The migration of chloride in the blood was first investigated by Hamburger (1) who showed that when blood is exposed to increased tensions of CO2 there is a shift of chlorine ions from the plasma into the corpuscles. This phenomenon is known as the Hamburger phenomenon or chloride shift.

Many methods have been devised as adjuncts to clinical observation in the diagnosis of pulmonary tuberculosis. Leaving aside the use of the Röntgen rays and the method of cyto-diagnosis which at one time had vogue in France, the procedures may be divided into two groups: (1) those which depend on the observation of the effects of various extracts of the tubercle bacillus upon the patient; and (2) those which depend on laboratory observations upon various materials (sputum, blood, fæces, etc.). Among those in the former group are the tuberculin test, the Von Pirquet, Moro's cutaneous and Calmette's ophthalmic reactions. Their uses are limited. It is the methods in the latter group that lend themselves more readily to general use.

The use of malaria as a therapeutic agent in epilepsy was suggested by the known beneficial effects of other specific infections in this disorder. The earliest observation was probably that of Plato, who found that lepers were free from convulsions. A “tendency to respite which is sometimes temporarily induced in the course of the confirmed disease” (by febrile infections) is noted by Aldren Turner (1). Hamilton (2) found that of 11 cases who contracted typhoid 9 showed distinct temporary improvement, and 1 of these was free from seizures for four years. Maisonneuve and Gerard (3) reported cases of epilepsy whose seizures ceased altogether during 2 attacks of intermittent fever.

The value of sunlight in the maintenance of health has been recognized from early ages, and history records sun-worship by many nations in the past as well as at the present time. In Europe records exist of the use of the light of the sun for medical and surgical purposes since before the Christian era, but it was only towards the end of the last century that its possibilities began to be studied and the value of the electric arc lamp as a substitute recognized. In 1893 Finsen demonstrated the value of sunlight and electric arc radiation in the treatment of lupus, and at the beginning of the present century Bernhard of Samaden treated wounds and tuberculous lesions with sunlight. In 1903 Rollier opened his first clinic at Leysin, where he obtained excellent results in the treatment of tuberculosis, especially of the surgical type, by insolation in the brilliant Alpine sunshine. In 1908 Gauvain introduced heliotherapy at Hayling Island and at Alton. Nagelschmidt used the air-cooled quartz mercury vapour lamp for general irradiation in the same year, and in 1913 Reyn commenced the use of the carbon arc for the same purpose. The value of ultra-violet rays in the cure of rickets was not recognized till demonstrated by Huldschinsky in 1918, though Palm (1), as early as 1890, urged that deficiency of sunshine was a cause of the condition.

At the outset it may be desirable to give a brief outline of the phenomena upon which this work is based.

A complete historical survey takes us back to very early times, to the days of Hippocrates and in more recent times to the humoral pathologists, when the formation of the “crust phiogistica” or “buffy coat” was practically the only blood symptom known. Until the old humoral theories were discarded, that is until the rise of the doctrines of cellular pathology, the problem loomed large, but after this period interest in it declined, until the whole matter was revived about ten years ago by R. Fahraeus, of Stockholm, who published a series of researches into what he termed the “suspension stability” of the blood. By this term is meant the power which the plasma has of holding the erythrocytes in suspension. When the stability is lowered, the corpuscles sink with increased rapidity. This author found that a lowered suspension stability occurred in a large number of morbid conditions, and also in one physiological condition, namely pregnancy. Since the publication of this work the phenomenon in question has been made the basis of a test which has found considerable application in certain departments of medicine, notably in gynæcology and tuberculosis.

