General Physiology: An Outline of the Science of Life

into chemical relations with the water and its dissolved salts and gases, and thus originated living proteids, i.e., extremely labile compounds, which like other compounds containing the cyanogenradical are distinguished by their tendency toward decomposition and polymerisation, and which form the essential constituents of living substance. This first living substance, which was formed spontaneously out of lifeless substance, was very simple and showed no differentiations. It is very probable that it did not have the morphological value of cells, i.e., that its mass was not yet separated into different substances, such as nucleus and protoplasm, but rather was .homogeneous in all its parts, as Haeckel assumes for his Monera.

Such an idea of the origin of living substance has at present some degree of probability in its favour. It is quite possible that in the future it will be considerably modified in its details. Yet further speculation at present regarding the details is of little value, since the stage upon which living substance made its first appearance and the conditions then prevailing are known so indefinitely. But with living substance already present upon the earth we are upon firmer ground ; for here is the point where the doctrine of descent, founded by Lamarck and Darwin, and developed especially by Haeckel, Weismann and their pupils, comes in and elucidates the farther history of this substance down to the present day.

It would lie outside the purpose of these pages to speak of the whole enormous complex of ideas that led to the founding of the doctrine of descent. It is sufficient to point to the chief factors, the correctness of which no thinking man of science at present doubts. As is well known, the theory of descent teaches that all the multifarious organisms that live to-day and have lived at any time upon the earth's surface are derived in unbroken descent from the first and simplest living substance that originated from lifeless substances, and that, therefore, all organisms stand in true genetic relationship to one another. The continuity of the organic series during historic time needs no special proof; for simple observation shows that every organism is derived from another organism similar to it, that the continuity of descent is never broken. But for the long geological periods elapsing between the appearance of the first organisms and historic time, direct observation is naturally wanting. Here nature has preserved certain records in which are found entered, although more or less incompletely, the history of the evolution of the organic race.

The first record is deciphered by Palaeontology, or the science of fossils. Fossils are the testimony that nature has laid down in the strata of the earth's crust regarding the existence and character of earlier organisms. By the study of fossils palseontology reconstructs to a certain degree the organic world that inhabited the earth's surface at the times when the strata were formed. Thus the ancestry of existing animals and plants is learned. It is seen that existing forms are very similar to those that occur in the latest strata ; that the forms become more dissimilar the farther we go toward the earliest strata ; and that large groups of organisms, which are now considered to be widely separated from one another, have in the older strata common ancestors, which combine in themselves the characteristics of several groups. In the very earliest strata are found lower animals and plants only, no vertebrates and no flowering-plants occur. For every one who is not wedded to a blind, supernatural faith concerning creation, and who does not prefer, in accordance with the biblical account, to think of every form of organism as proceeding by itself from the hand of a personal Creator, there is only .a single natural explanation of all palseontological facts ; namely, that the whole world of organisms, living to-day and living in the past, forms a single, great genealogical tree, the germ of which was the first living substance that appeared upon the earth. This germ developed into a mighty growth with innumerable branches .and twigs and leaves ; its last shoots are seen in the organisms of to-day, its older branches lie buried in the earth. Unfortunately, the pala3ontological record is very imperfect ; for, on the one hand, only a very small fraction of the earth's strata is accessible to investigation — the greater portion of the crust is covered by the .sea ; and, on the other hand, the preservation of organisms is very incomplete, since they can be imbedded only under very definite conditions without becoming destroyed by the impact of the waves, by decomposition, etc.

