The regional medical programs is the focus for NIH interest and concern in improving the delivery of health services. The British medical journal, Lancet, aptly captured the significance of the regional medical programs in calling them "An American Catalyst." In this catalytic role, this regional approach to health relationships must cause such diverse elements as medical schools, health professional organizations, individual physicians, hospitals, voluntary organization, and business and community planners to react together in a way which will promote, at the community level, the same high quality of medical care now available at our university centers of medical excellence.

One key element in the effort to translate research findings into improved patient care has emerged from the evolving regional medical programs. The practicing physician is the core of our system of health care, and his continuing education and retraining in modern medical precepts is crucial to the higher quality patient care which the regional medical programs has as a goal for the Nation. The regional medical programs can also provide some of the special diagnostic and therapeutic resources needed at the community level as more physicians require these complex new procedures in day-to-day practice. A general increase in professional sophistication can reduce significantly the toll of death and disability from disease.

Your final question was:

What further steps might be taken by Government agencies to bring about more biomedical development without diminishing basic research and without disorienting institutions involved in basic research?

I believe that we in the Federal Government need only adhere to certain commonsense precepts:

(1) The first imperative is to be certain that the science base for a proposed development effort has been carefully assessed by those most competent to judge these matters, and has in fact been found adequate. Another prerequisite is to be certain that the problem to be attacked is a major one; for a lesser problem would not warrant the heavy allocation of resources that may be required. Some very promising areas are research on containment, on the automation of clinical laboratory procedures, on centrifugation techniques, on models of complex biological systems, and on the computerization of hospital systems of drug dispensing, patient monitoring, and recordkeeping.

(2) A second set of requirements has to do with funding for developmental programs. If major new programs of this type are to be mounted "without diminishing basic research and without disorienting institutions involved in basic research," the new program must be funded on the basis of its own merits, and not as a substitute for the essential base of continuing scientific activity out of which emerge the developmental opportunities. Furthermore, the costs involved in the successful mounting and conduct of development programs must be recognized as high. Costs must, therefore, be projected realistically at levels that assure the entrance of very competent professionals into the area of activity if the objectives are to be attained and these in a reasonable time.

That concludes my direct responses to committee questions.

I would like to add an observation or two-and perhaps an example-to illustrate how we at the NIH view some of the more general problems of development and application in the biosciences.

Too frequently what seems to be a biomedical problem ideally suited to solution through large-scale development efforts proveswith more careful study-to be something quite different. I would like to illustrate this point with a brief discussion of the major health problem of chronic renal insufficiency-sometimes described as “kidney failure."

Hemodialysis through the use of the artificial kidney is a lifesaving measure which can sustain a substantial portion of patients with complete and chronic kidney failure in nearly normal activity for long periods of time where otherwise they would die. There are, however. technological problems with the equipment now in use. There is danger of infection, hemorrhage, and clot formation for the patient. In addition, this represents a huge economic burden of about $10,000 per year per patient. It is estimated that as many as 5,000 patients each year reach a stage of renal insufficiency that makes them logical candidates for use of such a device. The cost attendant upon the broad use of such a device on a nationwide basis is thus substantial. The amount of professional and technical personnel that would be required is also very large. A partial solution would appear to be simplification, through the development of a do-it-yourself-type dialysis unit. This, together with suitable training of family, would do the job at something less than half the cost. Another approach is to develop multiplepatient dialysis equipment devices to improve the utilization of the expensive equipment now required with a consequent lowering of dollar cost per patient. Efforts of these kinds are now underway in a number of places.

It is because of these facts that we undertook a developmental program to simplify both the device and the circumstances of its use some years ago. The extent to which this can be accomplished is not yet clear, except that substantial simplification is feasible.

