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In some Ephemerida, which supply good cases of natural death, the end comes after a few hours of adult life without any sign of degeneration of the organs. As in others (Chloë), life lasts for several days without food having been taken, it is clear that inanition is not the cause of the swift arrival of death in the first set. It is much more probable that the natural death is due to an auto-intoxication which takes effect at different intervals of time in different circumstances.1

In the higher animals such as vertebrates the conditions are less favourable than in the case of insects for the investigation of the causes of natural death. Vertebrates have always well-developed organs of digestion and so live a relatively longer time and encounter a greater number of chances of accident, with the result that in most cases death comes from external accidental causes. Vertebrates usually perish from hunger or cold, or are devoured by their enemies or killed by the attacks of parasites or diseases. There remains only the human race amongst the more highly developed animals, in which to study the onset of natural death. And in the human race cases which may be designated as natural are extremely rare.

1 See The Nature of Man.

III

NATURAL DEATH AMONGST HUMAN BEINGS

Natural death in the aged-Analogy of natural death and
sleep-Theories of sleep-Ponogenes-The instinct of sleep
-The instinct of natural death-Replies to critics-Agree-
able sensation at the approach of death

THE death of old people, which has often been described as natural death, is in most cases due to infectious diseases, particularly pneumonia (which is extremely dangerous) or to attacks of apoplexy. True natural death must be very rare in the human race. Demange1 has described it as follows:-" Arrived at extreme old age, and still preserving the last flickers of an expiring intelligence, the old man feels weakness gaining on him from day to day. His limbs refuse to obey his will, the skin becomes insensitive, dry, and cold; the extremities lose their warmth; the face is thin; the eyes hollow and the sight weak; speech dies out on his lips which remain open; life quits the old man from the circumference towards the centre; breathing grows laboured, and at last the heart stops beating. The old man passes away quietly, seeming to fall asleep for the last time." Such is the course of what properly speaking is natural death.

The natural death of human beings cannot be regarded as due to exhaustion from reproduction or from inanition,

1 Étude clinique sur la vieillesse, Paris, 1886, p. 145.

as in the case of Monstrilla. It is much more likely that it is due to an auto-intoxication of the organism. The close analogy between natural death and sleep supports this view, as it is very probable that sleep is due to poisoning by the products of organic activity.

It is more than fifty years since sleep was explained as the result of auto-intoxication. Obersteiner, Binz, Preyer, and Errera are among the competent men of science who have taken this view. The first two attributed sleep to an accumulation in the brain of the products of exhaustion which are carried away by the blood during repose. The attempt has been made even to discover the nature of these narcotic substances. Some investigators think that an acid, produced during the activity of the organs, is stored up in quantities that cannot be tolerated. During sleep, the organism gets rid of this excess of acid.

Preyer tried to put the problem upon a more exact basis by the theory that the activity of all the organs gives rise to substances which he called ponogenes and which he regarded as producing the sensation of fatigue. According to him these substances accumulate during the waking hours, and are destroyed by oxidation during sleep. Preyer thinks that lactic acid is the most important of the ponogenes, and lays stress on its narcotic effect. If his theory were correct, there would be a remarkable analogy between the auto-intoxication by lactic acid in the cases of man and animals, and the case of bacteria which produce the same acid and the fermenting activity of which is arrested as the acid accumulates. Just as sleep may be transformed to natural death, so also the arrest of lactic fermentation may be followed by the death of the bacteria which form the acid.

1 Revue scientifique, 1877, p. 1173.

So far, however, there has been no confirmation of Preyer's theory. Errera1 has brought forward against it another theory according to which the cause of sleep is not acid products, but certain alkaline substances described by M. Armand Gautier under the name of leucomaines. Gautier laid down that these substances act on the nervous centres and produce fatigue and sleepiness. According to Errera they might very well be the cause of sleep, as that comes on at a time when there is the greatest accumulation of these leucomaines in the body. He thinks that their action in producing sleep is a direct intoxication of the nerve centres. During sleep they are removed, and the disturbance which was produced in the organism is arrested.

If it were possible to accept Errera's theory, a kind of analogy could be established between sleep and natural death on the one hand, and the arrest of development and death of yeast grown in nitrogenous media on the other hand, because in the latter case the poisoning is produced by an alkaline salt of ammonia. It must be confessed, however, that the actual state of our knowledge does not allow of a definite view of the real mechanism of the sleepproducing intoxication. Our ideas regarding leucomaines in general are still incomplete, and, recently, one of them, adrenaline, the product of the supra-renal capsules, has been investigated. Adrenaline is an alkaloid which is produced in the supra-renal bodies and is discharged into the blood. It has the power of contracting arteries strongly, and has been used to control blood-pressure. When it is given in large quantities or in frequent doses, it acts as a true poison, whilst, in small doses, it produces anæmia of the organs and has a special influence on the nervous

1 Revue scientifique, 1887, 2nd part, p. 105.

2 Gabriel Bertrand, Annales de l'Institut Pasteur, 1904, p. 672.

centres. Dr. Zeigan1 has shown that a milligramme of adrenaline, mixed with five grammes of normal salt solution injected into the brain of cats, produces a soporific action. "About a minute after the injection, the animal appears to be plunged into deep sleep which lasts from 30 to 50 minutes. During this time, the sensitiveness of the animal has completely ceased throughout the body, and for some time after that it is much decreased. When they awake the animals seem to have been drunk with sleep for some time." Sleep is generally associated with anæmia of the brain, and as adrenaline can actually produce such anæmia, it might be supposed that this narcotic substance is the most important of the organic products which give rise to sleep. Against this hypothesis, however, some weight must be given to recent investigations on fatigue and its

causes.

Each stage in the advance of knowledge has had its influence on the study of the interesting and complex problem of sleep. When it was thought that alkaloids (ptomaines) were of great importance in infectious diseases, it was attempted to explain sleep as due to the action of similar bodies. Now, when we believe that in such diseases the chief part is played by poisons of extremely complex chemical composition, the attempt is made to explain fatigue and sleep by similar bodies.

Weichardt has recently made the best known investigations in this direction. This young man maintains with ardour the view that during the activity of organs there is an accumulation of special materials which are neither organic acids nor leucomaines, but which are much more like the toxic products of pathogenic bacteria.

1 Therapeutische Monatshefte, 1904, p. 193.

2 Münchener medicinische Wochenschrift, 1904, No. 1; Verhandlungen der physiologischen Gesellschaft zu Berlin, Dec. 5th, 1904.

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