In fact, organisms that did not possess protecting skeletal parts have been preserved hardly at all, because their delicate bodies disintegrated immediately after death. It thus comes about that in the investigation of the oldest and simplest organisms, which possessed no protecting skeletal parts, the palseontological record fails. Comparative anatomy deals with the second record, which is presented in the homologies of the individual organs of existing organisms. By the dissection of organisms into their smallest parts and by the comparison of individual organs and systems of organs belonging to different groups of organisms, comparative anatomy establishes the fact that as regards their essential organic systems certain groups of organisms agree with others to a certain extent. This fact can be interpreted rationally only by the assumption of a natural relationship between such organisms ; in general such a relationship is closer, the more homologies occur, and the more remote, the more differences are present ; for the homologies can be due only to the fact that iit some time in the early past the organisms had common

ancestors which possessed the features in question. Of course the record of comparative anatomy is also very incomplete, for existing organisms are only the surviving tips of the various twigs of the genealogical tree, between which the other twigs and branches have perished. But here the palseontological record supplements the facts of comparative anatomy up to a certain degree very satisfactorily, by making the dead branches accessible to comparison with the still living ones. An example will illustrate this. Upon comparative - anatomical grounds the conviction was formed that birds stand in very close relationship to reptiles, but forms that might be considered as common ancestors of the two or were close to their ancestors were not known. There was then discovered in the quarries of the lithographic slates of Solenhofen a fossil animal about the size of a pigeon, the now wellknown Arcliceopteryx mac- TUTUS, which possessed the characteristics of both bird and reptile ; it had the jaws of a lizard with teeth, the spinal column of a lizard, and a long lizard-like tail ; but its whole body was covered with bird's feathers, which were impressed upon the rock most delicately (Fig. 134). By this and similar palseontological discoveries the kinship of the birds and the reptiles, which was inferred from comparative anatomy, was very brilliantly confirmed. Similar examples may be cited in great number.

Finally, embryology, or individual germinal development (ontogeny), deals with the third important record of descent. As is well known, the germs of plants and of animals from their simplest condition, the egg-cell, pass through a long series of develop- FIG. 134. — ArchcKopteryx macrums, s. lithographicus. d, Clavicle ; co, coracoid ; h, humerus ; r, radius ; u, ulna ; c, carpus ; sc, scapula ; /. — IV. digits. (After Zittel.) mental stages before they come to resemble the mother from which they are derived.

Since ancestors transmit their characteristics to their descendants, these developmental stages become of extraordinary importance in gaining a knowledge of the ancestral series ; forr since they represent, in gross, forms inherited from ancestors, they indicate, although in rude outline only, the developmental forms that have once appeared in succession in the ancestral series. In other words, the forms that appear in the germinal development or ontogeny of an individual recapitulate in gross the series of forms of the ancestors of the organism in question. This fundamental law of biogenesis, which was founded by Haeckel, and which has been discussed in detail elsewhere,1 enables us, by means of a critical examination of the ontogenetic development of an organism, to reconstruct to a certain degree its phylogenetic descent.

From all these facts of palaeontology, comparative anatomy,, and embryology — for the full appreciation of which reference must be had to the works of Darwin, Gegenbaur, Haeckel and their pupils, which have laid the foundation for an understanding of them — the conclusion must necessarily be drawn that existing organisms are derived in uninterrupted descent from the first living substance that originated from lifeless substance. Moreover, at the same time the path is indicated that has been taken by living substance in its development upon the earth. The phylogenetic research of modern morphology has succeeded in discovering this path in general, and thus reconstructing in its gross outlines the genealogical tree of organisms. Although much opposition was expressed at first to the provisional scheme of genealogy that Haeckel presented thirty years ago as an induction from the facts then known, there are few morphologists now who do not accept Haeckel's idea in its essential points. There now prevails essential agreement regarding the phylogenetic relations of the large groups of organisms, although, as to the smaller groups and the special relations, many far-reaching differences of opinion still exist j the latter will be set aside only gradually and by new discoveries. In accordance with Haeckel's ideas and upon the basis of the present condition of its knowledge, modern morphology has pictured somewhat as follows the genealogical tree of organisms :