Within the last year a series of papers has been issued (1, 2, 3) from this laboratory indicating that in the psychotic there exists a disturbed regulation of the respiratory mechanism for the control of acid-base equilibrium, which, in the cases examined, mainly depressed psychoses, manifested itself as an inexcitability of the respiratory centre, shown by a failure of response to CO2 stimulation. The work was done on uncertified borderline cases of insanity; it has since been confirmed by Marsh (4) on certified patients, and his results in 73 cases confirm the original findings and indicate plainly that dementia præcox and depressive psychoses fall into a group showing a variable inexcitability of the respiratory centre. The question naturally arises whether this condition is a cause or an effect of the mental state, and, from the point of view of cause, whether it is due to the drug-like action of some substance arising from faulty metabolism, or is an exhaustion effect. The question of intestinal toxæmia obviously needs investigation in this respect. This subject has been freely discussed in the literature and its significance becomes of greater importance in relation to psychoses owing to the work of Buscaino (5, 6) and Scheiner (7, 8) in Italy, and of Stewart (9) in this country. Buscaino describes a reaction of the urine with silver nitrate in certain psychotic cases, alcoholic insanities and dementia præcox, and from this assumes the existence of a toxic substance from liver derangement in these cases. He further describes lesions of the small intestine of mental patients which may result in undue permeability of its walls; it is not proposed to discuss this latter aspect of his work, but to deal with his silver nitrate reaction.

My view that mongolism is caused by fœtal hyperthyroidism ceasing at birth, is based on the theory that if the known actions of hyperthyroidism on the embryos of animals, as proved by feeding experiments and otherwise, were at work on the human fœtus, the characteristic features of the mongol would be produced. Fœtal hyperthyroidism could not fail to cause abnormal endocrine inter-reaction, and it has been said that in every mongol some endocrine disturbance can be demonstrated. The action hyperthyroidism has on frog embryos, including the cutting out of the later stages of normal development and growth, and the action thyroxin has in retarding cell division and embryonic development, would explain the general arrest of growth and development of the mongol, including that of the skull and the brain. The same actions would also account for the coincident congenital anomalies, e.g., congenital heart lesions, cleft palate, hypospadias, undescended and undeveloped testicles, primitive hands and feet, syndactyly of fingers and toes, atresia of anus, spina bifida, etc.; these are also manifestations of arrested development, and in favour of a common cause for the local and the general defects, are the facts that both are symmetrical, and that there is a parallelism between the amount of general physical defect, the number of anomalies, and the degree of amentia.

Inasmuch as the following is a summary of results of investigations into the pathology of mental disorders that have been conducted at the Central Pathological Laboratory at the Maudsley Hospital during the past few years, I shall deal with the general results obtained by my co-workers in the broadest fashion, alluding only to such facts as appear to be relevant to the hypothesis I am putting before you. When the present investigations were begun we had already abundant evidence of anatomical lesions occurring in schizophrenia, worked out in this laboratory by Sir Frederick Mott (1), (2), (3), assisted by Mr. Geary. The completeness of this evidence is a matter of history and is not now seriously disputed. (A few of the slides from the collection left to the laboratory by Mott were here shown.)

[The following is an almost verbatim transcription of some impromptu remarks made before an informal discussion at a meeting of a local group of the Psychopathology Sub-Committee. These remarks are, therefore, very sketchy and unoriginal, and the reason for committing them to paper at all in such an unvarnished form, is briefly this:

Few medical officers in mental hospitals wish to master all the intricacies of psycho-analysis, but many seek some concise, elementary knowledge concerning psycho-analysis as a body of theories (rather than psycho-analysis as a technique). It is for these that the following recapitulation is being published, largely in accordance with the suggestion of members present at the original group meeting, and in the hope of encouraging others, equally unversed in the finer details of the subject, to come forward and discuss these problems.]

The fact that seizures indistinguishable from those of “idiopathic” epilepsy occur in a considerable number of nervous and other physical disorders has compelled us to regard this discharge of psycho-physical energy as a symptom only, and the treatment should therefore vary from case to case in accordance with the particular pathological causation. The majority of cases that one has to treat in a mental hospital are of the idiopathic type, and the treatment is often unfortunately of a uniform empirical nature. Within recent years, however, there has been a tendency to develop some definite conception of the perverted physiology of the disease and to exhibit treatment accordingly.

