The activities of NIGMS constitute a program of fundamental research which have general relevance to, are supportive of, and essential to many categorical decisions. These activities have been centered in this Institute to provide a central focus for many areas of science that can best be supported and maintained within a central organizational structure. This Institute in addition has program responsibility in specially designated areas that do not logically fit into the major categorical structure of the remainder of NIH.

The categorical structure of each of the Institutes, in general, reflect their concern with a number of major disease entities such as heart disease, cancer, etc., or areas of scientific activity such as aging or child development. The programs contain a mixture of that which is fundamental to the disease under study and that which is applied and developmental. In such a structure that is an obvious need for program development oriented toward the development of a number of disciplines which underpin the activities of the several Institutes. For example, intrinsic in all categorical programs is a broad dependence on biochemistry, pharmacology, pathology, etc., and they will support research and training in each of these areas only insofar as these activities are essential for the purpose of the Institutes' specific mission-they will not in general conduct programs which will be in direct support of these disciplines as such.

The National Institute of General Medical Sciences has this responsibility and discharges it in a very specific manner. It has responsibility for the conduct of predoctoral training except so far as a minor portion is performed within a combined program project. It has the further responsibility to assay aggregate activity in both research and training and to provide for adequate balance and coverage. It must undertake specific program areas in general support and in programmed activity.

Although the National Institute of General Medical Sciences supports a broad program in most of the basic biomedical areas leading to the study of health and disease in man, it is difficult to delineate ites precise nature other than to say that the program seeks to improve clinical care and enhance basic knowledge. However, certain specific objectives can be identified with general goals and with the advancement of public health. For example, a program designed to automate clinical laboratories to provide faster, cheaper, more accurate, and more frequent analysis to aid in the diagnosis of disease would be of distinct value in the practice of medicine. The development of such a system is possible under the present state of technology, but would require relatively large sums of money to design process control and computer operation of clinical laboratories and to construct a demonstration unit. The money invested in such a program, however, would be repaid many times over in the reduction in the cost of hospital care. Trauma is another research area offering great potential benefit to the American people. Twenty-two million bed days a year at a total cost of about $16 billion are now invested in the care of accident victims. A small reduction of even five percent in the length of hospital stay, in the cost of treatment, or in the rehabilitation of the accident patient could result in savings of hundreds of millions of dollars yearly. Again, much of the basic knowledge and technical skill are available to develop such a program. Research in this area, however, requires expensive clinical facilities and highly skilled teams of medical scientists.

Distinct improvements are also possible in the area of the clinical sciences. Every patient undergoing surgery requires anesthesiology and usually some form of diagnostic radiology. Improvements in techniques of patient monitoring.

radiology, and automated anesthesia could result in tremendous savings in the general area of patient care. In these clinical specialities, a basic-science base in biomedical engineering and control theory must be constructed before the technical innovations can be produced. As a result, goals in this area are not as sharp as those mentioned above.

A more indefinite though obtainable goal, and one of incalculable benefit to medical care, concerns application of knowledge of the structure and function of drugs to new methods of treatment in the area known as clinical pharmacology. In this field a basic structure of knowledge must be built on the metabolism of drugs with new therapeutic effects and the study of the relationship of one drug to another when they are administered concurrently. Once this basic information has been obtained, it will be possible to design drugs with greater therapeutic efficacy and lower toxicity.

Of great importance even though the knowledge they yield is not of an applied nature are programs in chemical genetics, which may provide better understanding of urban population problems, new social structures, and man's capacity for adaptation; and finally, the general support of basic science which is indispensable to the growth and development of applied research, from which eventually come practical advances in health.

The net increase of $7,943,000 for regular research grants will be used as follows: $6,928,000 for noncompeting continuations for increased costs and support of 168 additional noncompeting continuations, $697,000 for competing projects and $318,000 for supplemental awards.

The net increase of $2,148,000 for special programs includes increases of $1,792,000 for general research support grants and $500,000 for anesthesiology and diagnostic radiology centers offset by a decrease of $144,000 for scientific evaluation and planning functions transferred to the National Institute of Mental Health as part of the Public Health Service reorganization.