AngiospermcK ((Plants having covered seeds, common flowering-plants) (Sea-weeds) (Mushrooms, moulds, etc. ) Protophyta (Unicellular plants) Echinodermata Arthropoda Tunicata Mollusca (Starfishes, sea- (Crabs, in- (Tunicates) (Clams, urchins, etc. ) sects, etc. ) snails, etc. ) From the first living masses, which Haeckei terms Monera, there were developed, by differentiation of the homogeneous substance into nucleus and protoplasm, the first unicellular organisms, Protista. The Protista constitute the group from which, on the one side, plants, and, on the other side, animals have been developed ; they comprise the lowest organisms now living. Even among the Protista a differentiation as to metabolism took place, and they were divided into the Protophyta, i.e., those having plant-metabolism, and the Protozoa, i.e., those having animal-metabolism. The former continued to construct their living substance out of inorganic substances, while the latter simplified their metabolism by employing the organic substance prepared by the former. From the Protophyta are derived all plants (Metaphyta), from the Protozoa all animals (Metazoa), as follows : — From the Protophyta two branches went off, the sea-weeds (Algce) and the moulds, etc. (Fungi). Of these two the former group developed, and from it arose in direct descent the mosses (Miiscinece), from them the ferns (Filicinece), from the ferns the plants that have naked seeds (Gymnospermce), and from the latter, finally, the plants that have covered seeds (Angiospermce). The last group shows the

highest differentiation of the plants. From the Protozoa, on the other hand, arose the Gastrceada, very simple animals consisting of only two layers of cells (entoderm and ectoderm). Probably no representative of this group is now living, but their presence in the genealogical series must necessarily be inferred from the very general appearance of the gastrula-stage in the development of all animals. From the Gastrceada developed on the one side polyps, jelly-fishes, etc. (Ccelenterata), and upon the other side worms ( Vermes). The latter gave origin to four groups comprising respectively star-fishes, sea-urchins, etc. (Echinodermata), crabs, insects, etc. (Arthropoda), tunicates (Tunicata), and clams, snails, etc. (Mollusca). Of these the tunicates became the progenitors of the back-boned animals ( Vertebrata), the most widely differentiated representatives of the animal kingdom. The present living organisms form merely the last shoots of all the branches of this great genealogical tree.

A glance over the racial development of organisms from their first appearance down to the present time shows that living substance has undergone in the course of the earth's development a remarkable change in form and organisation ; in these respects existing organisms are widely differentiated in very different directions. Darwin's theory of selection has afforded a natural explanation of this phenomenon. This theory proceeds from the fact that all individuals of the same species, even descendants from the same pair of parents, differ from one another more or less markedly. This phenomenon is known as individual variability, and is the result partly of sexual intermixture (Weismann's amphimixis) and partly of the action of various external influences upon the germ-plasm of the individual embryos, whether within or without the maternal organism. Of these more or less different individuals of the same generation Darwin shows that in the struggle for existence only those continue to live that are best fitted to the external conditions of life, while those that are less fitted perish as a result of the competition with the former. Thus, only those that are best adapted to the existing external conditions can reproduce and transmit their characteristics to their descendants. In this survival, in this selection of the fitter individuals, Lies the natural selection of Darwin; and it is evident that with the continuance of the process organisms must become adapted to existing vital conditions very perfectly. Hence the form, the organisation, and, in general, all the characteristics of living substance are in the closest correlation with the external conditions upon the earth's surface ; if these change, the characteristics of organisms must correspondingly change.

But it is a question whether, in the course of time, natural selection is the sole factor that causes organisms to change. Adaptation to external conditions as a result of selection presupposes a continual inheritance of innate characteristics, and Weismann ('92, 1) holds the view that the inheritance of innate characteristics alone comes into the question of change in the organic world. Since Darwin believed that acquired characteristics also are transmitted, Weismann, as the defender of the onesided theory of selection, is, in a certain sense, more Darwinian than Darwin himself. Others, such as Haeckel ('66), Eimer ('88), and Herbert Spencer ('93), are also of the opinion that the inheritance of such characteristics as are acquired during the individual life is of great importance in the transformation of organisms. Naturally there always arises here the question whether these characteristics are properly adapted to external conditions or not. If not, they likewise are soon set aside by selection in the struggle for existence. But at the present time the question whether only innate or also acquired characteristics are inherited, constitutes the point of chief interest for those who theorise upon heredity : and, in spite of much discussion, it still waits for a definitive answer.1

