blood vessels, and are swept onward until they reach the right ventricle of the heart, from which they are pumped into the pulmonary circulation. When they reach the small vessels surrounding the air vesicles they pass out of the blood vessels into the air cavities. From the time the larva perforates the skin until it arrives at the lungs it remains of the same size, but as soon as it reaches the air vesicles it begins to grow rapidly. It then makes its way out of the vesicles into the bronchioles, and, travelling up the bronchi and trachea, emerges through the larynx, and by crawling over the epiglottis passes into the oesophagus, and from thence into the duodenum. 5. Cytoryctes variola Guarnieri: the Organism of Small-pox. In spite of the fact that the organism of small-pox has come to be regarded by perhaps the majority of zoologists as an interesting but highly elusive species of will-o-the-wisp, I have had the temerity to bring before you still another attempt to describe and classify it. The present attempt goes back to 1892, when the Italian pathologist, Guarnieri, inoculated a rabbit's cornea with vaccine virus. Upon studying the tissues thus vaccinated he found in the epithelial cells peculiar homogeneous bodies of diverse form and size. He then examined skin from human subjects suffering the mild disorder, vaccinia, and skin from human subjects with the much more malignant disease, small-pox. In both cases he found bodies apparently identical with those previously observed in the rabbit. In the subsequent history of these diseases the peculiar structures came to be known as the 'Guarnieri bodies,' and were usually interpreted as degeneration products, although Guarnieri himself regarded them. as Protozoa, and called the organisms Cytoryctes vacciniae and C. variola respectively. The main reason why pathologists failed to accept Guarnieri's conclusion seems to be that his so-called organisms did not conform in any way with the postulates which Koch set up for the determination of bacterial disease germs. They had no apparent structure and could not be cultivated on artificial media. These objections, to my mind, were quite disposed of by the admirable experiments of Von Wasielewsky in 1901. He vaccinated a rabbit with a small quantity of virus; from this rabbit a second was vaccinated; from the second, a third, and so on until forty-seven rabbits were successfully inoculated without using the original virus a second time. In all the rabbits, after an appropriate period, the same bodies as those described by Guarnieri were found, and in approximately the same number as in the originally vaccinated rabbit. This result left only one conclusion, viz., that the questionable bodies had undergone growth and multiplication, the attributes of a living organism. Up to this time the Guarnieri bodies, or Cytoryctes, had been observed only in the cytoplasm. In 1902, Councilman of Harvard discovered peculiar and definite bodies in the nuclei of skin-cells infected with small-pox. He also found the usual cytoplasmic forms. This discovery led him, in April 1903, to publish, with Drs. Magrath and Brinckerhof, the hypothesis that Cytoryctes vaccinia and C. variole are one and the same organism; further, that the mild disorder, vaccinia, is characterised by the cytoplasmic phase alone, while the malignant disease, small-pox, is characterised by the vaccinia phase, plus the intranuclear phase. I was invited by Dr. Councilman to try to formulate a life history of the organism, and his splendid material from fifty-five different cases was generously turned over to my use. The results of this study were published this spring. To a zoologist confronted by the thousands of bizarre structures which fixed and stained small-pox material presents the problem seemed at first to be wellnigh hopeless. Added to the difficulties of interpretation from morphology alone was the fact that nowhere among the Protozoa are similar organisms known. The nearest analogies to the structures observed are in the groups Microsporidia and the bacteria, and it is because of these far-away resemblances that I shall make a new order for the organism, placing it intermediate between the bacteria on the one side and Microsporidia on the other. Diseases in lower animals due to Microsporidia are frequently characterised by great virulence and well-marked epidemic tendency. Thus it is, for example, in the Pébrine disease of silkworms and in Lymphosporidiosis of brook trout. Singularly enough, these diseases give rise to characteristic lesions in the skin and body-wall analogous, perhaps, to the vesicles and pustules of small-pox. The first appearance of the organism in the human skin is a minute homogeneous spherule, as solid apparently as a sperm head in the cytoplasm of an egg. This enlarges and differentiates into two substances-one destined to give rise to the multiplication elements or gemmules, the other forming an enveloping matrix. The organism increases in size until it is larger than the cell nucleus. gemmules repeat the cycle again and again, thus giving rise to auto-infection of the vaccinia type. The In later stages the gemmules enter the nucleus, where they develop into two kinds of structures; one sort has a central residual mass with peripheral points, the other has a central mass with large surrounding matrix. There is reason to believe that these structures are connected with the sexual generation, the former being a male, the latter possibly a female gametocyte. This point, however, I found impossible to solve, and must leave it for further research. From the structure, which appears like an egg-cell, arises the pan-sporoblast stage. The young sporoblasts appear as exquisitely minute points of deeply staining substance throughout the matrix, which envelops the central mass mentioned above. These increase in size and ultimately give rise to spores. Meantime the nuclear membrane has been ruptured and the sporoblasts are liberated. The spores form in the same way as the gemmules, but differ from these in being hollow spherules five-tenths of a micron in diameter. Spores may be found scattered in the cytoplasm and in the nucleus, but it is only in the latter that they can develop further. In the nucleus they grow into structures somewhat like the primary sporoblasts, but they are readily detected. This, so far as I know, is unique among Protozoa, although analogies are found in other