Program plans in 1967 and 1968

The next year will see continued support in those areas of science which offer promise for the future (genetics, molecular biology, energetics) but with a shift in support towards the physical sciences and their application to biological problems. Along with the stress to be placed on physical methods there must, of necessity, come an emphasis in practical application to bring the fruits of technology and quantitative biology to the physician and the bedside.

A program for the broad support of the basic medical sciences which may be applied to problems of human health must of necessity be very diverse. It is determined in part by the interest of the scientific community in problems of current emphasis as determined by the receipt of applications from that community. The mass of applications coming to this Institute in the form of so-called "undifferentiated” or “unstructured" applications may actually be grouped into definite programs indicating trends of science. On this basis this Institute will support programs which may eventually result in information on how cells react in disease states, bioenergetics which may be related to problems of health and basic nutrition and to the way which energy is transferred in the individual cell. Problems of human adaptability and the way in which the human organism responds to diverse environment which may some day permit man to live on the bottom of the sea or at high altitude are under exploration.

The large multidisciplinary areas of so-called unstructured research comprises about 80 percent of the budget of this Institute. Important and significant findings may be startling and unpredictable not only within the program of the National Institute of General Medical Sciences as a special case, but within any large collection of research projects where the fundamental knowledge is applied to a specific clinical problem.

Studies of the mechanisms underlying life processes through the application of the principles, concepts, and tools of biophysics, biomathematics and bioengineering are the mainstay of the biophysical sciences program. Support is provided for studies devoted to the development and application of instruments and techniques including X-ray crystallography, mass spectrometry, electrochemistry: the determination of molecular structure; and construction of special purpose equipment necessary in the investigation of the quantitative aspects of the biomedical sciences, including development of automated clinical laboratories and research on patient monitoring. Support is also provided for research projects devoted to systems analysis, feedback controls, operations research, bionics, com

puter technology, ultrasound in diagnosis, and clinical monitoring devices and systems.

Particular stress will be placed on projects devoted to clinical applications of biomedical engineering concepts, such as clinical use of ultrasound visualization systems and their diagnostic application. Research on biomaterials concerned with the theoretical and practical application of metals and plastics in repairing or replacing tissues affected by trauma or disease will be encouraged.

Clinical research concerned with human and animal study, employing basic biochemical and biophysical principles and concepts, is the primary mission of the medical sciences program. Special emphasis will be placed upon investigation of mechanisms and treatment of burns, shock, wound-healing, tissue repair, and trauma in 1968.

PHARMACOLOGY-TOXICOLOGY PROGRAM

A program of pharmacology-toxicology centers was initiated in 1966 at a level of $1,000,000. These centers are university-based resources for both research and training and are thoroughly involved in graduate education. They are oriented to problems arising from the use of drugs and are designed to provide ready access to clinical material and to provide specialized laboratory and animal facilities. Careful consideration is given to the geographical location of these centers, as they must be able to compete for top-level scientific personnel in order to provide the scientific leadership necessary. Hence, locating them in appropriate academic, scientific, and cultural environments is given primary consideration, and has been found to be conducive to attracting the high caliber of manpower necessary.

Program plans in 1967 and 1968

Approximately 8 centers or large program projects will be supported in 1968. This includes a center now being fully developed at the University of Iowa, an active center at the University of North Carolina in Chapel Hill, and a center in clinical pharmacology at Emory University.

Under the Iowa grant, a vigorous research and training program in toxicology and biochemical pharmacology is under way. Long-range plans have been made to accommodate the center in major construction being projected for the medical school complex at Iowa City.

The project at Emory University proposes to investigate human drug metabolism and toxicology.

ANESTHESIOLOGY AND DIAGNOSTIC RADIOLOGY CENTERS

Few surgical procedures can be performed today without the use of a general anesthetic. Hundreds of thousands of patients are exposed each year to a variety of anesthetic drugs. There is a need for greater understanding of anesthetic compounds of new drugs to alleviate pain or to cause muscle relaxation and new methods for the handling of the anesthetized patient through patient monitoring devices and intensive care units. A center to explore this wide area of clinical medicine is necessary and NIGMS proposes to establish at least one such center during the coming year.