If, finally, a brief examination be made of the nature of the changes that living substance has undergone from its origin down to the present, the fact appears that it has developed from simple to constantly more complex forms and organisation. The result is that the most complex organisms occur at the present time, being represented by the flowering-plants and the vertebrates, in which special parts have become widely differentiated for the exercise of very special occupations. It has frequently been said that in the developmental series of organisms from the earliest beginnings down to the present there may be seen a continual advance — a progressive perfecting. This idea embraces an error which it was the whole endeavour of the Darwinian theory to avoid, viz., that of teleology. The conception of advance, of perfecting, involves a goal toward which the advance is directed. Without this it is an empty conception. In reality, however, there does not exist in the development of organisms a predestined goal toward which the development is striving any more than in any chemical reaction. Organisms can only follow, and must follow in a definite direction, when the proper external conditions are present. Changes in them are dependent solely upon changes in their environment. The employment, therefore, of the idea of advance or perfecting is evidence merely of an anthropocentric standpoint ; we introduce ourselves into the development as the goal. For whatever reason this is done, the goal is an artificial thing which does not exist in nature ; the assumption that mankind is more perfect than an amosba is not justified by reality. It is simply a conventionality to call development a perfecting.

Nature itself has no goal to strive for, its method is eternal development, i.e., change without end. To draw, now, the final conclusions from the above discussion, the fact stands out clearly and distinctly that life from its beginning on has been dependent upon the external conditions of the earth's surface. In a mathematical sense, life is a function of the earth's development. Living substance could not exist while the earth was a molten sphere without a solid, cool crust ; it was obliged to appear with the same inevitable necessity as a chemical combination, when the necessary conditions were given ; and it was obliged to change its form and its composition in the same measure as the external conditions of life changed in the course of the earth's development. It is only a portion of the earth's matter. The combination of this matter into living substance was as much the necessary product of the earth's development as was the origin of water. It was an inevitable result of the progressive cooling of the masses that formed the earth's crust. Likewise, the chemical, physical and morphological characteristics of existing living substance are the necessary result of the influence of the external conditions of life upon the internal relations of past living substance. Internal and external vital conditions are inseparably correlated, and the expression of this correlation is life.

Our consideration of vital conditions culminated in the fact that vital phenomena not only can exist, but must appear with the same inevitable necessity as every other natural phenomenon, when a certain complex of conditions is fulfilled. If these conditions are wanting, life is wanting. The appearance of life upon the earth was one consequence of this fact. Another consequence, which is now to be considered, was the development of death. If one or more of the special vital conditions under which an organism exists fail, vital phenomena cease, life comes to a standstill. Excepting the few cases of apparent death, this standstill is always real death. But, as has already been seen,1 death never appears instantaneously. There is no sharp limit separating life and death, there is rather a gradual transition between them ; in other words, death undergoes development. Normal life upon the one

hand, and death upon the other, are merely the remote end-stages in this development, and are united to one another by an uninterrupted series of intermediate stages. The two endstages may be easily and sharply distinguished, but it is impossible to draw a sharp line at the place where life ceases and death begins. Hence this transition from life to death is termed necrobiosis, a word that was introduced into pathology by K. H. Schultz and Virchow. Virchow ('71) distinguishes between necrobiosis and necrosis by means of external characters, speaking of necrobiosis when the original form of the part in question is completely destroyed and done away with, and of necrosis when it is still retained in death. But. however practicable this external difference may be in the judgment of gross relations, of whole organs or tissues, it has little importance theoretically, for whether the end-result assumes this or that form frequently depends upon wholly accessory matters. If, e.g., a cell has a solid wall, its form long remains, although the protoplasmic body may long since have perished ; but if its protoplasm is naked, the cell usually disintegrates into a formless mass of granules ; nevertheless, the essence of the process that leads to death may be the same in the two cases. Hence it seems advantageous to lay aside this distinction and so to extend the conception of necrobiosis that it may include also the so-called necrotic processes. There is then understood by necrobiosis those processes that, beginning with an incurable lesion of the noi*mal life, leads slowly or rapidly to unavoidable death. The frequent synonymous conception of degeneration has the disadvantage that it has more than one significance and is employed for many very different phenomena.