groups of animals. There are thus three modes of auto-infection-viz., gemmule formation, sporulation from the primary sporoblast, and from the secondary sporoblast. All of these together are none too many to account for the rapid spread of the organisms, which in a very few days may infest the entire human skin. 6. Certain Biological Aspects in the General Pathology of Malignant New Growths. By J. A. MURRAY, M.B. From time to time biologists have turned their attention to some of the problems which cancer presents, but their contributions to the subject have not been accepted as final. The limited scope of the individual investigators may well be the principal reason for this want of correlation between the different lines of work. The investigations of the Imperial Cancer Research Fund have been directed by the conviction that it is essential, if progress is to be made, that the facts from widely distinct fields of inquiry should be focussed on the essentials of the problem, and conclusions apparently warranted by one set of observations must be controlled by all the others. The following different lines of inquiry seem to be of importance at present: 1. Pathological-anatomical, including gross anatomy, as well as histological and cytological investigations. 2. Zoological distribution, including ethnological distribution. 3. Statistical investigations-age distribution in correlation with zoological distribution. 4. Experimental investigations. normal and malignant tissue. Transmissibility. Powers of growth of TRANSACTIONS OF SECTION D. Malignant new growths, in common with benign, increase their characteristic As soon as a malignant new parenchyma entirely from their own resources. growth is recognisable as such, it is marked off anatomically and physiologically from its surroundings. This phenomenon, now well established, is sufficiently remarkable when it is borne in mind that, histologically, the independent tissue may be indistinguishable from that among which it takes its origin. To a recognition of this fact is due the acceptance accorded to Cohnheim's hypothesis and all its variants. These variants were introduced because of the necessity that was felt to account for the close dependence of the type of growth on the characters of the surrounding tissue, especially when the latter presents wellmarked differences at different periods (Thiersch, Ribbert). They are all attempts to account for the behaviour of malignant new growths as independent new organisms, and, whatever acceptance we may accord to the various hypotheses, the fact they seek to explain is incontrovertible. In discussing the experimental investigations some reasons for considering these hypotheses as inadequate will be referred to. The cells of malignant new growths increase in number by division. Amitosis certainly occurs, but mitotic division is by far the more common, especially in fully developed tumours. Multipolar mitoses are common, but not universal. The active growth and extension of the malignant tissue, as manifested at the growing surfaces of the malignant new growths we have so far examined, is effected by cell-divisions, which, so far as they are mitotic, conform to the ordinary type met with in early development. Apart from multipolar divisions, the number of chromosomes entering the equatorial plate is found constant in each species, and Many they undergo the ordinary longitudinal splitting. Passing from the growing margin towards the older parts of the growth two sets of changes occur. cells undergo the characteristic histological changes peculiar to the tissue among which the tumour has arisen, while others prepare for further mitosis. In some of these the resulting mitosis is characterised by the presence of bivalent chromosomes (heterotype), in number half that found in the younger parts. From the position of these heterotype mitoses in relation to the growing surface of the tumour in which they occur, they must be regarded as a late phenomenon in the life history of the cells, contemporaneous with the histological differentiation going on around them. We have not found evidence of continued proliferation of the immediate descendants of the heterotypical division, and the analogy of animal spermatogenesis suggests that the heterotype initiates a terminal phase in the life history of the cancer cell as in the spermatocyte. From a consideration of these facts the most divergent conclusions have been drawn. Professor Farmer and his colleagues, who first described the occurrence of heterotypical mitoses in malignant new growths, consider that we have here a transformation of somatic tissue into a kind of reproductive, 'gametoid,' tissue, which, qua its gametoid character, is independent and capable of unlimited further growth. This view of the nature of the change which marks the distinction between somatic tissues and malignant new growths had already been advanced by Beatson as a result of clinical considerations. Against this view the general objection may be raised that, while it would explain the occurrence of heterotypical mitoses in malignant new growths, as regards the powers of growth and self-propagation and independence which they manifest it is no explanation at all. In the vertebrates, where, until now, malignant new growths have alone been found, we have no evidence that gametes, or the tissue which precedes them, possess powers of growth at all comparable to those seen in cancer. The analogies drawn from the vegetable kingdom all concern the interaction of independent organisms, not of different tissues of the same organism. When, however, the attempt is made to attack this problem by experiment, and artificial propagation of reproductive tissue in animals is tried, the results are in no way different from those obtained with other tissues. The power of independent growth is very limited, and it is found that the power of regeneration of which the testis is capable (along with the thyroid) is confined to the stages before differentiation of gametes has commenced. The power of propagation of malignant new growths is much greater. While only possible within animals of the same species as that furnishing the initial growth, it is found that the cells can establish themselves and produce masses of tissue as large as the primary growth in successive animals through long periods. While studying the changes which ensue immediately after transplantation in