The studies previously described have identified many factors involved in the pathogenesis of abnormal conditions and have shown that there are similar factors which also govern the pharmacological activity of various agents. Out of this peculiar relationship between abnormal conditions and agents has evolved a therapeutic method which is fundamentally different from methods in common use.

In conventional therapeutic efforts against disease—in chemotherapy of cancer for example—methods as standardized as possible are sought. The goal is to find agents capable of influencing the cancer cells, if not in all tumors, then at least in tumors of the same origin. Within the limitations imposed by the general toxicity of the agent, the conduct of treatment is standardized as far as possible. The criterion of value of a treatment is its ability to overcome individual variations.

In our approach, in clear contradistinction, the effort is to influence the complex condition as it is present at different levels of the organization. It corresponds to treatment individualized as far as possible. Therapeutic efforts are guided in all their aspects—choice of agents, doses to be used— by existing manifestations with their multiple quantitative and qualitative variations. The fact that many of these variations occur during treatment, as a response of the organism induced by the medication itself, increases the individual character of treatment. No prediction can be made about the whole course of treatment to be used for an individual patient because the individual qualitative and quantitative changes which occur during the treatment cannot be foreseen.

In this approach to therapy, the patterns of manifestations constitute the criteria which determine the choice of the group of agents, the specific members of the group, and the dosages to be used. Throughout, clinical and analytical manifestations are the major factors that guide treatment. The clear systematization of the relationship between analytical findings and therapeutic indications is vital.

The fundamental offbalances, their patterns and deviations, thus guide the therapeutic approach. The nature of the fundamental offbalance, in general, indicates which of the two basic groups of agents is to be used; the patterns show which substances from these groups are desirable; while the quantitative changes in these patterns, especially under the influence of the agents, determine the doses to be administered. Any change in biological manifestations is followed by change in therapy. We call this biologically guided therapy.

Through the years, although this biologically guided treatment has remained fundamentally unchanged as an approach itself, applications have evolved. Efforts have been made to find increasingly precise criteria and more efficient agents.

Each of the basic physiopathological concepts has greatly helped to develop standards for the guidance of treatment. For instance, the concept of organized conditions has led to the concomitant use of several agents from the same group instead of just one. The idea for this was derived from the fact that the concomitant manifestations at different levels show relative independence; they must be influenced separately. The concept of physiopathological dualism has indicated the need to use, according to the off balance present, agents from one or the other of the two groups with antagonistic properties. The role of the lipids in dualism has underscored the importance of these substances as active agents able to induce fundamental changes. The dualism of other constituents has been the basis for their use. The mechanism of natural defense has shown the advantage of using two systems simulating, in part, the kind of dualistic response which occurs naturally. As more has been learned about these basic concepts, the therapeutic approach, while it has remained fundamentally the same, has evolved and become increasingly effective.

The value of biologically guided chemotherapy appears clear when we compare the effects obtained by using agents with and without the guidance furnished by this method. Several patients treated at another center of research with a well known agent, such as a nitrogen mustard gas derivative, have been studied. Analytical data showing the patterns present in these patients were obtained but were not used to influence the conduct of treatment. Favorable results were seen in a few of these cases—when, by happy accident, the treatment applied was suitable both to the original problem and to the changes occurring during treatment, as revealed by analyses. In the failures, there was no such fortunate coincidence. The fundamental offbalance present called for an agent other than what was used. Or changes occurring during treatment indicated that use of the agent should be discontinued, although this was not done.

We have employed the same agents in some patients but with treatment guided by individual manifestations. In some cases, the analyses indicated the need not only for more prolonged treatment, but even for the use of dosages higher than those usually accepted. In others, on the contrary, they indicated the need to reduce dosage or even to stop the treatment, although the doses were, according to the usual posology, too small. It is interesting to note that in some cases, the treatment has been stopped and restarted several times on the basis of analyses. The clinical results—immediate and long range—were definitely better than in patients given unguided therapy.

In analyzing the development of clinical applications of this form of biologically guided chemotherapy, progress can be seen to have resulted as knowledge has increased in three areas: criteria, agents used, and method of application.