The phenomena of necrobiosis introduce a subject which, on account of its enormous practical importance, has been developed as an independent science and has assumed large proportions ;. this is pathology, the science of diseases. The following considerations will, therefore, largely pertain to this subject, and an endeavour will be made to analyse the death-process. Since the cell is the proper seat of life, it must be the object, of study in the investigation of necrobiosis as in that of vital phenomena. The death of compound organisms with their widely differentiated organs and tissues depends simply upon the death of the individual cells composing the cell-community. But the phenomena that lead to death are very different in the individual forms of cells. This depends partly upon the condition of the living substance that characterises each form, and partly upon the nature of the causes that lead to the death of the cell. It is, therefore, evident that necrobiotic phenomena must be very manifold. Nevertheless, they can be brought into two great groups, which differ fundamentally from one another. In one group the normal vital processes drop out gradually without under-

going an essential change ; these phenomena may be termed histolytic processes. In the other group the normal vital processes are turned into a perverse course by the fatal lesion, and degenerate before they come to a complete standstill. These are termed metamorphic processes. The simplest forms of the histolytic processes are the atrophies. They are mostly chronic processes, and consist in the gradual constant decrease in extent and final complete cessation of the ascending phase of the metabolism of the cell in question, that is, of the processes that lead to the construction and regeneration of living substance. The result is that the living substance, continually undergoing decomposition in a certain measure, loses in volume constantly ; the cell becomes constantly smaller, until finally the remnant, having come to an extreme, disintegrates —technically speaking, the cell or the tissue " atrophies."

Cases of atrophy of an organ or tissue are wide-spread in the organic world, and play a great role both in the normal development of animals and in pathological conditions. Among those that appear in the development of the normal organism and are especially well known are the phenomena of histolysis or degeneration of embryonic organs, which are particularly characteristic of animals that have a pronounced metamorphosis or larval development. These histolytic processes have been carefully followed recently in the atrophying tail of the tadpole of the frog by Looss ('89). In its essentials histolysis follows a corresponding course in different forms of cells. There is noticeable first a loosening of the cementsubstance that unites the cells together into the tissue, so that the cells adhere to one another less closely. During this a visible change begins in the protoplasm. " The cell-substance gives up its normal characteristic structure. The spongioplasm, present originally in the form of a more or less pronounced spongy framework and usually capable of staining intensely, draws itself together, the individual strands become thicker, and, finally, the whole disintegrates into a larger or smaller number of spherical droplets, which lie within the hyaloplasm. The latter stains less or not at all, and has likewise come together into a homogeneous mass." The ground-substance in which the globules lie first begins to dissolve, and later the globules themselves become liquefied. Thus, finally, of the whole protoplasm there remain only a few insoluble granules, and these are devoured by the leucocytes which creep about as phagocytes in all tissues. The nucleus of the cell usually resists destruction considerably longer, but finally becomes the victim of a similar process. Its ground-substance disappears very

soon ; the chromatic substance and the nuclear membrane gradually shrink together and disintegrate into single fragments, which likewise are finally dissolved. The muscle -fibres, though in other respects very different, behave similarly. The individual fibrillse swell and become cemented to one another. At the same time FIG. 135.— Histolysis of muscle-fibres in the tail of the larva of the -frog. (After Looss.) the isotropic and the anisotropic substances begin to mingle together, so that the cross-striation gradually disappears. The double refraction of the anisotropic disks also fades away. At the same time the fibres disintegrate into small round fragments, which finally undergo solution (Fig. 135). The processes of histolysis go on in a wholly analogous manner in most other cases, e.g., in the degeneration of the larval organs of insects, the muscles of the salmon, and the thymus-glands of human beings. But from the investigations of Metschnikoff ('83), Kowalevsky ('85, '87), and others, it appears that in many insects, especially in the fly-larva, where the degeneration of the larval tissue proceeds uncommonly

