Mr. FLOOD. Thank you, Doctor.

Dr. Merrill?

Dr. MERRILL. Mr. Chairman, I too have a prepared statement which I believe has been distributed.

[The statement follows:]

Mr. Chairman and members of the committee, I am glad for the opportunity to appear before you today as a citizen's witness with special concern for the progress for the programs of the National Institute of Arthritis, Metabolism, and Digestive Diseases (NIAMDD). I am Dr. John P. Merrill, Jr., professor of medicine at Harvard Medical School. I have served as consultant to the Surgeon General of the U.S. Air Force, the Division of Urology of the National Academy of Sciences and the NIH. I am past president of the American Society of Clinical Investigation, the American Society for Artificial Internal Organs, and the International Society of Nephrology, and I have served as chairman of the Constitutional Committee of the International Transplantation Society.

I am a member of such scientific organizations as the Association of American Physicians, the American Federation for Clinical Research, the American Medical Association, and the American Clinical and Climatological Society.

My expeirence in the field of kidney diseases includes the development of the first clinically utilizable artificial kidney and the first successful kidney transplant, as well as the first home dialysis and peritoneal home dialysis.

I know that your committee has shown an abiding concern for the advancement of research programs against kidney and urinary tract disease. As you know, the kidney is the central organ in a complex physical system which normally carries out the task of removing end products of metabolism from the blood, thus maintaining a stable biochemical environment in the body. Approximately 42,000 Americans die every year from irreversible kidney failure which is the endstage result when kidney disease is chronic and progressive. As you know, treatment of end-stage kidney disease was the first catastrophic illness to be included in the disability medicare provisions passed in H.R. 1 in October 1972. Only through research can the clues be developed to mitigate some of the common kidney diseases before they reach the stage of terminal renal failure. Such endstage disease is usually not reached until the function of both kidneys has declined more than 90 to 95 percent. The period between the onset of kidney disease and the time when 90 percent of kidney function is lost is when we have the greatest opportunity to study how these diseases can be controlled and prevented. Without such research, kidney disease will continue to present us with staggering human and economic costs. Special diets may be useful therapy for a short time but ultimately renal dialysis with artificial kidneys or transplantation of a kidney will be necessary.

About three-quarters of deaths from kidney disease result from infectious, immunologic, and hypertensive types of kidney and urinary tract disease. If we are to reduce the number of these deaths, investigators must find better methods of earlier diagnosis, more effective therapy and ultimately preventive treatment, through greatly improved understanding of the causes and mechansims underlying these disorders.

For example, we know very little about the very serious group of kidney disorders which lead to end-stage disease, the glomerulonephritides. We know that we are confronting aberrant immune reactions, but we do not know what triggers them. We must find out what causes the inflammatory damage to the kidney in these diseases before we can hope to devise preventive measures. Advancements in this area are largely dependent on the progress that is made in the basic studies of immunology, just as is true in the area of rheumatoid arthritis research.

On the other hand, in the area of hypertensive kidney disease, we have seen great progress through the development of numerous antihypertensive drugs which are being used effectively to begin to manage patients identified in screening programs who, without such therapy, would eventually progress into endstage renal disease. We can expect to extend the benefits of this work of recent years to virtually hundreds of thousands of patients in the near future.

Most end-stage renal disease patients are now being kept alive with the aid of maintenance hemadialysis. This, of course, is now supported under provisions of the medicare law, hich has made it possible for these patients to receive the treatment they so desperately need.

70-075 76 pt.7 48

The quality of life on dialysis, however, is still far from ideal. The treatment itself is too lengthy and poses a burden for the potential rehabilitation of patients. Thus, any improvement in current dialysis therapy which can be developed by the Institute's artificial kidney-chronic uremia research and development program would enhance the medical rehabilitation of these patients and would make the currently lengthy treatment briefer and more effecive and economical. Such improvements will bring about significant human benefits in terms of well-being and ability to work full time, and will result in tremendous savings of Federal funds.

I understand that the work of NIAMDD's artificial kidney program has recently demonstrated that costly dialysis sessions ca be shortened considerably with the use of new types of dialyzers which have been developed. The value of peritoneal dialysis in treating certain patients has also been improved through recent research supported by this Program. This treatment can now be conducted at home at less than that of home hemodialysis. For many reasons, this treatment has become the most efficacious treatment for several classes of patients.

The artificial kidney-chronic uremia program of the Institute has now undertaken a longitudinal nationwide cooperative clinical trial to compare several dialysis therapies on a broad scale and to determine the feasibility of cutting the cost of the medicare program through a decrease in dialysis treatment time. This kind of comparison has never been performed before under the controlled conditions of these trials, and this work is extremely important if we are to have the kind of data in this field which will permit truly rational and adequate treatment of hundreds of thousands of patients, providing optimum care that is both effective and economical. Such a large-scale clinical trial costs millions of dollars, and organizing this one means that several million dollars worth of other essential uremia-related research cannot be undertaken.

