An analysis of the factors affecting metabolism shows that the influence of food and muscular work is always in the same direction, t. e., to increase metabolism. Are there any conditions in which metabolism can be depressed? In other words, is the basal metabolism capable of any material alteration? Are there variations in it? If so, how wide, and can conditions be imposed upon the body so as to lower the basal metabolism? It is very clear to students of metabolism at the present time that one of the greatest factors in metabolism is the stimulus to cellular activity which is continually acting upon the body-cells. Can the stimulus be lowered? It has been shown by giving a carbohydrate-free diet, thereby developing an acidosis, that the acids do stimulate the cells to greater activity, with a resulting greater metabolism. Is it possible to reverse this condition? The normal existing stimulus consists of acids, chiefly amino, flowing through the blood-stream. It is conceivable that by reducing these amino acids, providing the theory of acid stimulus is true, the basal metabolism may be markedly lowered.

In the subsequent discussion special emphasis will be laid upon those features of the research that contribute to the question of the factors relating to cellular stimulus, most marked among them being the withdrawal from the body of rather large amounts of nitrogen, as indicated by the pronounced negative nitrogen balances found with all of the subjects.

It is indeed surprising that after 15 years' search for a nutritional level with man markedly different from that of the normal individual, such a level should not have been found in all the researches conducted by this and other laboratories. With animals other than man, changes in the nutritional level are by no means uncommon in nature. One has but to think of the long period of hibernation of such mammals as bears, during which the metabolism is sustained, although at a very much lower level than normal. With marmots it has been shown that the body temperature is also much lower than normal. In other words, during hibernation we have animals approaching the cold-blooded stage. Prior to hibernation there is a large accumulation of fat; during hibernation there are, of course, drafts upon body-material to sustain life, even at the lower metabolic level. It is furthermore worthy of note that with bears, at least, the birth of young occurs during hibernation.1 It would seem to be a provision of nature that these animals born during hibernation have an extraordinarily small birth-weight. Instances are not uncommon of bears weighing over 500 kg. having young with a birth-weight of 500 grams. Furthermore, after birth there is a relatively long period of suckling, in which the bear cub subsists wholly upon its mother's milk, this period occurring entirely during hibernation. This small birth-weight in proportion to adult weight - a proportion that we believe exists nowhere else among mammals - is unquestionably a minimizing of drafts upon body-material during hibernation.

1 Personal communication from Dr. C. Hart Merriam, Washington, D. C.

With other animals and, indeed, with fishes, pronounced changes in nutritional level are frequently observed, particularly prior to the breeding season. Thus Parker1 specially emphasizes the prime condition of the bull seals in the Pribilof Islands at the beginning of the mating-season. Throughout this time, according to Parker, no food is taken and the physical combats Of the mature animals in the various rookeries are very fierce; at the end of the breeding-season the bulls are distinctly in a depleted muscular condition.

"The bulls, as a result of their incessant activities, are in a state of extreme emaciation. Many of them have been on the beaches from May, and during the period between the time of their arrival and the end of July or early part of August, they touch no food. This fast of well over two months, coupled with their incessant activity, drains them of all their stored energy. Their fat disappears and they are reduced almost to skin and bones. In this state they may be driven off a rookery without resistance and they soon return to the sea to begin the winter migration. During this period they feed and fatten in preparation for the coming season".

Miescher's notable observations2 on the migration of the salmon in the Rhine and the severe drafts upon muscular tissue primarily made for transformation into testicular or ovarian tissue are all called to mind as provisions of nature for marked transitions in nutritional level. Thus, Miescher shows that the salmon, after coming to the Rhine from the sea, virtually starve. Yet the generative organs of both male and female develop greatly, this being at the expense of the muscles, which may lose 55 per cent of their weight. Even after 5 to 15 months' fast in fresh water, during which time they lay their eggs, Miescher found fat globules in the muscle-cells of salmon.

In addition to the classical work of Miescher, to whom we have been indebted for practically all of our knowledge on the composition of the migrating salmon, it is a great pleasure now to be able to cite two especially fine pieces of American research, that by Greene3 and more recently that by E. D. Clark and L. H. Almy,4 who fully confirm and extend Miescher's observations.