FIG. 136.— Fragments of muscle-fibres in the metamorphosis of the fly-larva, destroyed by leucocytes. The darker, granular cells are the leucocytes. (After Kowalevsky.) rapidly, the histolysis is performed chiefly by the leucocytes, which as phagocytes devour the tissue-cells that have not yet disintegrated (Fig. 136). It must be supposed that here also the inauguration of histolysis proceeds from the tissue-cells themselves, and that the leucocytes devour the cells that are already beginning to atrophy.

The whole difference lies in the fact, as has been set forth by Korotneff ('92), that where a very rapid disappearance of the tissue is concerned, the leucocytes exercise greater activity and begin their work earlier. Among the atrophies in normal life belong, further, the phenomena of senile atrophy, which consists in a very slow and constantly progressive degeneration of the various tissues, and is never wanting in extreme old age. Next to the normal atrophies are the pathological ones, which appear in the organism when diseases have created the proper conditions for them. Thus, e.g., in human beings the muscles of the leg atrophy when, as a result of disease, the knee-joint has become ossified and immovable. Such atrophies, which occur as a result of disuse of the organ, are termed, simply, atrophies from disuse. In these pathological atrophies the processes are, in

FIG. 137. — Degeneration of leucocytes in acute leukaemia. 7 and //, Normal leucocytes ; the dark mass is the cell-nucleus, the clear border, the protoplasm. /// — VII, Stages of the dissolution. (After Gumprecht.) general, the same as in normal ones; nevertheless, at times remarkable phenomena appear. Thus, in muscles that have atrophied because of disease, a very great increase of nuclei is frequently found, while Loosswas able to determine with certainty that in the muscle-atrophy of the histolytic tail of the tadpole the nuclei were neither increased nor diminished. Further, the tissues atrophying because of disease are at first, as a rule, much more solid and compact than those that undergo normal histolysis — a circumstance that is perhaps based upon the considerably longer duration of the pathological atrophy, during which the dissolved masses have more time to be discharged. But these are all special, accessory factors.

The degeneration of leucocytes has recently been followed in detail especially by Gumprecht ('96) in acute leukaemia. It is interesting, since the dissolution of the nucleus takes place in a very simple manner. The nuclear membrane disappears, the contents of the nucleus mix with the protoplasm, the chromatic substance becomes gradually paler, until the whole leucocyte becomes a homogeneous mass, which disintegrates with swelling and formation of vacuoles (Fig. 137).

To the atrophies may be added a series of death-processes, which, although they have little similarity to one another, are grouped in pathology under the common name of necroses.1 In general they have a more acute course than atrophies. Among the various necrotic processes several important forms can be distinguished, which are characterised by definite peculiarities. One of these is mummification or dry gangrene. In this the tissue-cells shrink into solid, leather-like masses on account of a loss of liquid, so that when the process has reached its end the tissues appear dry, hard and friable. Mummification occurs normally in the drying-up of the remnant of the umbilical cord of the new-born child; in pathological conditions, as after burning or freezing the ends of the fingers and of the toes ; particularly in old age ; and also in the dryingup of embryos that develop in the abdominal cavity of the animal or the human being instead of in the uterus and, being incapable of birth, die within the body of the mother. Such embryos assume gradually a hard, mummylike consistency, because the liquid contained in them is absorbed by the mother's body. A second important form of necrosis is coagulation-necrosis, first investigated in detail by Weigert (75, 77, 78, '80), which consists in the coagulation of the proteids of the tissue-cells in question. With the coagulation-necroses may be classed the usual rigor of dying muscles, which along with gradual contraction transforms the muscles into stiff organs and causes the rigidity of corpses. Weigert himself does not allow this classification, regarding the co-operation of lymph as essential to the occurrence of the coagulation-necrosis. But the process in rigor mortis, although transitory, is the same in principle ; for the myosin, the proteid that is characteristic of and contained in solution in the living muscle, coagulates in dying and thus produces the stiffen- 1 Of. Cohnheim ('77— '80) and Ziegier ('95).

