all its limitations the treatment is workable because of the continuing improvements which have been made by a number of investigators around the world. Overall results are reasonably good and, in fact, patients are beginning to travel now. They can arrange for dialysis in other cities, and in the jet age they can make quick trips between dialyses and return home in time for their next treatment. One of our patients is a consulting engineer who makes several trips a year to the east coast. So overall it is fair to say that in 1966 an emotionally stable mature adult has about a 90 percent chance of living a reasonable life for an average of 10 years on chronic dialysis. That statement represents a projection since the original patients have only gone 6-plus years, but we think on the basis of this experience that 10 years is a reasonable life expectancy. This prospect presents a serious and unprecedented problem that lies at the heart of my discussion because it exemplifies what can happen at the frontiers of medicine today.

THE PROBLEM

The fact that chronic hemodialysis has proven successful presents us with some staggering projections relative to the number of patients who could benefit from the treatment and who will die without it. Five thousand patients with endstage kidney disease who could be restored to productive living will die each year in the United States for lack of this treatment. The figure might be 2,000 or it might be 10,000; we really do not know at this point how many patients are involved. The treatment presently costs somewhat under $10,000 per patient per year. If we use the $10,000 figure and assume a life expectancy of 10 years and add 5,000 new patients each year, we will have 50,000 patients on dialysis at the end of 10 years with an annual national budget of $500 million coming from somewhere: from the patient, the community, the Federal Government. Therein lies our problem. Now, where do we go from here; what do we do?

THE DILEMMA

Let us look at the issues that are involved in trying to bring this lifesaving treatment to the patient with chronic uremia. As with so many areas of medicine these days, there are many vitally important activities in the kidney field that are in urgent need of support. These include:

1. Research into the cause of kidney disease.

2. Research on renal homotransplantation.

3. Lifesaving treatment by means of homotransplantation.

4. Research to improve chronic dialysis.

5. Lifesaving treatment by means of chronic dialysis.

The dilemma is whether or not we can afford the funds, facilities, and manpower to undertake No. 5. Are we going to commit ourselves to an annual budget of $500 million and perhaps shortchange points 1 to 4? Obviously not. It would be foolhardy to start at the bottom and work backward. We must start at the top and work down. Artificial dialysis is just an interlude-a step on the way to the total conquest of kidney diseases in particular and many diseases in the more

general sense. Our first concern should be with the quality and the quantity of the basic research effort that has brought us this far and, if there is hope in the future, must carry us on to even greater achievements. Hence, basic research dealing with the causes of kidney disease must have top priority. When I am talking about the cause of kidney disease, I am talking about the whole problem of studying how the kidney works and therefore how other organs work and how life itself works in terms of the biochemistry, the cellular physiology, the general physiology and the normal function. You must understand the normal function before you can understand the disease and its causes. In other words, there is no question that we have to put our major hope and faith in the cure of disease because the immense effort and expense of large-scale treatment of endstage kidney disease would be unnecessary if we could prevent or cure the kidney disease itself. Dr. Amos has very ably discussed the issues with respect to research on transplantation which obviously must go ahead full speed because of its enormous potential, not just in the area of kidney transplantation but for the replacement of many other vital organs.

As to the question of treatment by means of a transplant, most people working in the field feel that we are not yet ready to launch upon a full-scale treatment program and try to offer a transplant to the many thousands of patients who need this treatment. Whether we are ready or not, treatment by means of transplantation is going to pose the same dilemma that chronic dialysis is posing right at the moment. Hence, any decisions made relative to the enormous problem of providing treatment to thousands of patients by means of chronic dialysis well may have an important bearing on how best to organize large-scale treatment by means of transplantation should that step be undertaken.

These two methods of treating endstage kidney disease are intimately interrelated in many other ways, so let us examine briefly some of these interrelationships.

There are many unsolved problems relative to the use of dialysis to treat human beings with permanently destroyed kidneys. A particularly challenging one is the problem of treating the child who must grow and mature. As Dr. Schreiner mentioned, what seems to be at first a very practical advance in terms of saving human lives wtih a shunt and an artificial kidney brings with it a whole host of new problems, and this problem of growth failure is one of them.

The young lady pictured in figure 11 has been on chronic dialysis for 5 years. She is very smart. She just graduated from high school, but she does not grow. She is of very small stature and she has not gone through a normal puberty. In other words, the dialysis is good enough to rehabilitate her, but it is not good enough in its present form to permit growth. We are making some progress with a second child with more intense dialysis, but the problem remains that children cannot grow normally on dialysis. This problem introduces the idea that renal transplantation is going to play a very important part in solving problems for the patient who develops trouble with dialysis. This child in figure 11 (and she is no longer a child, she is 18 years old) is going to receive a transplant in the near future in the hope that while being maintained on a transplant, she will then have a growth spurt,

FIGURE 11. This young lady, now aged 18, has been on chronic dialysis for 5 years. She is a bright student, who has just completed high school. Failure to grow normally while on chronic dialysis represents a serious problem for such patients, who probably should receive a transplant.

go through puberty and become a normal adult female. There is encouragement here in that two similar patients have been transplanted at the prepubertal stage and have grown and matured sexually following transplantation. Whether we have waited too long with this girl at the age of 18 remains to be seen.

