Kegular projects

An additional amount of $10,318,000 over the President's budget could eff tively be used to fund very promising projects in the broad attack on corona heart disease, hypertension, and stroke. Of this amount, $3 million would used to initiate new, regular research projects at the same program level as 1966. Other specific programs in the advanced planning stages which wou require approximately $4,300,000 to support, are itemized as follows:

Thrombosis.-Thrombosis, judged by mortality and morbidity statistics, is t largest single health problem of this country. An advance in the understandi of the etiologic factors, pathogenesis, and therapy of this entity would be enormous economic and social importance. Thrombosis is responsible for major proportion of deaths from coronary disease and cerebrovascular disea in the United States and for an enormous cost to the national economy.

Urokinase clinical trial.—Of the fibrinolytic agents, those having the abili to dissolve a blood clot, the enzyme urokinase has been identified as one of t most promising. Preliminary work to test certain properties of urokinase and develop a protocol for a cooperative clinical trial is underway. Additional fun for clinical testing and for purchase of urokinase would amount to $500,000 abo current program costs. Further elaboration of this program is included in t "Highlights of Research Progress" accompanying the statement of the Institu Director.

Nonenzymatic thrombolytics.-The nonenzymatic approach to the problem thrombolysis is another area of prime interest to the Heart Institute. Hi priority has been given to work on the induction of fibrinolysis and thromboly by chemical compounds that are not enzymes. Preliminary investigations a now being conducted with a number of such compounds. It is anticipated th in 1967, expanded clinical trials will get underway; these will require an es mated $500,000 to support. Efforts in this area are being closely coordinat with the other trials associated with the Institute's thrombolytic thera program.

Hemophilia.-The development and investigation of antihemophilic agents w require a close and continuing working relationship between Institute staff, t American Red Cross, and certain pharmaceutical firms. It will also invol the collaboration of a number of clinical investigators who are expert in th field. The immediate steps in 1967 would be to develop antihemophilic globul (AHG) and plasma thromboplastin component (PTC). Increased funds cluded in this proposal would be utilized for this purpose ($1 million).

Blood fractionation.-Basic research has advanced the field of fractionati and component therapy to such a point that whole new areas of treatment thrombotic and hemorrhagic diseases are now possible. Approximately $1 m lion would be used to initiate a major program for complete blood and plas fractionation.

Rheumatic fever.-Though major advances in clinical and laboratory search methods have resulted in greater clarification of the identification a natural course of rheumatic fever, major gaps still exist in knowledge of i pathogenesis. Substantial efforts are critically needed to identify better metho of diagnosis, prevention, and treatment of this disease.

The Institute's planned expansion of this program will utilize approximate $600.000 in support of large-scale epidemiologic and therapeutic studies parti ularly in areas where large numbers of untreated rheumatic fever patients a still available.

Hepatitis after cardiovascular surgery.-Pilot operations for a cooperati study on "the prevention of hepatitis after cardiovascular surgery" have be carefully reviewed, approved, and are being carried out. Further developme of the protocol and other phases of operation would utilize an addition $300.000 in 1967.

Standards, reference materials, etc.-Additional funds of $200,000 would su port the preparation, standardization, and distribution of special biological m terials as reference standards for research workers: examples, mucopolysa charides and synthetic radioactive vasoactive materials (bradykinin, angiote sin).

Antihypertensive and antiarrhythmic drugs.—An additional $200,000 wou support the development and evaluation of these drugs in grant-supporte projects.

Of crucial importance in connection with the above programs, from a pr fessional viewpoint, is the need for the institute to have some ability to modi the allocation of funds appropriated. Modification of budget plans are ofte

necessary during the course of the year to take advantage of program opportunites while simultaneously using the available resources in an economic and efective manner. Flexibility is necessary to utilize either the grant or conTact mechanism when one or the other has been determined as the more expetiricus mechanism for funding Institute programs.

Also included in this proposal for regular projects is an additional $3,018,000 implement cost sharing for indirect costs. This amount would provide for indirect costs at an average approximating 25 percent.

special projects

Categorical clinical research centers.—An additional $2 million is provided for increased hospitalization costs within the programs currently supported by the Istitute. This escalation has resulted from recent policy changes.

Specialized research centers.-The value of initiating a specialized cardiorasular research center program has been presented to the Congress for the jast 2 years and funds for planning grants for this program were included in the supplemental appropriation for heart disease, cancer, and stroke. The ditional $500,000 included in this budget would provide for the necessary Lreases in planning activities.

