The subject of this thesis is the outcome of what might be termed a hereditary interest in the complex problem of the relationship of chronic infections to the psychoses and allied mental disorders. Circumstances enabled me, while still a student, to undertake very humbly the continuation of my father's researches in the Scottish Asylums' Laboratory at a point where his illness and death might have proved the closing of a long and arduous chapter. That this would have been so is, as far as I know, borne out by the fact that up to the present no work directly bearing on his later bacteriological studies has been published. The researches I have undertaken during the past six years have been an attempt to elucidate more clearly what exactly are the bacteriological factors at work, and, further, in what manner they attack the economy generally, and with what result. In my endeavour to verify and extend Ford-Robertson's views I have been singularly fortunate.

In recent years research into mental disorders has tended to become more and more the study of the pathology of the living. The advance of biochemistry has contributed in great measure to this practice. Although bacteriological research has, in recent years, been more extensively undertaken in connection with focal infection, it has, in the opinion of most, yielded disappointing results. The study of focal infection by bacteriological methods alone will not, I am afraid, lead us very far. Endeavour should be made to correlate its local and remote effects in disordered hæmopoiesis, disordered metabolism and disordered endocrines in relation to the internal economy of the patient. In mental disease especially this implies a knowledge of the individual's potentialities that have been predestined by heredity, and later moulded by environment—factors which largely determine the psychopathic tendencies of every one of us. The bacteriological researches of Ford-Robertson and McRae (1) strongly suggest that in mental disorders we are confronted by bacteria of a special type, which as chronic infective agents can probably only adapt themselves to a certain group of the general community having a neurotoxic susceptibility. If, then, we are to make further progress in this direction, we must search for and apply new methods of bacteriological technique, study our results, and attempt to correlate cause and effect. In this relation I shall refer to special methods which are an elaboration of my father's work, the value of which time and experience may prove. In spite of the great importance of the biochemical researches of recent years, I think it will be agreed that some of us, especially those who are clinicians, feel disappointed that so far they have not given us as much indication for scientifically applied treatment as we had hoped. May I suggest that the explanation for this is two-fold. Firstly, in forming the basis of any research the present tendency is to take mental disorders in groups, for example, dementia præcox, which has a wide range of symptoms and between which and other groups it is difficult to draw a line of demarcation. It seems to me that our knowledge of the somatic factors underlying mental disorder is as yet so limited that attempts to continue on these lines will lead us only hesitatingly along the path of progress. Are we not still at the stage where our efforts should be concentrated more on the individual as a problem in pathology which, when solved as far as our knowledge permits, can be correlated in the future with his or her psychogenic group? The second point is that in many instances our scientific work tends to run in too narrow channels; thus it must be frequently lacking in the invaluable support of parallel knowledge in other branches of laboratory and clinical experience. The most obvious example is the lack of adequate collaboration between the biochemist and bacteriologist. I know of no two sciences that can be welded together so opportunely. This combination can be taken a stage further: active and intelligent co-operation with the clinician and X-rays and therapeutic specialists should be sought to enable us to appreciate better the intricate problems we have to face. Some of you may, with reasonable grounds, accuse me of theorizing, and I should at this stage like to mention that before I attempted to put these considerations into practice in cases of mental disorder, I had had the opportunity of carrying out exactly similar lines of research on some hundreds of non-mental patients in hospital and private practice. The majority of them were cases obscure in ætiology and symptomatology. This scientific survey proved to me at least the value of comprehensive work on the individual, and how it enabled one to diagnose and treat many cases with some hope of success. During my two years at Wantage House (the new acute hospital attached to St. Andrew's), I have attempted to carry out what this experience has taught me, with the added advantage that the patients have been under my personal care. Further, there has been every facility for dental and general X-ray diagnosis, and, lastly, ample scope for treatment. The success of such a scheme is only possible by organization and the team spirit, and in this I have been singularly fortunate. The cases I am bringing to your notice are 4 out of some 120 which have been subjected to comprehensive overhaul. I will try to emphasize the salient features in each and correlate them with the mental disorder presented. In this way you can judge for yourselves if we have learnt anything that may in the future lead to a clearer conception of what may underlie at least some forms of mental disorder.

For many years psychiatrists have appreciated the clinical value of the Wassermann reaction, not only in diseases of the central nervous system, but in somatic infection in the psychotic and the mentally defective. As a diagnostic test for syphilis, reliance has been placed on this reaction out of proportion, perhaps, to its relative efficiency; sometimes without a full appreciation of the difficulties which the pathologist has to face in rendering the test as accurate as possible, and also of the fact that the results must be interpreted both on clinical and serological grounds. Adding to the difficulties of co-operation between the two groups of observers, there has been the fact that, owing to increased efficiency in anti-syphilitic treatment during the past twenty years, the strength of the reactions to be found serologically has become progressively less marked. Thus, it is inevitable that many of the methods employed hitherto, although at one time satisfactory and reliable, cannot now completely fulfil all the criteria of a reliable test so essential to accurate diagnosis and the control of modern methods of treatment. Further, and of even more importance from the point of view of research and of the necessity of making strict comparison of the results of one laboratory with another, it has been ascertained that very little uniformity of method exists. This lack of cohesion not only reflects upon the efficiency of the routine work and research in mental hospitals, but isolates them as a whole from the Ministry of Health venereal disease centres, in that in very many instances the methods employed could not be strictly compared. From these facts alone it will be seen that sooner or later the time was bound to come when all the requirements of a standard method should be investigated and, from among many excellent techniques, the difficult task be faced of choosing one or a combination of tests that would serve the needs of the clinician and serologist working in the domain of psychiatry. At the time of the inception of the Pathological, Bacteriological and Bio-Chemical Sub-Committee there was current amongst its members a desire that one of the aims of this section of the Research and Clinical Committee should be to investigate this difficult and highly technical problem of standardization. Thus, after the preliminary work of the Sub-Committee on various schemes of research had been initiated, I was asked at the meeting on February 13, 1929, to prepare a memorandum on a standard method of performing the Wassermann test. This report was entirely of a preliminary nature, and intended only to form a basis of discussion. While this was in course of preparation a questionnaire was sent to those mental hospitals undertaking serological work, with a view to ascertaining and contrasting in some detail the methods employed by each. In order that all interests in the various branches of psychiatry should be fully represented, it was unanimously decided that all members of the General Paralysis, Mental Deficiency, and Encephalitis Sub-Committees should be invited to co-operate. Thus, on May 3, 1929, a conjoint meeting was held at Horton Mental Hospital, Epsom, under the chairmanship of Dr. J. R. Lord. In the memorandum I dealt mainly with the work of the three laboratory conferences held under the auspices of the League of Nations in November, 1922, November, 1923, and May, 1928, the latter, held at Copenhagen, being by far the most important in its results and influence upon the researches into the serology of syphilis.

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