FIG. 138.— Waxy degeneration of muscle in typhoid fever, a, Normal cross-striated ing ; as a result of other transformations in the muscle the rigor passes away, this process being accompanied by muscular relaxation. A typical coagulation-necrosis in Weigert's sense occurs in muscle under pathological conditions, especially in connection with fevers, such as typhoid ; this is the so-called -waxy 'degeneration, which consists in a coagulation of the muscle-substance with loss of its cross-striation and a separation into waxy-appearing flakes (Fig. 138). Similar coagulation-processes occur in other tissuecells, especially in active inflammations of the mucous membranes, as in pharyngeal diphtheria. Finally, among the coagulationnecroses in the wider sense there can be classed the phenomena of cell-death that appear when, for the purpose of

FIG. 139. — Liquefaction at the edge of a blister caused by burning, a, Horny layer of the epidermis ; b, rete Malpighii of the epidermis ; c, normal papilla; of the dermis ; d, cells swollen and already partly liquefied ; e, partly normal cells ; /, liquefied mass ; g and h, swollen cells with nuclei destroyed ; i, sunken papillae ; £, coagulated exudation. (After Ziegler.) anatomical or histological preservation, living tissue is placed in liquids that cause coagulation, such as mineral acids, alcohol, sublimate, etc. These are the most acute cases of cell-death, and for this reason these liquids are especially well-fitted for killing and preserving. By their application the living cell is killed suddenly ; it thus has not time to undergo extensive change, but in a moment is fixed in a condition very similar to that of life. In a third form of necrosis, liquefaction, the tissue-cells become completely liquefied, their protoplasm disintegrating into a granular detritus and the nuclei and cell-boundaries dissolving until the tissue is changed into a thickish liquid. Such softenings occur especially in the formation of blisters after burning (Fig. 139), and frequently combine with coagulation-pheno-

mena. Not rarely, different forms of necrosis occur combined, and they become complicated especially by secondary factors, such as putrefaction. The latter is the case with moist gangrene, decay, etc., all of which are produced by the action of putrefactive bacteria upon necrobiotic tissue, and some of which represent postmortem phenomena. Further, certain other forms of necrosis have been more or less identified by pathology, but these pathological classes are distinguished much more by the macroscopic phenomena of the end-result than by the microscopic events in the cell itself. The former naturally depend upon various kinds of accessory circumstances that are not immediately conditioned by the pure phenomena of cell-death.

Finally, one more series of phenomena may be added to the atrophies and necroses ; these accompany the death of cells living in aqueous media and are wide-spread among organisms ; they are the phenomena of granular disintegration.1 The one thing held in common by all kinds of granular disintegration is that at the end of the process the cell in question forms a more or less loosely coherent mass of individual granules. Granular disintegration can be observed most easily in many In- fusoria, when their protoplasm is especially rich in water. This is the case in the large, cylindrical Spirostomum ambiguum which has a soft, superficial layer of exoplasm. If such Infusoria be wounded by being cut into two pieces under the microscope, it happens very frequently that the pieces disintegrate away regularly from the surface of the wound. Death can be followed by the eye, and its course resembles that of a spark that passes over a fuse and leaves behind it merely a loose mass of ashes. It creeps over the whole body, seizing upon particle after particle, surprising cilium after cilium in normal activity, and forcing them directly from active life into a standstill, until that which a moment before was in active motion is changed into a dead mass of granules (Fig. 140).