Meanwhile, dialysis is an essential research tool that can lead to a definition of the specific biological factors that precipitate disability and death in chronic renal insufficiency. Clarification of these factors will greatly modify the next generation of devices. This objective has been brought closer by the recent demonstration of the effectiveness of diets limited to the minimal amounts of essential amino acids as the total source of nitrogen. Hopefully, this will permit definitive study of the origin and nature of the toxic substances that result in uremia and the consequent development of more specific methods than general dialysis as a means for their renewal.

Working in other fields relating to a clarification of the role of tissue antigens in the immunological rejection of organ transplants will lead to more general use of renal transplants, thus lessening the need to resort to hemodialysis as a maintenance technique. This, though, will not be the final answer to the problem of chronic renal insufficiency, since the condition largely results from three major diseases, pyelonephritis, which is repetitive kidney infection, polycystic kidneys or glomerulonephritis, a chronic disease characterized by acute phases typically leading to complete loss of kidney function. The latter disease

tends to attack the fresh renal transplant, destroying the new organ even as it had destroyed the original organ.

So one is driven back to the need to define the cause of glomerulonephritis; to determine the factors concerned with its progression; and hopefully, with such information, to prevent or modify the course of the disease. Here too there is progress to report in the recent development of an animal model system, occurring in a strain of hybrid mice, which for the first time offers substantial opportunities for systematic study of the disease in the laboratory.

The artificial kidney thus illustrates several points: both the complex biological questions as well as the many practical considerations that bear upon the decision to undertake larger scale expensive development programs, also the biological setting required if the overall activity is to be successful.

In conclusion I should like to summarize by emphasizing these fundamental points which embody the essence of what I have just said.

(1) Knowledge of life processes and of phenomena underlying health and disease is still grossly inadequate.-In the absence of broad general theory, such as exists in the physical sciences, the development of diagnostic, therapeutic, and preventive capability will continue to be dependent upon empirical approaches, serendipity, and the intuitive brilliance of too limited a number of gifted individuals. Therefore, the hope of major advances lies in sustaining broad and free-ranging inquiry into all aspects of the phenomena of life, limited only by the criteria of excellence, intrinsic scientific importance, and the seriousness and competence of the investigator.

(2) Contrary to general impression, the whole scope of the medical and related sciences is pervaded by a purposeful concern for achieving mastery over the hazards to human life and health.Research in the biomedical sciences contains a high component of practical and problem-oriented activity, though the extent of this portion lacks clear visibility. Unfortunately, research with practical objectives is too often equated with organized national programs such as cancer chemotherapy, vaccine development, or drug trials. It must be emphasized that such ventures are the exception rather than the rule. In the present state of our knowledge, there are only limited opportunities for highly organized research of a national nature with specific short-range goals. Such ventures must be very carefully selected, for they will be expensive, and, if undertaken in the absence of an adequate scientific base, may be unproductive and hence wasteful of limited resources.

(3) Despite the limitations of the base of biomedical knowl edge, progress in our medical capability has been substantial.The benefits of this progress, however, are not universally available. This is evident in the differential between the quality of medicine offered in the Nation's great centers of scientific and academic medicine and in too large a proportion of services at the community level. The solution lies not in medical science but in medical economics and sociology. In this area, the private sector has heretofore been dominant. But the critical nature of these problems has generated growing public concern and public action. If we are to preserve the private character of medicine in

this country, the problems must be attacked with greater imagination, concern for the public interest, and willingness of diverse interests to cooperate than has characterized the private scene thus far. The regional medical program of the NIH provides a unique opportunity for such a reformation in medical service. Finally, Mr. Chairman, I would like to say that I have been very much impressed by the general nature of the questions to which your committee has directed our attention. These have probed what I would agree are many or most of the key issues in the Federal science policy dialog underway.

You will recognize, as I do, that where there is more heat than light in these science policy debates, the controversial points have to do with means or priorities much more than with objectives. I think we can all agree that support for the biomedical sciences becomes meaningful in only one context-the effort to push as rapidly as possible toward solution of specific disease problems, and to improve, through health means, the quality of the lives of everyone.

Thank you.