Heart cooperative drug study.-In both 1965 and 1966 the Congress supported plementation of the cooperative study of drugs and coronary heart disease and this major national clinical trial of lipid lowering agents is now underFar. An additional $2,226,000 would allow this study to proceed in accordance with the carefully developed protocol for this phased program.

B Training grants, difference of $5,147,000

This budget would provide sufficient funds to establish or further develop ardovascular training programs of merit and need. These training programs are of special relevance to the Institute's mission and have been developed with Saf assistance and advice. Failure at this time to expand such training will inevitably limit the entire cardiovascular research program in subsequent years. The Institute is proceeding to initiate a cardiovascular clinical training program, the need for which was emphasized in last year's House report. This program weld train high caliber physicians in those specialized cardiovascular skills which are essential to provide high level care to the public.

2. DIRECT OPERATIONS

4. Collaborative studies, differences of 33 positions and $16,008,000

Of this difference: (1) $200,000 would be programed for statistical processing serves for Biometrics Research Branch to handle the accumulated backlog of Creased data processing requirements; (2) $120,000 would be used for direct cal and statistical coordinating responsibilities related to the cooperative study of drugs and coronary heart disease. This amount supplements the reimbursable agreement with the Communicable Disease Center, Bureau of State Services, which provide the central laboratory services for this study; (3) 827,000 would provide for the operation of the clinical and laboratory examinahot phase of this carefully designed epidemiological study of coronary disease Puerto Rico-pilot operation of this program has allowed the examination of wer 1.000 subjects in 1966-full operation to examine 5,000 subjects in 1967 is pendent upon provision of this increase for this important project which will plement the Framingham operation; (4) $260,000 and 4 positions would provide support for the operational phase of the Hawaii-Japan study of coronary disease and cerebrovascular disease now that all groundwork of organization of this research program has been completed. All examination procedures have en established and tested on approximately 200 subjects. Over 9,500 men of Japanese descent have volunteered to participate in this important study and the desired examinations for 5,000 subjects in 1967 would utilize this increase. In addition $15,168,000 would launch a greatly expanded program of research and development to make totally implantable artificial hearts and artificial

ter heart devices a clinical reality within the shortest time possible. Recent progress in this area has been substantial and the program accomplisheats and future are reviewed in a special report prepared for insertion into the record.

The important difference between this budget proposal and previous proposals ret:

(1) The realization that the NIH must play the role of the central co diation and development office and in assuming this role must create te and evaluation facilities.

(2) The recognition that some additional biomedical research is nece sary which cannot be includued separately under any of the hardware su systems research and development as had been done in previous budgets. Study contracts designed to indicate which direction this program shou take, including budget plans, are now approaching completion. While all of th information is not as yet available, the best professional judgment is that t level of funds that could best be utilized is that indicated herein.

Thus, it is apparent that the contracts and grants programs have alread produced ample returns on the relatively modest investment made in artifici heart development to date. This progress indicates that, in availing itself the vast resources and talents of private industry as well as those of academ research institutions, the artificial heart program will be able to marshal formidable array of research firepower against the problems that still confro us. Recruitment of additional highly skilled personnel is underway for pla ning, coordinating, and administering a program of steadily increasing sco during the years ahead. There is every reason for optimism that, within t next 5 to 10 years, the research investments of the past decade and those st in store will begin to yield dividends in human lives that will make the cost the program seem trivial.

The professional judgment of the amount of funds that could be effective applied to this appropriation exceeds the President's budget by $7,253,000. Th difference would be used as follows:

A. Research, difference of $5,285,000

1. GRANTS

Regular projects, difference of $4,285,000.-This amount would permit suppo of high priority competing research grants approved or expected to be approve by the National Advisory Dental Research Council. This increase would allo more investigations into periodontal disease, congenital anomalies, dental carie dental materials, growth and development, and other areas related to or diseases.

Development (Dental Research Institutes), difference of $1 milion.-Th amount would support developmental grants at selected institutions qualifie to operate extensive research programs under the category of dental researc institutes. These would be at selected university centers, not immediately d pendent upon new construction, which are eminently qualified to receive phased-in type of broadly based research support.

B. Fellowships, difference of $250,000

This amount would provide support under the career development program for approximately 15 individuals who will have completed their formal degreeoriented research training, but who require additional experience to reach the stature of an independent investigator.

