THE new histological methods introduced by Altmann, Ehrlich, Arnold, and others, have enabled us to establish closer relations between the morphological appearances of the cell and its specific physiological activity. It is now undisputed that where a granular condition exists in the protoplasm of a cell we may assume that the granules are associated with some form of secretion, either internal or external, according to the anatomical relations of the cell to its surroundings. No wonder,

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... re, that histologists should endeavour to search for new methods to enable us to demonstrate internal secretion, under conditions where the ordinary methods of physiological research fail. Whac modern histology owes to Ehrlich, who first demonstrated the neuro-, lipo-, and polytropic properties of various aniline stains, needs no comment, since these investigations on the chemical affinity of certain aniline colours to animal tissues have resulted in chemotherapy and the discovery of salvarsan. The great gulf which separates anatomy, the study of the dead, and physiology, the study of the living cell, has now been bridged by the introduction of intra-vitam staining, which though in its infancy has already yielded results hitherto unapproached by other means. Through the liberality of Professor Ehrlich I became acquainted with various aniline colours which after injection produce a more or less rapid and universal colouring of the skin and various internal organs in mice, rats, guinea-pigs, and rabbits. The best results in intra-vitam staining of rats are achieved by subcutaneous injections of a 1 per cent. solution of isamine blue, 1 grm. per 20 grm. of the animal's weight. On the beginning of the third day a faint blue appears on the animal's ears, and then the blue colour gradually spreads over the whole surface of its body. Repeated injections at intervals of 8 to 10 days increase the intensity of the colouring without impairing the animal's health. But the stain is not restricted to the surface ; we find it microscopically throughout the whole of the body, always embodied in granules of specific cells. Thus in the skin the stain is found in the granules of the fixed connective tissue cells of the cutis, but chiefly in free round cells belonging to the lower layer of the subcutis. Here the cells aggregate in great numbers, and especially in spots where an irritation or lesion of the skin is produced by artificial means or by pathological processes. These cells, which belong to the type of the " histogenic migratory cell," are by no means confined to the skin ; they appear in every internal organ (with the one exception of the nervous system) and always in connexion with interstitial fibrous tissue. We find them in muscles and tendons, in glands, but especially in serous membranes-e.g., in the peritoneum-whose taches laiteuses seem to form a matrix for their production. By means of the intra-vitam isamine blue stain we can differentiate the "Kupffer" star cell in the liver, the reticulum cell of the lymph glands, the spleen and bone marrow, the interstitial cell of the testicle, the follicle cell in the maturing Graafian follicle, cortex cells of the suprarenal, the epithelial cells of the choroid plexus, and the epithelial lining of the convoluted tubes of the kidney. Most striking is the appearance of the placenta and its behaviour in relation to the rest of body. When pregnancy occurs in the vitally stained animal the blue colour disappears from its skin and is concentrated in the uterus, the latter forming a centre of attraction for the vital stain, and actually dispossessing the remaining tissues of their blue. In the uterus we find the blue chiefly in the free cells of the decidua serotina, but also in the cells of the reflexa during the period of its existence. In an early stage of pregnancy (sixth to eighth day) these granular cells in the decidna of peritoneal descent cast off vitally stained granules which are eagerly snatched up by the foetal components of the developing placenta. Once the placenta has attained its maturity, we discover the vital stain in the "giant cells" forming the boundary line between the maternal and fcetal part of the placenta. We also find it in those fcetal cells which constitute the only barrier between the maternal blood spaces and the endothelial-lined capillaries of the foetus. Finally, the vital stain effects a most striking specific differentiation in the granular cells of the vitelline membrane. Notwithstanding the fact that the yolk membrane is deeply stained throughout its whole extent and that the amniotic fluid shows a faint bluish colour, the embryo remains perfectly colourless, the placenta and its appendages thus forming a protective barrier against the passage of the stain from the maternal into the fcetal organs. Although the stain circulates in the blood no blood cell accepts it, nor has it any effect on the cells of the vascular coats. After many futile experiments I finally found ways and means of fixing the vital stains, so that we can now prepare permanent histological specimens which recall the conditions of the living cells in all detail and accuracy. As a rule, we inject the acsesthetised and deeply blue-stained animal from the beating heart with formalin solution, open the body cavities by a median incision, and immerse the mouse or rat in formalin. In 48 hours the vital stain has become sufficiently fixed in the cell to allow of the preparation of sections. I have specimens which have not faded in the least within the last three years. As the vital strain is strictly confined to the protoplasm counter stains for the nucleus, &c., are necessary. Ovum and Placenta. My studies have been confined so far to the rat and moase, since these animals still form unrivalled material for cancer research. I will first take up the remarkable conditions revealed in the ovary and placenta. As the primordial egg cell grows into the Graafian follicle the inner layer of follicle cells display granules in their protoplasm which show a marked affinity for the blue of the vital stain, whereas the ovum itself shows no trace of blue. The question arose as to whether these follicular cells are the bearers of any special nutritive material which the ovum receives before it bursts the follicular membrane and starts on its downward journey. I first applied the ordinary fat stains, such as osmic acid, Sudan and scarlet red, only to corroborate a fact frequently mentioned by various authors, that the inner follicular layer of cells gradually succumbs to "fatty degeneration." Here, again, we discovered that although the cells immediately contiguous to the ovum were highly charged with fat no fat or lipoid substance could be found in the ovum itself. It seemed, therefore, the more remarkable that on application of glycogen tests the result in the maturing ovum was positive, whereas in all the remaining cells of the follicle and the ovary the test failed. On full development the protoplasm of the ovnm is rich in glycogen. In sections stained by Best's carmine method the ova show a brilliant red in their protoplasm and a rich red in their nucleolus. In order to avoid decomposition of the relatively small amount of glycogen found in the minute ova of mouse and rat, it is essential to precipitate the glycogen rapidly by means of alcohol injection from the beating heart of the anassthetised animal according to the method mentioned before. Without these precautions glycogen in the ova becomes invisible. Hence the fact that so many have failed to trace it in the ova by the ordinary methods. Oddly enough, I have found in the ovaries of rats and mice, and especially in such as had been tumour bearers, ova in various stages of division. In one specimen within the zona pellucida of the ovum no less than five cells with well defined nucleus and nucleolus were discovered. The ovum lay either in the centre of the follicle or in an eccentric position apparently dislocated thither by the abnormally widened follicular cavity. The membrana granulosa had disappeared almost completely. Such ova had all the appearances of a morula. The cells constituting the morula were richly filled with glycogen granules.