These facts agree with the suggestion of Fermi that in the living cell the proteins cannot be attacked by the digestive enzymes but relieves us of the necessity of making the monstrous assump­tion of a “living molecule” of proteins as distinct from a “dead” molecule. The difference between life and death is not one between living and dead molecules, but more likely between the excess of synthetic over hydrolytic processes.

In the second chapter we mentioned the interesting idea of Armstrong that when a synthesis is brought about by a digestive enzyme (e. g., maltase) not the original substrate is formed (e. g., maltose) but an isomer, in this case isomaltose; and this isomer is not attacked by the enzyme maltase. We thus get a ra­tional understanding of the statement which Claude Bernard used to make but which remained at his time mysterious: la vie, c’est la créa­tion. During life, when nutritive material is abundant, through the reversible action of certain enzymes, synthetic compounds are formed from the building stones furnished by the blood. These synthetic isomers cannot be hydrolyzed by the enzymes by which they are formed and hence on account of the isomeric structure are immune against destruc­tion. It is not impossible that the increase of the concentra­tion of acid in the cells after death trans­forms the isomers into that form in which they can be digested by the enzymes contained in the cell. Another possibility is that the increase in digestibility brought about by an increase in CH in the cell is due to the hydrating effect of acids on proteins with a subsequent increase in digestibility. Whatever the answer may be, the work done since Claude Bernard has removed that cloud of obscurity which in his days surrounded the prevalence of synthetic action in the living and of disintegra­tion in the dead tissues.

3. We have already referred to the connection between the lack of oxygen and the onset of autolysis and disintegra­tion of tissues in the body. It is of interest that there are cells in which the disintegra­tion under the influence of lack of oxygen is so rapid that it can be followed under the microscope. The writer has observed that certain cells undergo complete irreversible dissolu­tion in a very short time under the influence of lack of oxygen, e. g., the first segmenta­tion cells of the egg of a teleost fish Ctenolabrus.[300]

Fig. 48   Fig. 49
Fig. 50   Fig. 51

When these eggs are deprived of oxygen at the time they reach the eight- or sixteen-cell stage, it can be noticed that the membranes of the blasto­meres are trans­formed into small droplets within half an hour or more, according to the temperature. These droplets begin to flow together, forming larger drops. [Figures 48 to 51 show the successive stages of this process.] When the eggs are exposed to the air in time, segmenta­tion can begin again; but if a slightly longer time is allowed to elapse, the process becomes irreversible and life becomes extinct. Such clear structural changes cannot often be observed in the eggs of other animals under the same condi­tions. Are these changes of structure (apparently liquefac­tion of solid elements) responsible for death under such condi­tions? In order to obtain an answer to this ques­tion, the writer investigated the effect of the lack of oxygen upon the heart-beat of the embryo of the same fish Ctenolabrus. This egg is perfectly transparent and the heart-beat can easily be watched. When these eggs are put into an Engelmann gas chamber and a current of pure hydrogen is sent through, the heart may cease to beat in fifteen or twenty minutes; it stops beating suddenly, before the number of heart-beats has diminished noticeably, and ceases beating before all the free oxygen can have had time to diffuse from the egg. In one case the heart beat ninety times per minute before the hydrogen was sent through; four minutes after the current of hydrogen had passed through the gas chamber, the rate of the heart-beat was eighty-seven per minute, three minutes later it was seventy-seven, and then the beats stopped suddenly. It is hard to believe that this cessa­tion could have been caused by lack of energy. Hydrolytic processes alone could furnish sufficient energy to maintain the heart-beat for some time, even if all the oxygen had been used up. The suddenness of the standstill at a time when the rate had hardly diminished seems to be more easily explained by a sudden collapse of the machine; it might be that liquefac­tion or some other change of structure occurs in the heart or its ganglion cells, comparable to that which we mentioned before. In another fish Fundulus, where the cleavage cells undergo no visible changes in the case of lack of oxygen, the heart of the embryo can continue to beat for about twelve hours in a current of hydrogen. In this case the rate of the heart-beat sinks during the first hour in the hydrogen current from about one hundred to twenty or ten per minute; then it continues to beat at this rate for ten hours or more. In this case one might believe that during the period of steady diminu­tion of the tension of oxygen in the heart (during the first hour), the heart-beat sinks steadily while it keeps up at a low but steady rate as long as the energy for the beat is supplied solely by hydrolytic processes; but there is certainly no change in the physical structure of the cells noticeable in Fundulus, and consequently there is no sudden standstill of the heart.

