PHYSIOLOGY OF SLEEP—LEGENDRE. 601 
consider them as the causes of sleep, and, in fact, they appear very 
often to be the consequences rather than the causes. 
But sleep is an instinct of defense, of protection. Against what 
does it protect? Will not the suppression of sleep, insomnia, show 
us the reason for that instinct, by exaggerating its causes; may we 
not the better see what belongs to the domain of physiology? We 
have been led to keep animals awake so as to study what happens 
to them under these conditions. The first difficulty was to prolong 
wakefulness with the least fatigue; in fact, the effects of fatigue 
might hide or disturb the very conditions that we may wish to study. 
Various experiments with severe and prolonged work, such as observa- 
tions of deer driven at the course, have enabled us to distinguish the 
effects of fatigue from those of insomnia; and we have succeeded in 
preventing some dogs from sleeping while tiring them as little as 
possible. 
Even under these conditions prolonged loss of sleep is always very 
serious, and after about 10 days the animals have generally reached 
the limit of resistance. During the entire period of this wakefulness 
the need of sleep becomes more and more imperative, and one can 
see among the seeming physiological factors of sleep those which tend 
to increase it and effect the need of sleep and those which do not dis- 
turb sleep and consequently can not be considered as its causes. The 
temperature of the body remains normal, the respiration undergoes 
no variation, and the amount of carbon dioxide in the blood does not 
increase, which enables us to exclude the theories of the impoverish- 
ment of the blood in oxygen and its enrichment in carbon dioxide as 
actual causes of sleep. Neither the blood nor the brain lose their 
portion of water, and this fact combats the theories that explain sleep 
by dehydration. Toward the tenth day the animal can no longer 
keep its eyes open; its paws are continually bending, it has lost all 
sensorial activity and only the strongest kind of stimulation will 
induce reaction. At this moment the brain shows cellular disturb- 
ance, localized exclusively in the frontal lobe, such as could not have 
been brought on by other means, and which, therefore, seem to be 
characteristic of insomnia. If such an animal is left to sleep at will, 
he plunges into a deep sleep from which he awakens completely 
refreshed, normal, and the alterations in the brain have then disap- 
peared. ; 
- Prolonged wakefulness, therefore, is thus shown to bring on an 
imperative need of sleep and some cellular modifications in the frontal 
lobe of the brain. To what are these phenomena due? Is it to 
exhaustion or to intoxication? We are thus brought back to reex- 
amine some of the chemical thoeries for which we sought to find an 
experimental basis. 