NIAMDD has been the principal supporter of research in kidney transplantation. The kidney is the organ which is most frequently transplanted, the number now ranging in the tens of thousands, and we have recently achieved a reduction in mortality resulting from this procedure as compared with years past. Between 40 and 75 percent of kidney transplants now remain functional after 2 years. When the organ is derived from close blood relatives, of course, acceptance is more certain, and some recipients who received a kidney from their identical twin have now reached their second decade of life with the transplanted organ. Improvement must be made, however, in our ability to make use of cadaver organs in transplantation, and this is another area which depends so much upon our progress in research in basic immunology wherein the key lies to the acceptance of foreign tissue by the body.

This Institute is also working to effect improvements in artificial kidney equipment and methods of treatment, both to improve their effectiveness and to bring down the tremendous costs involved. These investigators and clinicians are also striving to improve the human conditions dependent upon improved methods of rehabilitation of patients on dialysis, and to decrease the incidence of long-term clinical complications associated with long periods of dialysis. The scientists are also working to find means of preventing the complications of longterm dialysis, such as bone disease-known as osteodystrophy—anemia, peripheral nerve damage, and premature cardiovascular death.

The Institute is employing the bulk of its kidney disease-related funds in support of basic and clinical research not related to end-stage kidney disease because it considers it a more desirable end to create the knowledge to control, cure, or prevent kidney and urinary tract diseases before dialysis and transplantation are required. Last year the NIAMDD sponsored a workshop on benign prostatic hyperplasia, a disorder related to chronic prostatitis, and which affects more than 60 percent of men over 60 years of age. The Institute is attempting to encourage new research approaches and directions in studying this disorder. It is felt that as better methods become available more specific research can be carried out in this and other closely related fields. More sophisticated approaches are being developed in hormone studies, in endocrinology, in virology, and microbiology, in biochemistry, with antibiotics, et cetera, and all of these should facilitate refinements in research into prostrate and other urinary tract problems. Advancement in all of these important areas is absolutely dependent on your support and appropriation of adequate funds for the efforts of this Institute to solve these multiple, grave health problems.

I can assure you that the research and development supported by the National Institute of Arthritis, Metabolism, and Digestive Diseases continues to be a vital major source of the knowledge and technology which is absolutely imperative to the task of combating kidney disease. I know that the administrators and scientists of this Institute are expending every effort to insure that the vigorous thrust of this program of research, treatment, prevention, rehabilitation, and education is effectively aimed at meeting the most urgent and significant challenges posed by these dire disorders. I am convinced that we must grant this work the highest level of priority in our health planning if we are to do justice in preventing disease and saving human lives.

I believe anyone familiar with the requirements in this field and with the limitations being imposed on progress by the ravages of inflation would insist that the administration's budget for this Institute fall far short of what is needed to carry out its mission. I encourage you to consider soberly the urgent need to increase these appropriations to avoid the consequences of neglecting some of the most important work there is to be done in biomedical research.

In summary, Mr. Chairman, this Institute has been responsible for the development and the promulgation of a workable program for saving thousands of lives each year which otherwise might die of end-stage renal disease. It has been responsible for technical developments which have grealty decreased the costs of this form of treatmnet and it has added greatly to our knowledge of the general problems of end-stage renal disease. While maintaining an interest in the progress of technical developments for life support in this area, the Institute is aware that techniques for the maintenance of life in end-stage disease are products of a "low technology" to use the words of Lewis Thomas, while "cure" of the disease by kidney transplantation, or even better, prevention by arresting renal disease before progression to renal failure is, again, in Thomas' words, a high order technology and success in these latter areas would result not only in better quality of life for patients but the savings of billions of dollars of taxpayers' money. The analogy to development of better respirators and the development of polio vaccine is, I think, an obvious one.

Finally, I would point out that the kidney is not simply an excretory organ but is concerned with the manufacture of blood, of hormones intimately concerned with bone metabolism, and that it is becoming increasingly apparent that the vast majority of patients with sustained and life-threatening hypertension have marked abnormalities in renal function and anatomy which may be responsible for this problem.

Work on the immunology of kidney transplantation has given us fascinating new insight into the orgin of many kinds of other diseases caused by antibody antigen complexes; among these, of course, are rheumatoid arthriits, various manifestations of systemic lupus, et cetera. Furthermore, investigation of the problems of kidney transplantation led to the delineation of human tissue types which we now know to be closely associated with a variety of diseases, including, of course, psoriasis and ankylosing spondylitis.

Moreover, it should be mentioned that transplantation biology began with tumor biology, the two have progressed closely through the years; a number of experiments dealing with graft rejection have also resulted in the production of spontaneous cancer, as have techniques for producing glomerulonephritis in animals. The incidence of cancer in patients who have had transplanted kidneys and immunosuppressive therapy in some 50 to 100 times higher than in age-sex matched individuals at risk. Thus the spinoff from this kind of endeavor may yield invaluable dividends.