a tumour of the mouse, we observed nuclear changes which presented a close similarity to a conjugation process. Subsequent observations of an extensive material, embracing over 1,000 tumours of all ages, obtained from three different primary growths, have tended to confirm this interpretation. Thus the same sequence of nuclear changes is again found in later stages, all evidence of its occurrence being wanting in the interval. These observations harmonise very well with the appearances which this tumour presents as it increases in size. Numerous secondary centres of growth are always found around the periphery of older tumours, and these secondary masses may in time outgrow that which preceded them. At once the suggestion arises that the cells which conjugate are those which have passed through a reducing division, but till the complete cycle has been elucidated the thesis outlined above must remain a working hypothesis. It is in harmony with what we know of malignant growths, and renders secondary assumptions unnecessary. The relation it bears to the question of the initiation of the cancer cycle may be emphasised by a short reference to another line of inquiry-that, viz., of the age incidence of malignant new growths. The life cycle of all the higher animals commences by a fertilisation process, on which cell-division ensues, and the rate of this cell-division continually diminishes as life proceeds. Its gradual cessation manifests itself in the onset of old age, and along with this diminishing power of proliferation there is an increasing liability to malignant new growths. The hypothesis outlined above is an attempt to account for the entrance of a new growth cycle without doing violence to what we know of the general course of cellular activity. It involves the assumption that the ordinary tissues of the body in the terminal phases of their growth may undergo changes by which a conjugation process is possible. Whether this process is effected or not would then determine whether a new cycle of growth be initiated and a malignant new growth result. In conclusion, an appeal may be made to working zoologists to be on the alert for malignant new growths and allied conditions in the lower animals. Every observation in this direction has a positive value. So far no case of cancer has been found in reptiles among vertebrates, and none at all in invertebrates. When one considers how frequently cytological studies have been undertaken in the latter, it will be appreciated what importance would attach to the discovery of cancer in lower forms of life. 7. On the Fertilisation of the Egg of the Axolotl. By J. W. JENKINSON, M.A. The most interesting points that have been brought out by a study of fertilisation in this form are as follows: 1. The middle-piece of the spermatozoon, after forming the centre of the sperm-sphere and sperm-aster, completely disappears. 2. At a later stage a centrosome is formed from the sperm-nucleus. divides to give rise to the definitive or cleavage centrosomes. This 3. A watery substance collects in vacuoles in the centre of the sperm-sphere. 4. This suggests that the spermatozoon introduces into the ovum a hygroscopic substance. Experiments have shown that a hygroscopic particle is capable of giving rise to an astral structure in a colloid solution. 8. Some New and Rare Isopoda taken in the British Area.1 By W. M. TATTERSALL, B.Sc. The Isopoda dealt with in the following notes were captured during the cruises of the Helga, the fishery steamer of the Department of Agriculture for Ireland, off the West Coast of Ireland, and also during the operations of the Department at Ballinakill Harbour, co. Galway. The most effective trap for these crustaceans is a tow-net attached to the back of a trawl, in such a position that all the bottom living organisms stirred up by the working of the ground rope of the trawl over the sea-floor find their way into it. Two hauls at 77 miles west of Achill Head (382 fathoms) and 60 miles west of Achill Head (199 fathoms) were particularly productive of new and rare forms. In the latter case the tow-net on the trawl came up full of sand, which on being washed yielded six new species and four species new to Britain. The following species (eight in number) were found to be new to science, four requiring the formation of new genera, while two have been made the types of new families: Typhlotanais proctagon, n. sp. The species new to Britain include: Typhlotanais tenuicornis. Idodrea neglecta. Gnathia stygius. Ischnosoma Greenii, n. sp. Eurycope megalura. Eurycope latirostris. Among rarer species of Isopoda taken may be mentioned: Apseudes hibernicus. Apseudes grossimanus. Idothea metallica. Arcturella dilatata. Paramunna bilobata, and The occurrence of many of these species in the British area is particularly interesting, since most of them have been described by Professor Sass in his great work on Norwegian crustacea. Typhlotanais proctagon differs from all the Norwegian species of the genus by the presence of a spine on the ventrum of the second thoracic segment. In this respect it agrees with T. longimanus, T. Richardii, T. spiniventis, and T. Kerguelenensis. From the three former it differs in having the metasome acutely pointed instead of being evenly rounded. From T. Kerguelenensis, with which it agrees very closely, it differs in the shape of the cephalon, less prominent rostrum, and shorter and stouter chelipeds. Length, 6 mm. Bathycopea typhlops, a new genus in the new family Anciniidæ, the type genus of which is Ancinus, Milne Ed. This form is distinguished by its flat body, small cephalon, absence of eyes, well-marked epimera, the large scythe-like singlebranched uropoda, and the evenly pointed metasome. Length, 5 mm. The family Anciniide is distinguished by having the first two thoracic limbs in the male and the first only in the female subchelate; while the eyes, when present, are situated on top of the head. The family forms a link between the Sphæromida and the Serolidæ. Sphæroma inerme? differs from all the members of the genus in having the mouth organs devoid of the large setæ so characteristic in other species. So little is known of the mouth parts of these species that it is with great reluctance that I put this forward as a new species. The mandible is large and blunt. Full descriptions and figures of these Isopoda will appear in the Reports of the Department of Agriculture for Ireland. |