C. Training, difference of $727,000

This amount would support 14 new programs for 60 to 80 additional trainees in areas of genetics, epidemiology, pharmacology, and radiology specifically related to dental problems as well as other basic science areas related to dentistry.

2. DIRECT OPERATIONS

A. Direct research, difference of 15 positions and $461,000

Clinical research, increase of $112,000.-This increase would permit the initiation of a longitudinal, morphological, histopathological, and cytological study of the various soft tissue lesions of the mouth including leukoplakia. The most important aspect of this study will be to attempt to correlate the incidence of all types of leukoplakia with those that undergo malignant change. It would also permit us to further exploit the opportunities for utilization of the clinical center patients in such research studies as (a) pulp responses related to restorative procedures, materials, and therapeutic agents; (b) general anesthesia; and (e) osteotomy procedures in the mandible for correction of occlusal abnormalities. Microbiology research, increase of $28,000.-The requested increase would strengthen and expand research in the gnotobiotics area, particularly to exploit the lead afforded by the recent discovery of a specific transmissible periodontal pathosis in hamsters.

Biochemistry research, increase of $53,000.-This increase would permit expansion of studies concerned with the hereditary and environmental factors in Congenital malformations with particular attention to drug metabolism in the fetus and newborn of experimental animals.

Information office, increase of $31,000.—This increase would provide additional personnel to more adequately translate scientific programs and developments of the National Institute of Dental Research into information understandable and usable by the general public and interested lay organizations and groups. It would also permit the information office to more effectively assist the scientific staff in their communication with the rest of the scientific community through facilitating the editing, publication, and distributon of research papers and reports.

Research services section—increase of $23,000. This increase would provide additional central research services required because of the expanded laboratory

programs.

Included in this request is $214,000 which represents an increase in the NIH management fund for centrally furnished services.

B. Collaborative studies, difference of 1 position and $415,000

This difference would provide additional funds to support one position and additional research through contracts in the following areas of investigation: (1) Characterization of tooth surface changes caused by different cutting procedures; (2) microstress measurements on the dentition, and the effect of such stress on the physiology of supporting tissues; (3) the development of a test erhanism for routine screening of teratogens which may cause birth defects of left lip and palate; and (4) epidemiological studies of the efficacy of topically applied fluoride gel in school populations.

C. Review and approval of grants, difference of 3 positions and $85,000

The difference would provide additional funds and three positions for the necessary scientific and clerical staff required for expansion of the several grant programs.

It would also provide $35,000 for centrally furnished services from the NIH

Management fund.

D. Program direction, difference of $30,000

This difference would provide additional funds to support the Office of the Director in the overall planning, direction, coordination, and evaluation of the Institute's programs.

It would also provide $23,000 for centrally furnished services from the NIH management fund.

The following information reflects this Institute's professional judgment of additional funds that could be effectively applied to its programs:

Research grants, increase of $7,365,000

Through congressional appropriations the NIAMD has been able during past years to support the growth of basic research in the multiple areas of clinical disease that are its responsibility. Strong research groups have been formed and many young and brilliant men and women have entered productive investigative careers. The result has been increasing numbers of research grant requests submitted for funding to NIAMD. In this Institute as a result of recent congressional mandates, research in renal disease, dermatology, diabetes, gastroenterology, and orthopedics has been stimulated and a satisfactory gain in these areas has been shown. The suggested increase would enable the Institute to continue to support research proposals of excellence from the increasing numbers of requests in all of its areas of concern.

Training grants, increase of $643,000

Training grants have had a great favorable impact on production of physicians capable of critical investigation in the areas of medicine which are the responsibility of this Institute. Initiation of these programs in three new areas has been undertaken during the past 2 years. These areas are urology and renal disease. orthopedics, and dermatology. The budget level indicated would enable the Institute to continue encouragement of growth of these new programs and to maintain excellence of training in the other clinical areas.

Fellowships, increase of $371,000

The NIAMD has been able to fill more adequately the need for fellowship support by the increase in funds which the Congress has appropriated during the past 2 years. The projected budget would enable the Institute to continue support of the increased numbers of applications on an adequate level. This increase would be of special importance in the developing fields of dermatology, orthopedics, renal disease, and urology. Identification and support of outstanding individuals for further training at this stage in the growth of these areas of medicine is particularly critical.

Collaborative studies, increase of three positions and $800,000

This increase would provide the resources which could be effectively utilized during the coming year toward carrying out the congressional mandate to develop, with all possible speed, a simpler, more economical and more effective artificial kidney in order to bring this treatment within the grasp of all who need it.