We have discussed the different symptoms and analytical changes with dualistic character encountered in pathological conditions. At various stages, all were considered as potential criteria for guided therapy. The value attributed to them as indications for treatment has changed as research has progressed. Some of the analytical tests have been found to reflect changes limited to a special level, while others of more general value have been found to furnish indications of broader offbalances themselves. The importance of some criteria was established only after many years. Others, once considered of major usefulness, have appeared to be less reliable as time went on. Body temperature, for example, in spite of the frank dualistic aspect often seen, has been considered for a long time to be influenced by too many factors to furnish any valuable information. With the development of our research, however, temperature has become an important criterion for administration of agents but limited toward manifestations at the level of the organism.

Urinary specific gravity and pH; excretion of chlorides, sodium, calcium and sulfhydryl; total blood and serum potassium; and the count of eosinophiles in circulating blood—all have been used individually with the hope that they would indicate the type of fundamental offbalance present, and consequently, which group of agents should be used. Recently, however, we have come to use these measurements rather as criteria of changes at different levels. Urinary surface tension has thus become important as an indication of the offbalance at the levels above the cells while potassium in blood indicates the offbalance at the level of the cells. Years of investigation have shown conclusively that proper criteria represent the principal condition for success in treatment by guided chemotherapy.

The Agents

The relative independence of the various levels involved in a condition like cancer, which originates below the level of the nuclei and progressively involves higher levels as it evolves until it terminates as a systemic condition, necessitates having several agents chosen specifically for their ability to work at these different levels.

Over the years, we have utilized many agents. The level at which they are most active, the nature of activity from the point of view of dualistic intervention, and integration of activity in the frame of the defense mechanism, represent the factors which determine the specific use of these agents. It must be emphasized that, in the study of pharmacodynamic activity, the value of information furnished by tests in laboratory animals is limited. Because changes in patterns in animals cannot be followed, we have been obliged to follow such changes in humans.

Method Of Application

The critical role played by each level of organization in a complex condition—and the independence of these levels—underscores the urgency of applying therapeutic agents capable of acting at specific levels where they are needed. Such applications have been made possible through special affinities of various agents for different levels. Their structure—and especially their content of specific elements which belong to specific levels— account for their tendency to act at specific levels. However, it has often been judged necessary to insure intervention of an agent at a given level by applying it directly at the level itself. The injection of an agent into a tumor or into a region of the body, through surgical chemotherapy, represents one type of procedure insuring level activity. Another procedure has been to inject an agent prepared in vitro so that it is bound to specific body constituents, such as cells or nuclei. In the latter procedure, the specific defense mechanism is seen to take place at the level of the body constituent and thus desired level activity is obtained.

In the development of this research, we faced another problem which is basic to all therapeutic attempts but especially important in cancer: evaluation of the results obtained.

Evaluation

Incontestably, favorable results have been obtained in cancer with many agents. However, because of the variety of manifestations, evaluation of the changes obtained has been the subject of much controversy. Each clinical worker in cancer has his own ideas about the importance of various changes obtained and often utilizes as criterion changes less accepted by other workers. A systematization of evaluating standards appeared necessary and it seems possible to do so under the concept of the disease as an organized complex condition.

In the minds of most workers in the field of cancer today, any therapeutic procedure aimed at the control of cancer must prove itself in tumors in animals. We have already mentioned the reason why control of human and animal tumors represent two different problems. Failure to recognize that the results obtained in animal cancer do not necessarily apply at all in human cancer has led to failure of the tremendous project of screening virtually all known substances for their effects upon grafted animal tumors.

The unguided treatment of cancer in animals, as carried on today, i.e., without any consideration of existing offbalances, seems to explain the limited importance placed upon many changes obtained in these experiments. But even if evaluation is confined solely to the influence exerted upon the cancerous cells in unguided treatment, the same agent can appear active or inactive, depending mainly on coincidental circumstances. Its influence may change from favorable to unfavorable during, and due to, the treatment. Because of this, it is quite probable that many useful agents are not being recognized in the simple screening method used today. Most of the agents which we have found incontestably valuable in guided therapy appeared to be entirely ineffective when used in unguided treatments on small animals. As long as not enough valuable criteria are available to permit guided therapy in experiments in animals, the results would have only a relative value: to furnish useful information about limited problems such as toxicity, special pharmacodynamic activity, etc.

Under the concept of cancer as a complex condition, all manifestations, not just those directly related to the anatomical presence of cancerous tumors, must be regarded as important.

The tendency of almost all cancer workers is to limit evaluation exclusively to changes observed in tumors. Without underestimating in any way the importance of these changes, we must emphasize the importance of other manifestations. For a subject in the systemic terminal phase, any change obtained in the tumor will have little immediate importance, whereas a beneficial change in systemic metabolic anomalies will be of great immediate value. Similarly, for a subject in the invasive or painful phase, any influence exerted upon the organic or systemic functions will be of less immediate importance than a beneficial influence upon pain or upon the cancerous lesion. With cancer recognized as a complex condition, the decision of many scientists, especially clinicians, to limit evaluation to changes only in the tumors would appear to be unilateral and unrealistic.

We tried to systematize evalution of results obtained in cancer treatment by considering all the manifestations present in the patient and by assigning to each its relative value. In addition to any decrease or disappearance of tumor masses, various analytical changes, improvement in general well being, gain in weight and control of pain represent accomplishments, the importance of which depends on the severity of these manifestations in the individual case.

With all these factors in mind, we have evaluated the various results obtained through biologically guided treatment over a period of many years, relating them to agents and criteria which were changed, of course, as research progressed.

The study of different complex conditions has emphasized the fact that many of the manifestations present are common to different diseases. Through the variety of pathological manifestations present in these conditions, we had the opportunity to study many problems specific for these conditions or of general interest. The therapeutic method consequently has been applied in many noncancerous conditions. Before presenting an analysis of the progress of this research in the field of cancer, it may be of interest to review results of the same therapeutic approach in other conditions, each with its specific problems.