Budgett has observed that in many infusorians visible changes of structure occur in the case of lack of oxygen[301]; as a rule the membrane of the infusorian bursts or breaks at one point, whereby the liquid contents flow out. Hardesty and the writer found that Paramœcium becomes more strongly vacuolized when deprived of oxygen, and at last bursts. Amœbæ likewise become vacuolized and burst under these condi­tions. Budgett found that a number of poisons, such as potassium cyanide, morphine, quinine, antipyrine, nicotine, and atropine, produce structural changes of the same character as those described for lack of oxygen. As far as KCN is concerned, Schoenbein had already observed that it retards the oxida­tion in the tissues, and Claude Bernard and Geppert confirmed this observa­tion. For the alkaloids, W. S. Young has shown that they are capable of retarding certain processes of autoxida­tion. This accounts for the fact that the above-men­tioned poisons produce changes similar to those observed in the case of lack of oxygen.[302]

The phenomenon of rapid disintegra­tion when deprived of oxygen (or in the presence of KCN) seems to be general as Child[303] has shown in extensive experi­ments. Child has used it to show that younger animals disintegrate more rapidly than older or larger ones, and he uses this fact for a theory of senescence. He connects the more rapid disintegra­tion of the young animal with a greater metabolism.[304] Without wishing to doubt Child’s interesting observa­tions the writer is not quite certain whether the more rapid disintegra­tion of the younger forms is not a result of the fact that the walls of membranes in the young are softer than those of the older animals, and hence are more readily liquefied. Such a difference could be due to mere chemical constitu­tion, e. g., the increase in Ca in the membrane with the increase in age. In old age in man the deposit of Ca in the blood-vessels is a frequent occurrence.

These facts may help us to understand the nature of death and dissolu­tion of the body in higher animals. Death in these animals is due to cessa­tion of oxida­tions, but the surprising fact is that if the oxida­tions have been interrupted but a few minutes life cannot be restored even by artificial respira­tion. This suggests that the respiratory ganglia in the medulla oblongata suffer an irreparable injury or an irreversible change (comparable to that just described in the cells of Ctenolabrus) even when deprived of oxygen for only a short time. As a consequence of the irreversible injury to the medulla the respira­tions cease permanently, the heart-beat must also cease, and gradually the different tissues must undergo the dissolu­tion characteristic of death. While all the cells may be immortal they are only so in the presence of oxygen and the nutritive solu­tion which the circulating blood furnishes. With the proper supply of oxygen cut off they can no longer live.

4. It is an unques­tionable fact that each form has a quite definite dura­tion of life. Unicellular organisms are immortal; but for the higher organisms with sexual reproduc­tion the dura­tion of life is almost as characteristic as any morpho­logical peculiarity of a species. No species can exist unless the natural life of its individuals outlasts the period of sexual maturity; and unless the average dura­tion of life is long enough to allow as many offspring to be brought into the world as will compensate for loss by death. The male bee dies before it is a year old, while the queen may live several years. In a certain species of butterflies, the Psychidæ, the partheno­genetic female lays its eggs while still in the cocoon and then dies without ever leaving the cocoon. The imago of the ephemera leaves the water in the evening, copulates, lets its eggs fall into the water, and is dead the next morning. The imperfect condi­tion of their mandibles and alimentary canal makes them unfit for a long dura­tion of life. The males of the rotifers which are devoid of organs of diges­tion live but a few days.