CHAPTER III.PHYSICAL AND CHEMICAL CHARACTERS OF CELLULAR DEATH. NECROBIOSIS. GROWING OLD.
Characteristic of elementary life—Changes produced by death in the composition and the death of the cell—Schlemm; Loew; Bokorny; Pflüger; A. Gautier; Duclaux—The processive character of death—Accidental death—Necrobiosis—Atrophy—Degeneration—So-called natural death—Senescence—Metchnikoff’s theory of senescence—Objections.
Elementary death is nothing but the suppression in the anatomical elements of all the phenomena of vitality.
Characteristics of Elementary Life.—The characteristic features of elementary life have been sufficiently fixed by science. First of all, there ismorphological unity. All the living elements have an identical morphological composition. That is to say that life is only accomplished and sustained in all its fulness in organic units possessing the anatomical constitution of the cell, with its cytoplasm and its nucleus, constituted on the classical type. In the second place, there ischemical unity. The constituent matter, the matter of which the cell is built up, diverges but little from a chemical type—a proteid complex, with a hexonic nucleus, and from a physical model which is an emulsion of granulous, immiscible liquids, of different viscosities. The third character consists inthe possession of aspecific formacquired, preserved, and repaired by the element. The fourth character, and perhaps the most essential of all, isthe property of growthornutritionwith its consequence, namely, a relation of exchanges with the external medium, exchanges in which oxygen plays considerable part. Finally, there is a last property, that ofreproduction, which in a certain measure is a necessary consequence of the preceding,—i.e., of growth.
These five vital characters of the elements are most in evidence in cells living in isolation, in microscopical beings formed of a single cell, protophytes and protozoa. But we find them also in the associations formed by the cells among one another—i.e., in ordinary plants and animals, multicellular complexes, called for this reason metaphytes and metazoa. Free or associated, the anatomical elements behave in the same way—feed, grow, breathe, digest in the same manner. As a matter of fact, the grouping of the cells, the relations, proximity and contiguity, which they assume, introduce some variants into the expression of the common phenomena; but these slight differences cannot disguise the essential community of the vital processes.
The majority of physiologists, following Claude Bernard, admit as valent and convincing the proof that the illustrious experimenter furnished of this unity of the vital processes. There are, however, a few voices crying in the wilderness. M. Le Dantec is one. In his new theory of life he amplifies and exalts the differences which exist between the elementary life of the proteids and the associated life of the metazoa. In them he can see nothing but contrasts and deviations.
If this is elementary life, let us ask what iselementary death—i.e., the death of the cell. And in this connection let us ask the questions which we have to examine in the case of animals high in organization, and of man himself. What are the characteristics of elementary death? When the cell dies, is its death preceded by a growing old or senescence? What are the preliminary signs and the acknowledged symptoms?
Changes Produced by Death.—The state of death is only truly realized when the fundamental properties of living matter enumerated above have entirely disappeared. We must follow step by step this disappearance in all the anatomical elements of the metazoan.
Now the properties of the cell are connected with the physical and chemical organization of living matter. For them to disappear entirely, this organization must be destroyed as far as all that is essential in it is concerned. We cannot admit with the vitalists that there is any material difference between the dead and the living, and that only an immaterial principle which has escaped into the air distinguishes the corpse from the animated being. In fact, the external configuration may be almost preserved, and the corpse may bear the aspect and the forms of the preceding state. But this appearance is deceptive. Something in reality has changed. The structure, the chemical composition of the living substance, have undergone essential changes. What are these changes?
Physical Changes.—Certain physiologists have endeavoured to determine them. Klemm, a botanist, pointed out in 1895 the physical changes which characterize the death of vegetable cells—loss ofturgescence, fragmentation of the protoplasm, the formation of granules, and the appearance of vacuoles.
Chemical Changes.—O. Loew and Bokorny laid great stress in 1886 and 1896 on the chemical changes. The living protoplasm according to them is an unstable proteid compound. A slight change would detach from the albuminoid molecule a nucleus with the function of aldehyde, and at the same time would transform an amido-group into an amido-group. This would suffice for the transition of the protoplasm from the living to the dead state. This theory is based on the fact that the compounds which exercise a toxic action on the living cell, without acting chemically on the dead albumin, are easily fixed by the aldehydes; and on the fact that many of them, which attack simultaneously the living albuminoids and the dead albumin, easily combine with the amido-group.
E. Pflüger, a celebrated German scientist, has considered living matter as an albumin spontaneously decomposable, the essential nucleus of which is formed by cyanogen. Its active instability would be due to the penetration into the molecule of the oxygen which fixes on the carbon and separates it from the nitrogen. Armand Gautier has not confirmed this view. Duclaux (1898) has stated that the difference between the living and the dead albumin would be of a stereochemical order.
Progressive Character of Death. Accidental Death.—We have seen that in general the disappearance of the characteristics of vitality is not instantaneous, at least in the natural course of things, in complex organisms. It is the end of a more or less rapid process. But death is not instantaneous in the isolated anatomical element any more than it is in the protozoan orprotophyte. We must have recourse to very violent devices of destruction to kill the cell at a blow, to leave absolutely nothing of its organization existing. The protoplasm of yeast when violently crushed by Büchner still possessed the power of secreting soluble ferments. A powerful action, a very high temperature, is necessary to obtain the result.A fortiori, the difficulty increases in the case of complex organisms, all of whose living elements cannot be attacked at the same moment by the destructive cause. A mechanical action, capable of destroying at one blow all the living parts of a complex being, of an animal, of a plant, must be of almost inconceivable power. The blow of a Nasmyth hammer would not be strong enough.