Psycho-ANALYSTS and other psychiatrists agree, I take it, that there are multiple causes for every mental breakdown. The exciting cause may not always be discoverable, but would be sought, if wanted, in the period immediately preceding the onset. Contributory causes can occur throughout life, from birth to the date of onset. It is agreed, also, that in addition there must be a predisposition (though the strength of this as a causal factor varies, roughly, in inverse proportion to the others). It is in the localization of the predisposing (and specific) factors that authorities differ. The older psychiatrists confined it to the lifetime of the ancestors; psychoanalysts accept, in general, what they have been told about ancestral responsibility, but have focused attention, as regards predisposition for subsequent breakdown, on a later period, namely the first five or six post-conceptional years. This they regard as the developmental period of the psyche, and they consider that influences at this time modify the organization in process of formation in a way that cannot occur later, but is not entirely predetermined in the germ-plasm. The difference is not merely temporal but also qualitative, for while other causes are mainly general (with perhaps some exception as regards heredity), the infantile predispositions are specific. That is, they not only partly determine liability to a breakdown under stress, but play the chief part in determining the kind of breakdown to be expected should one occur, and also the basic layers on which various character formations are built, although the superstructures may be very varied.

In the domain of literature there is no author who has probed so deeply into the human soul as Dostoevsky. Possessed of great powers of introspection, and having experienced a most varied career, he was well fitted for the task of analysing the human mind and its motives. His intimate contact with criminals of all kinds during his exile in Siberia, together with the fact that he himself suffered from epilepsy, made him especially qualified to describe subnormal, criminal and epileptic types. Such a type is portrayed in his masterpiece, The Brothers Karamazov, in the character of Smerdyakov; and as an example of amorality, this character is well worth study.

The recent contributions of Hunter (1) and Moynihan (2) are significant of the importance of focal infection or “sepsis” in mental disease. Cotton's (3) view that toxæmia resulting from focal infection is the specific cause of the “functional” psychoses is well known on both sides of the Atlantic. Further, his therapeutic claims for surgical detoxication are only too familiar.

In this hospital we have a routine differential diagnosis which is applied in all cases of suspected epilepsy and which is as follows:

1. (a) High blood-pressure.

2. (b) Trauma of vessels and angiospasm.

3. (c) Nephritis, subacute and chronic.

4. (d) Diabetes.

5. (e) Tabes dorsalis, tabo-paresis, neuro-syphilis and general paralysis.

6. (f) Hysteria.

7. (g) Epilepsy.

“It is at least conceivable that our present complacent assurance that every individual must live and act within the arbitrary limits assigned by conventional and purely artificial standards of conduct, or else be segregated from society, may be fallacious and inimical to the best development of the race.”

In an earlier article (vide p. 107) a preliminary report was made on the treatment of epilepsy by peptone, B. coli and papaverine sulphate; in the intervening months extended opportunity has arisen for comparing the various methods of treatment and endeavouring to form some opinion of their efficacy.

This discussion, which stood adjourned at the Quarterly Meeting held on November 23, 1928, was resumed at the Quarterly Meeting, February 14, 1929, under the Presidency of Prof. J. Shaw Bolton, D.Sc., M.D., F.R.C.P. (vide p. 1).

The scope of this work is to show the variations in blood-pressure and pulse, together with the secretory and vaso-motor changes, resulting from injections of adrenaline and pilocarpine. The response of certain reflexes is also recorded.

The points raised here have been brought up by the occurrence, side by side, of a number of cases showing the same peculiar factors in ætiology and course. The existence of such cases has been for long well recognized, but the clear-cut nature of the whole process has in those here mentioned been so marked that they have been selected to illustrate the operation of a mechanism shown in a lesser degree in very many of our hospital cases, and too often lost sight of.

The recent articles by Corper on a new method for the cultivation of the tubercle bacillus have stimulated interest in what has always been a difficult and tedious performance. Since cultural methods hitherto have not been much more delicate in the detection of tuberculosis than the microscopic examination of smear preparations of sputum and tissues, the latter has remained the popular choice, especially in ordinary hospitals. The guinea-pig inoculation method is unhandy and too expensive, and in any case detection of the bacilli in the inoculated animal has to be done by a microscopic smear preparation. The examination of smears of sputum and tissues seldom gives positive results in those cases where doubt exists. A negative result from a microscopic examination of a smear cannot be relied upon.