Radiology is an absolutely essential factor in assessing the damage, determining appropriate treatment, plotting the course of recovery, and evaluating the success achieved in many disease entities, including in particular coronary artery disease. The radiologist today must extend his services to more people in a given period of time which requires the development of computer techniques for storage and retrieval of X-ray film, new television techniques which will permit him to examine several patients from a central room and the development of new types of X-ray tubes and methods for the intensification of images. Such research leading to direct clinical application can best be done in a center where engineers, radiologists, basic medical scientists and physicians can be brought together in a cooperative venture to improve radiological science.

The development of a center for examination development and evaluation of new techniques in diagnostic radiology is planned in 1968 to bring the fruits of biomedical engineering to improvement of X-ray investigation and to develop new methods of visualization of tissues.

The aims of the Research Fellowships Program of the National Institute of General Medical Sciences are two in number. One is to increase the supply of manpower for the research needs of the country by the support of young capable investigators reviewed on an individual basis, and, secondly, to supply Special Fellowships Awards, Postdoctoral Fellowships and Career Development Awards to those more senior individuals who have already demonstrated a marked capacity for biomedical research in order to develop new skills, greater competency in clinical or basic science areas, or to permit training in multidisciplinary approaches to the biomedical sciences. This program is administered in a manner to supplement or extend the training provided through training grants. Program plans in 1967 and 1968

Predoctoral Fellowships are awarded to graduate students who are seeking a research degree in the biomedical sciences or in the sciences which may be closely related to better clinical care such as biomedical engineering or biomathematics. Support is now provided to predoctoral research fellows in more than 120 institutions. It is anticipated during the coming year that the number of institutions in which predoctoral fellowships are awarded will gradually increase as this Institute attempts to attain, without lowering standards, a wider geographical distribution of fellowships. At the same time the number of fellowships awarded in departments which also have training grants will be decreased. It is our belief that the support of graduate students is better obtained

through the milieu of a training grant than through the support of the individual predoctoral student for those demonstrably able and productive departments that have a firm record of successful training over the years.

Postdoctoral Fellowships provide support for one, two or three years of training to individuals who have already achieved a research degree. Such programs are structured heavily towards those areas of the biomedical sciences in which new advances are being made such as clinical pharmacology and toxicology, biomedical engineering and mathematics. The development of a program in clinical pharmacology utilizing the best skills of the basic pharmacologist, together with the talents of the clinician, can be best mounted by postdoctoral training of Ph. D.'s and M.D.'s in this area. Such postdoctoral training can be achieved by the postdoctoral fellowship and by special fellowships awarded to highly competent individuals who wish to continue or increase their training in a particular area.

Special Fellowship support will be provided to carefully selected individuals interested in obtaining advanced or highly specialized training for research. Special program emphasis will be placed in such areas as pharmacology and toxicology, biomedical engineering, selected areas of anesthesiology, diagnostic radiology and surgery.

The Career Development Award Program provides stable support for up to five years or more for individuals who have demonstrated a capacity for research in a productive scientifie environment and who have not yet obtained recognition as established investigators. In 1968 it is planned to continue program emphasis in those areas mentioned above such as pharmacology and toxicology, and biomedical engineering. Postdoctoral, Special and Career Development Awards will also be awarded in the fields of anesthesiology, radiology and surgery in an attempt to develop these fields to their fullest research potential.

Because of the decreasing predoctoral program and the rapidly increasing postdoctoral research support program proposed, the 1968 estimates will support 150 less predoctoral fellowships than in 1967, but will permit a continuation of the shift of program from predoctoral to postdoctoral emphasis. The special fellowship and the career development award category will be expanded as will certain areas of postdoctoral fellowships (biomedical engineering), while certain other areas in this latter category (organic chemistry, biology, etc.) will be decreased, resulting in slightly fewer postdoctoral students in 1968.