In view of this adjustment to conditions, it is somewhat surprising that the popular conception of emaciation and nutritional level should be so antagonistic to any reduction in body-weight. In reality, there is no biological reason why there should not be at least a periodic change of considerable degree in the nutritional level with man. Since these changes in the nutritional level may have profound significance in reproduction, judging from the lower animals, it thus becomes important in making as comprehensive a study as practicable of the welfare and general physical condition of man to include observations of possible influence upon reproductive processes.1

1 Parker. Scientific Monthly. May. 1917, p. 393.

2 Miescher-Reuach. F., Statiatiache und biologische Beit rage zur Kenntniss vom Leben des Rbeinlachaea im Suaawasser. Internat. Fischerei-Auastellung, in Berlin. 1880. p. 154; see also Mieaeher-Reuaoh, Die histochemischen und physiologischen Arbeiten, Leipsic, 1887. p. 118. Cited by Clark and Almy, Journ. Biol. Chem., 1918, 33, p. 497.

3Greene, Journ. Biol. Chem., 1912. 11, p. xviii; see also same journal, 1918, 33, p. xiii.

4Clark and Almy, Journ. Biol. Chem., 1918. S3, p. 483.

Nature has thus provided for material changes in the nutritional level, and particularly for possibilities of long drafts upon body-material either with deficient nutrition or during complete fasting. But there is likewise (among animals, at least) a pronounced rise in weight on the return to normal feeding after the prolonged drafts. For instance, immediately after hibernation, the bears begin to eat voraciously and accumulate a storage of fat preliminary to the next season's hibernation. The seals proceed to their feeding-grounds and return the following year in prime condition. This recovery of weight after hibernation or after low nutritional level must be considered likewise in this study with men. Fortunately, our observations throw some light upon the rapidity of return to body-weight after a prolonged period of reduced diet and contribute materially to this question.

It would appear that with humans those individuals who are accustomed to frequent or relatively frequent fasting have a distinct tendency to increase in weight. The excessive eating following restricted diet has been noted in a great many places. One of us, on a visit to Petrograd, was informed by Professor Pawlow that the sale of the artificial gastric juice prepared in the Laboratory of Experimental Medicine was relied upon in large part to sustain the experimental laboratory. Prior to the war, Russian fast days were very frequent, and Professor Pawlow remarked that if one plotted the Russian fast days and also the sale of artificial gastric juice, it could be seen that peaks in the curve of the sale of gastric juice invariably followed a few days after each fast day. In other words, after fasting the Russians ate voraciously; this produced digestive disturbance and they would then purchase the gastric juice for therapeutic purposes. Our own experience with a number of the subjects of the low-diet research bears out in general these experiences, i. e., that following a period of restricted diet there is a distinct tendency toward overeating and like-wise toward a rapid and frequently a sustained increase in body-weight.

The experiences of athletes likewise tend to show that after a period of athletic training with restriction in diet and severe muscular exercise there is a proneness to take on considerable weight. Nevertheless these conditions have been so commonly overlooked by physiologists that, so far as we are aware, no specific studies of metabolism have been made for these apparent variations in nutritional level with man, or such simple indices of metabolism as pulse-rate and blood pressure recorded under these conditions. In the following chapters we purpose discussing the effects of a prolonged reduced diet and its accompanying state of nutrition upon the various physiological and psycho-physiological processes of a group of men.

1 See page 638; also Miles, Journ. Nervous and Mental Disease, 1919, 49, p. 208.

To tabulate the results of this research and prepare the material for publication would have been an impossibility without the intense cooperation of Miss Annie N. Darling, to whom the editorial revision of the entire manuscript has fallen; of Mr. William H. Leslie, who, as chief of the computing division of this Laboratory, has untiringly labored to secure both rapid and accurate tabulation of the results; and of Miss Elsie A. Wilson, who has unremittingly labored on much of the abstracting, as well as the computing and tabulating. Our obligation and gratitude to these cooperators is extreme. Mr. Leslie was ably assisted by the Misses Frances E. Kallen, Anna M. Burns, Marion L. Baker, Mary D. Finn, Mildred J. L. Manning, and Helen C. Waldron. The drawings used in this report were for the most part the result of the skilful attention of Messrs. Edward L. Fox and Alden K. Dawson.