Senator HARRIS. Thank you, Dr. Shannon. We are grateful for and honored by the attention which you have given these hearings and the interest of this subcommittee.

I want to compliment you on an exceptionally responsive statement you've made here this morning.

You have reminded us once again that we are not just dealing with research and its application, but we are also dealing with the sociology and economics of existing knowledge and facilities.

I particularly am impressed by your stressing a regional concept in building additional medical schools. In your statement you refer to an article in Lancet, and I am proud that the University of Oklahoma Medical School, in my own State, was mentioned by that magazine as being one of those involved in this "American Catalyst." I think we have to stress increasingly the regional approach in combating the social and economic barriers that retard the improvement of health.

Dr. SHANNON. Yes, sir.

Senator HARRIS. You are familiar with that medical program at our university?

Dr. SHANNON. Senator Harris, I am, indeed. I think it reflects the conviction of the regional medical programs that the circumstances that exist in diverse portions of our Nation are such that it is impossible to find general remedies that are applicable to all of these diverse situations. It is only through the thoughtful planning of sophisticated local groups, having quite diverse origins in the local society that effective means can indeed be developed.

Here I would concur wholeheartedly with the former speaker in that such involvement in planning and development is essential for subsequent effective action. I think you are very fortunate to have in your own State such a forward-looking group associated with the Oklahoma City Medical Center as a key to bringing these diverse interests together and developing an effective program. We look forward to a very successful program.

Senator HARRIS. I wonder if you might comment further on what developmental research activities NIH is presently supporting, and

what you consider to be the most promising opportunities for expanding biomedical developments assuming that the problem of budgetary restraints were removed or relaxed.

Dr. SHANNON. Well, I would be very glad to do that, Senator Harris. I have organized my thoughts on this because this was a very logical question for you to ask. What I might do is to outline the answer and then perhaps submit for your consideration and for the record an extension of those remarks.

Senator HARRIS. Good.

Dr. SHANNON. I will take this shorter aprpoach because my friend, Mr. Gorman, is getting uneasy back there. But there are a series of areas of strictly developmental character that are now underway. I might say that in the aggregate in the tabular material that I will present to you, these add up to $105 million, which, in round figures would be more than 10 and less than 15 percent of the total NIH enterprise. These cover a wide range of activities in all the affected diseases. They deal with rubella vaccine, respiratory viral vaccines, and certain problems related to the biological base of emphysema, which we spoke of before.

Senator HARRIS. What did you say after "emphysema"?

Dr. SHANNON. Emphysema, that was spoken of at some length by the previous speaker.

Senator HARRIS. I see.

Dr. SHANNON. In arthritis and metabolic diseases the primary thrust is in the field of the artificial kidney, but importantly, and not noted here, is a program in association with AID and the Department of Agriculture under the auspices of a Japanese-American agreement. This was worked out between the President and Premier Sato in the field of malnutrition and the development of nutrition-rich cereal grains. I mention that because it indicates a cross-government operation for a very important problem.

I would point out that our own country in certain segments of its population is not adequately cared for nutritionally, and I think that as we become preoccupied with problems of poor nutrition in other areas of the world where this could be the dominant concern, the information we obtain there is directly referred back to our own domestic situation, which, fortunately, is more limited.

In the Cancer Institute, there are special virus leukemia programs, programs in chemical carcinogenesis which address themselves to a variety of solid tumors, and cancer chemotherapy, again in relation to a number of specific end results.

In the Heart Institute there are three major programs, one addressing itself to the problem of myocardial insufficiency and the capability of aiding this with mechanical assistance devices. There is also the national blood resource program and a whole host of things such as, an agent we have for the first time that chemically can dissolve clots in large vessels thus offering a medical approach to what heretofore has been a surgical approach to such things as pulmonary infarction. This has been reported on recently.

In the National Institutes of General Medical Sciences there are such areas of study as automation, laboratory instrumentation, bioengineering in general.