F

OR centuries the study of syphilis was exclusively a problem of human pathology and of clinical medicine. The clinician bore the responsibility alike for devising and for carrying out methods of treatment. In this undertaking he was guided almost entirely by two criteria, namely, the health of the patient and the ability to transmit the disease. But, with the discovery of the causative agent of syphilis and the successful inoculation of laboratory animals, this situation was changed. An opportunity was afforded for the study of syphilis by the use of laboratory methods and for carrying out experimental investigations of a type that hitherto had been impossible of approach. Thus, the past twenty years have witnessed developments in our knowledge of syphilis and changes in methods of diagnosis, treatment, and evaluation of the results of treatment whose importance can hardly be estimated. This we owe to a happy combination of clinical and laboratory investigations which is nowhere better illustrated than in the development of current methods of treatment, and future progress in this field is espe

1 Read before the joint meeting of the American Congress on Internal Medicine and the St. Louis Medical Society, St. Louis, February 19, 1924.

ANNALS OF CLINICAL MEDICINE, VOL. III, NO. 1

cially dependent upon a mutual understanding and cooperation of these two groups of workers. It is a clear realization of this fact that has led us to discuss the treatment of syphilis from an experimental point of view.

It is not our intention to discuss current methods of treatment as such, but rather some of the problems of treatment as they present themselves to an experimental investigator. In the present state of our knowledge it would be fruitless to undertake a discussion of the relative merits of the various systems of treatment now in use since there are almost as many methods of treating syphilis as there are clinics devoted to the treatment of this disease. Each clinic has developed a method of treatment applicable to its own practice which differs in some respect from that used in another. Moreover, while the majority of syphilologists employ arsenic, mercury, and iodine in some form, some clinics use one preparation and some another, and it would be very difficult to assign any definite reason, other than clinical experience, for the preference of one group of drugs over another or for the selection of the particular combination of therapeutic agents that is actually employed.

The great divergence of opinion as

to the relative merits of different systems of treatment or as to the superiority of one drug or combination of drugs over another is difficult to reconcile with any clearly defined purpose underlying the use of these drugs or with a clear understanding of their action. As a matter of fact, in the selection and application of therapeutic agents, we are guided very largely by clinical experience. Laboratory investigations have been helpful in some respects, especially so in the case of the arsenicals, but even here the evidence submitted is contradictory and there has been a notable lack of agreement between clinical and laboratory findings. Furthermore, it cannot be said that any considerable progress has been made in the treatment of syphilis during the past few years. There have been numerous additions to the list of therapeutic agents but none of them offers any great advantage over the older preparations. The noteworthy improvements have partaken of the nature of improvements in technique or the working out of more satisfactory methods for employing the remedies that are available.

To say the least, this is not encouraging from the standpoint of future progress unless we are able to make use of the valuable lessons that have been taught by experience. It is for this reason that we have taken the opportunity to direct your attention to certain aspects of the treatment of syphilis as a problem for experimental investigation.

The explanation of the situation that confronts us at the present time is to be found in the ideas and methods of investigation that have held sway

during the last fifteen or twenty years. We may ask, therefore, whether on the one hand, the conception underlying such a system of treatment as is represented by the "therapeia magna sterilizans" of Ehrlich is altogether sound or practical and includes all that is necessary in the treatment of a disease such as syphilis, and on the other, whether the experimental methods that have been employed in the evaluation of therapeutic agents are well considered or sufficiently accurate and comprehensive to afford an acceptable basis for the estimation of the probable value of any given therapeutic measure. To our minds, these are the two vital points upon which future progress in the treatment of syphilis will depend; hence they are worthy of careful consideration.

The conception of a concentrated attack on the causative agent of the disease by the use of powerful parasiticidal agents is one of the foremost contributions to the treatment of syphilis, and it is not unlikely that in time some agent will be discovered that is much more effective than any of those now in use. Theoretically, therefore, no objection can be raised to a system of treatment that has this idea in view. Practically, however, the point has not been reached where such a treatment can be applied to all cases of syphilis with any assurance of success; hence, the treatment of syphilis remains, as in the past, a task that requires the greatest skill that the clinician can command. Experience has shown that it is not sufficient to regard syphilis merely as a spirochete infection to be attacked by the use of the most vigorous parasiticidal measures that the patient will endure.

The treatment of syphilis is something more than this. It is, in a sense, a combination of applied pathology and pharmacology in that the selection and use of any therapeutic measure must be determined by the fitness of such a measure to meet the needs of a given situation. To appreciate such needs one must know syphilis in all of its aspects, clinical, biological, and pathological, and one must possess an equally exact knowledge of the behavior of any therapeutic agent. Not only this, but there is also need for an intimate knowledge of human economy, for after all, we do not treat the spirochete nor even the disease, but we treat the patient, and the resources of the patient are destined to become more and more important in the treatment of this as well as many other diseases.

The first problem presented by the treatment of syphilis is, therefore, the selection and the application of measures designed to accomplish particular purposes. Among these we must consider the destruction of parasites, the healing of lesions, and the preservation or restoration of the health of the patient. For this purpose we have three groups of therapeutic agents or measures: first, a group of specific parasiticidal agents including chiefly preparations of arsenic or arsenic in combination with antimony or silver and preparations of bismuth and mercury; second, two substances, mercury and iodine, the nature of whose action is somewhat obscure; and finally, there are a number of non-specific substances or procedures some of which are of proven value while others are of doubtful

utility. Among these we may mention hydrotherapy, radiant energy, protein injections, the use of vaccines or induced infections, and various endocrine products. For the most part, these measures are designed to meet particular indications as they may arise or for the treatment of some particular type of disease. They are of clinical rather than laboratory ori

gin and are of interest at this time chiefly on account of the fact that they indicate a recognition on the part of the clinician of a need to do something more than administer parasiticidal agents and of an effort to accomplish something by treatment of the patient, and it may be said that efforts in this direction are not without clinical and experimental justification.

But, to return to the questions under consideration, which of all of these substances or procedures is best and how may we use them to best advantage, or why is one substance or combination of substances better than another? It should be possible to answer such questions by carefully conducted experiments on laboratory animals followed by clinical correction and verification, but it must be admitted that thus far neither of these methods has yielded results upon which there is any unanimity of opinion, nor is it likely that any agreement will be reached until we approach these problems with a better understanding of the information that is desired and of the means that are available for the prosecution of such investigations. This may appear to be disconcerting, but it should not be so for it merely indicates a need for more comprehensive information, first, in regard to syphilis itself, and second,