There are, of course, many other medical problems with chronic dialysis patients yet to be solved. For example, some patients on dialysis develop very weak bones. Perhaps by giving such patients a transplant they can refurbish their bones and be restored to normal, and if the transplant fails, then again dialysis. Most importantly, a renal transplant may represent the major hope for patients who for psychological reasons cannot cope with the emotional stress that is imposed by chronic dialysis. In fact, every patient on dialysis has the hope that some day he too can have a transplant and be free of the machine, free of the shunt, and as Dr. Amos said, restored to a fully normal life, and this hope makes it possible to live more happily with chronic dialysis.

There has been a lot of talk that transplant and dialysis are somehow in competition and one of the points we must get quite clear here today is that the two treatments complement each other completely, and if anybody has a chance for a transplant, a successful one, there is no question that it should be carried out. The rub comes, as Dr. Amos has very clearly indicated, in the maintenance of a successful transplant. A successful transplant must function on its own. In other words, the drugs used to control the rejection must be lowered to such a point that the patient is not made ill by the drugs themselves and if the rejection occurs, the patient's life must not be endangered; he must be put back on dialysis. These are goals that have yet to be achieved because both treatments are in such short supply, but they are attainable goals within the very near future.

On the other side of the coin, the logistics of operating a large-scale transplant program are, in fact, going to require that a large number of potential recipients; i.e, patients on chronic dialysis, be available for genetic matching to potential donors. If techniques for genetic matching that Dr. Amos and others are working on prove successful, and if one believes that in the future renal homografts should be obtained only from cadavers, then the only way to find a match for a given donor in the short time available before death is to have available a large pool of potential recipients, namely, patients on maintenance dialysis. What is likely to happen is that all patients on maintenance dialysis will be tested and typed by whatever means of genetic matching is devised. This information will be cataloged at the transplant center. Then when a potential donor is identified, matching will select those recipients with the best chance of compatibility. Of course, the larger the recipient pool, the better the chance for a match and the easier it will be to arrange for a recipient on short notice. Hence, a very careful overall plan will have to be evolved which limits transplant activity to regional centers with access to large numbers of genetically typed potential recipients.

Finally, there has been a worry, logically, that if we embark on a big and expensive program of dialysis, money will just be wasted and all of the facilities will be rendered useless and obsolete by the

future success of transplantation. Well, here we come back to the logistics of trying to treat 50,000 patients. Let us, in addition, predict that 75 percent of these 50,000 patients can be carried on a transplant for 10 years. This is, I think, a reasonable, although probably optimistic projection. Even so, we still are going to need to handle 12,000 patients at any one time on dialysis, which is about 20 times the number presently able to handle in the United States. Therefore, I think this question of obsolescence of chronic dialysis can be deferred at least until we can handle 12,000 patients. By tha: time we will have a much better idea of what percent of the total load can be handled by transplantation and then we can decide whether to go further with dialysis or whether transplantation can take the major burden.

So let us return to our dilemma and the question of whether we should support applied research at the practical end of the scale to improve the technique of dialysis. In the first place, I want to qualify the term "applied research" and at the same time underline what Dr. Schreiner has said; namely, that even though we undertake a missionorientated applied research program to improve the technique of chronic dialysis, a number of important fundamental problems invariably come to light in the process of carrying out this applied research, and the growth failure problem is but one example. Why doesn't our little girl grow? What is the biochemical basis of her inability to grow? This is a problem of enormous importance to investigators interested in growth and development.

As to the question of whether to support applied research on chronic dialysis technique, let us review some of the remarkable progress that has been made up to this point as a basis for predicting what may be possible through future research efforts.

The cannulas have been the weakest part in the dialysis system and they continue to be. But in 1962 Mr. Wayne Quinton, a medical engineer in Seattle, performed a really tremendous feat in learning how to introduce a little segment of silicone rubber into the cannula system as shown in figure 12. The reason this little rubber segment is so important is that a major cause of loss of cannulas has been related to movement of the hard teflon tip, irritating the vessel and causing it to clot. This little rubber segment acts as a shock absorber in the system and has greatly prolonged the life of the cannula. It represents a major step forward in cannula design.

A great deal of progress also has been made in learning to control some of the diseases that developed in many of the early patients on chronic dialysis. For example, neuropathy, a paralysis, was a devastating complication in the early days. This complication, we now know, is usually preventable by early and adequate dialysis. The same can be said for the arthritis which developed in some of the first patients. The problem of anemia is in the process of being solved. Whereas at one time we used as much as one transfusion a week to maintain the blood at a satisfactory level in these patients, now many patients do not need any transfusions. It is indeed true that research already has resulted in impressive advances in the management of the medical complications of dialysis.

In the area of techniques of dialysis the advances have been astounding. Figure 13 illustrates the way dialysis or the use of the