

Dr. ALEXANDER. I would be glad to tell you that. Reducing infant mortality is a long-standing national priority. The 1988 rate reached 9.9 deaths per 1,000 live births, the lowest level ever recorded and a substantial reduction from our 1978 rate of 13.8, though still short of the 1990 objective of 9 deaths per 1,000.

Current data indicate that birth defects, sudden infant death syndrome and low-birth weight are the leading causes of death in infants. To reduce this Nation's infant mortality rate, NICHD is placing greater emphasis on research to elucidate their causes.

AIDS RESEARCH

AIDS is an increasing problem among infants, children, and women, and will soon become the fifth leading cause of death for children and young people from birth to 24 years of age. The NICHD's AIDS research program focuses on preventing transmis