The chemical alteration produced by a very toxic substance distributed throughout the blood, and thus brought into contact with each element, would produce a disorganization which, however rapid it were, could not be called instantaneous. And the same holds good of physical agents.
But these are not the processes of nature under normal circumstances. They are accidents or devices. We shall leave on one side their consideration and we shall only deal here with the natural processes of the organism.
Imagine it placed in a medium appropriate to its needs and following out without intervening complications the evolution assigned to it by its constitution. Experiment tells us that this natural evolution in every case known to us ends in death. Death supervenes sooner or later. For beings higher in organization, which we can bring into closer and closer resemblance to man, we find that they die ofdisease, by accident, or of old age. And as disease is an accident, we may naturally ask if what we call old age is not also a disease.
However that may be, the mortal process, being never instantaneous, has a duration, a beginning, a development, an end—in a word, a history. It constitutes an intermediary phase between perfect life and certain death.
Necrobiosis.Atrophy.Degeneration.—The process according to the circumstances may be shortened or prolonged. When death is the result of violence events are precipitated. The physical and chemical transformations of the living matter constitute a kind of acute alteration called by Schultze and Virchownecrobiosis. According to the pathologists, there are two kinds ofnecrobiosis:—that bydestruction, bysimple atrophy, which causes the anatomical elements to disappear gradually without undergoing appreciable modifications; andnecrobiosis by degeneration, which transforms the protoplasm into fatty matter into calcareous matter, into granulations (fatty degeneration, calcification, granulous degeneration). There is no disagreement as to the causes of this necrobiosis. They are always accidental; they originate in external circumstances:—the insufficiency of the alimentary materials, of water, of oxygen; the presence in the medium of real poisons destroying the organized matter; the violent intervention of physical agents, heat, electricity; the reflex on the composition of the cellular atmosphere of a violent attack on some essential organ, the heart, the lungs, the kidneys.
Senescence.Old Age.—In a second category we must place the mortal processes, slow in their movement, in which we cannot see the intervention of clearly accidental and abnormal disturbing agents. Death appears to be the termination of a breaking-up proceeding by insensible degrees in consequence of the progressive accumulation of very small inappreciable perturbations. This slow breaking up is adequately expressed by the term—growing old, or senescence. The alterations by which it is betrayed in the cell are especiallyatrophic, but they are also accompanied, however, by different forms of degeneration. An extremely important question arises on this subject, and that is whether the phenomena of senility have their cause in the cell itself, if they are inevitably found in its organization, and therefore if old age and death are natural and necessary phenomena. Or, on the other hand, should we consider them as due to a progressive alteration of the medium, the character of which would be accidental although frequent or habitual? This, in a word, is the problem which has so often engaged the attention of philosophical biologists. Are old age and death natural and inevitable phenomena?
The recent experiments of Loeb and Calkins, and all similar observations, tend to attribute to the phenomenon of growing old the character of a remediable accident. But the remedy has not been found, and the animal finally succumbs to these slow transformations of its anatomical elements. We then say that itdies of old age.
Metchnikoff’s Theory of Senescence. Objections.—Metchnikoff has proposed a theory of the mechanism of this general senescence. The elements of the conjunctive tissue, phagocytes, macrophages, which exist everywhere around the specialized and higheranatomical elements would destroy and devour them as soon as their vitality diminishes, and would take their place. In the brain, for example, it would be the phagocytes which, attacking the nervous cellules, would disorganize the higher elements, incapable of defending themselves. This substitution of the conjunctive tissue, which only possesses vegetative properties of a low order, for the nervous tissues, which possesses very high vegetative properties, results in an evident breaking-up. The gross element of violent and energetic vitality stifles the refined and higher element.
This expulsion is a very real fact. It constitutes what is called senile sclerosis. But the activerôleattributed to it by Metchnikoff in the process of degeneration is not so certain. An expert observer in the microscopic study of the nervous system, M. Marinesco, does not accept this interpretation as far as the senescence of the elements of the brain is concerned. Diminution of the cell, the decrease in the number of its stainable granulations, chromatolysis, the formation of inert, pigmented substances—all these phenomena which characterize the breaking-up of the cerebral cells would be accomplished, according to this observer, without the intervention of the conjunctive elements, the phagocytes.
The characteristic of extensive and progressive process presented by death necessitates in a complex organism, which is a prey to it, the existence side by side of living and dead cells. Similarly, in the organism which is growing old, there are young elements and elements of every age side by side with senile elements. As long as the disorganization of the last has not gone too far, they may be rejuvenated.All we have to do is to restore to them an appropriate ambient medium. The whole question is one of knowing and being able to realize, for this or that part which we wish to reanimate and to rejuvenate, the very special or very delicate conditions that this medium must fulfil. As we have said, success is attained in this respect as far as the heart is concerned, and this is why we are able to reanimate and to revive the heart of a dead man. It is hoped that ideas along these lines will extend with the progress of physiology.
After this sketch of the conditions and of the varieties of cellular death we must return to the essential problem which is engaging the curiosity of biologists and philosophers. Is death unavoidable, inevitable? Is it the necessary consequence of life itself, the inevitable issue, the inevitable end?
There are two ways of endeavouring to solve this question of the inevitability of death. The first is to examine popular observation, practised, so to speak, unintelligently and without special precautions. The second is to analyze everything we know relative to the conditions of elementary life.