In the development of psychiatric genetics progress has been very largely dependent on the progress of clinical psychiatry. In the early days the theory of polymorphism held the field—that is the idea that there is a single hereditary basis for what may be called degeneration, which might show itself in many forms, any form of insanity, psychopathic character, criminality or mental defect. This theory was built up on the unclear psychiatry of the day, when the boundaries between different clinical states were vaguely drawn and largely in dispute. We are now passing out of this stage in clinical psychiatry, but the genetic theory that was built on it, the idea of polymorphism, still lingers on. It has been the stimulus to an immense amount of muddled research of no value. The time has come when this theory should be finally discarded. We are not entitled to think that different clinical conditions have the same genetic basis until such has been proved. From a factual point of view the accumulation of knowledge has shown it in a number of cases to be untenable. From a heuristic point of view it offers no possibilities of advance.

I want to speak of the work we have been doing in Cardiff on the metabolism of the nervous system. The work was carried out there because of the importance of the narcosis treatment. It seemed to us there a pity that a treatment such as that should be given up because of the considerable toxicity possible in relation to it. The research was undertaken to see if we could diminish the toxicity, at the same time seeking an idea as to how narcotics work. I ask that you will realize that the main substance burned by the brain is glucose. The dominant form of metabolism in the nervous system is connected with the breakdown of glucose and lactic acid, and this can be proved by experiment in the living animal and with brain-tissue in vitro. In doing experiments we are not able to carry out work with human brain, because we cannot get human tissue fresh enough, so we have to carry out experiments with animals. They are carried out in this way. We cut slices of the cortex of the brain as soon as the animal is dead, that is to say, within ten minutes of death the brain is out and slices have been cut. They are placed in a physiological medium in the presence of glucose, and we follow the metabolism of that tissue, which allows us to estimate the amount of oxygen being taken up by the brain. If luminal, chloretone, hyoscine or somnifaine be placed with the brain-tissue, then the respiration, instead of being at the usual level, starts lower down, and maintains a straight line. We wanted to see whether this action is reversible or irreversible. If the latter, then on removing the brain-slices from the narcotic it should no longer behave like a normal piece of tissue. Actually, when the brain-slice is removed and placed in Ringer solution, with no narcotic, the respiration goes up and becomes equal to that shown by the slice which had no narcotic. That is to say, the process is reversible.

The material on which this communication is based was obtained during a survey of all the patients in Severalls Mental Hospital, one of the objects of which was to obtain information about the incidence of the various types of mentally disordered and mentally defective patients. An account of this survey was published in the Journal of Neurology and Psychopathology for January, 1936. For the purpose of the present more detailed analysis of the results relating to manic-depressive insanity and mental deficiency, mental ability has been graded as (1) feeble-mindedness, including all patients certifiably defective, (2) dullness, i.e., subnormal ability without certifiable defect, (3) normal.

The occurrence of irritability has been described in most text-books as a symptom in manic and depressive states. The causation of this symptom and the circumstances in which it is observed, have not received much close attention. Most authors put the states of irritability under the heading of mixed states. They cannot, however, be regarded as such in a strict sense, because the effect of irritability brings into the picture something new which cannot be derived from a mixture of the basal manic-depressive symptoms.