I seriously commend to your consideration the citizens' budget which is submitted in the hope that our patients of today, as well as those who will be stricken in the future, may benefit from your compassionate planning in providing for this vital work. I would like to urge you strongly to support this budget, which, far from being extravagant, is based on realistic goals and which I believe, addresses what should be considered the minimal needs of this Institute. I am addressing myself not only to the dollars involved but also to an adequate increase in the manpower ceiling for this Institute, as described in the budget, without which it will not be able to carry out its many current activities and the new ones mandated by recent legislation.

Mr. Chairman and members of this committee, I would like to thank you for your continued interest and support of biomedical research, and for the privilege of testifying here before you.

FISCAL YEAR 1977 BUDGET PROPOSED BY CITIZENS FOR THE NATIONAL INSTITUTE OF ARTHRITIS, METABOLISM

1 Excludes provision for support of new programs, such as multipurpose centers, authorized under the "National Arthritis Act of 1974" and the "National Diabetes Mellitus Research and Education Act."

Dr. MERRILL. I would like to point out I am talking in the interest of kidney disease, and although kidney does not appear in the title of NLAMDD, tihs Institute has been instrumental in funding a considerable amount of research and making a considerable amount of progress against kidney disease.

I am Dr. John Merrill, professor of medicine in the Harvard Medical School and past president of the International Society of Nephrology. It was my group that conducted the first artificial kidney treatment in the United States and did the first successful kidney transplant in the world, so I have been interested in this problem for some time.

I believe you are aware of the fact that the Institute has had a fruitful program in the development of techniques and their utilization for keeping end-stage renal disease patients alive and in spite of the tremendous progress that has been made in machinery and apparatus thus is still what Lewis Thomas would call a low ordered technology. It is one in which we are treating the patient after the trouble has taken place. A high ordered technology would be one in which we have prevented the disease and the analogy of the artificial lung through to the development of polio vaccine I think is obvious.

At the present time, under medicare, the end-stage renal disease program in fiscal 1975 spent around $300 million in the care of patients with end-stage renal disease and the projection is that at this rate, by the early 1980's, it will be $1 billion.

I would like to suggest that the need for an increase in funding for this Institute is because we need research which will eliminate this disease, not simply to treat it after the patient has gone too far.

I would like to point out also. Mr. Chairman, that the kidney is more than an excretory organ. Artificial kidneys alone are not enough. The kidney, for example, is intimately concerned with the production

of blood, it is intimately concerned with the production of a hormone that regulates bone metabolism.

All of us have heard a great deal about the so-called silent killer, hypertension, and I think the evidence right now is very clear that the kidney is involved in most, if not all of sustained hypertension that is indeed killing people.

In addition to this, what we have learned from studying the immunology of kidney transplantation has been widespread, it has an intimate relationship with other diseases such as nephritis and rheumatoid arthritis and liver disease and others. Because one must type tissues in transplanting kidneys, we have learned humans do have different tissue types and we now know that some types are associated with different diseases.

For example, one tissue type is intimately associated with arthritis, one may even be intimately associated with diabetes. I think this kind of spinoff from research of kidney disease is extremely important.

Finally, interestingly enough, tumor biology and the biology of transplanted kidneys have gone hand in hand since the beginning, and their intimate association is, I think, extremely important. For instance, the incidence of cancer in patients who have had transplanted kidney is about 50 to 100 times higher than it is in the same age and sex matched population, and I think we have much to learn from this.

So, for these reasons and others, I seriously commend to your consideration the citizens' budget which is submitted in the hope that our patients today, as well as those in the future, may benefit from your planning and providing for this vital work.

In addition to the patients, of course, I would remind you of the financial savings should the spending for the end-stage renal program be eliminated by the elimination of the need to treat patients with end-stage renal disease through prevention before it got to that point. Thank you very much.

Mr. FLOOD. Thank you, Doctor.

Dr. Howard Polley and Dr. Donaldson.

Dr. DONALDSON. Mr. Chairman, it's a pleasure to appear before you on behalf of the consideration of the budget for the NIAMDD and I would confine my remarks particularly as it pertains to orthopaedic

surgery.

I am Dr. William F. Donaldson, the immediate past president of the American Academy of Orthopaedic Surgeons. I am a clinical professor of orthopaedic surgery in the School of Medicine, University of Pittsburgh, and I am a member of the National Commission on Arthritis.

I do have a prepared statement which I would like to submit for the record. And then, if I may, I would like to highlight certain portions.

Mr. FLOOD. Yes.

[The statement follows:]

With me is Dr. Edward Henderson, the current president of the American Academy of Orthopaedic Surgeons. He is professor and chairman of the Department of Orthopaedic Surgery, Mayo School of Medicine, and chairman of the Mayo Clinic's Department of Orthopaedic Surgery.

It is a pleasure to appear before you and the committee to present information relative to the appropriations for the National Institutes of Health (NIH) and,