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An animal can only achieve its full genetic potential if it has lived its life in an ideal environ­ment. Few environments are ideal; they may be unfavourable for numerous reasons and for different lengths of time. Indeed, variations on these themes are almost infinitely possible, but concrete examples will be selected and their effects on the lives of animals and of man demonstrated. Time comes into all this, but its importance and the difference between chronological and biological time have not been properly appreciated. The interactions of time and the environment on the growth of animals and of their organs are complex, but recent work on malnutrition and growth has given us some insight into the matter. Theories that have been formulated are discussed, but none of those yet put forward explain all the facts that can be demonstrated experimentally, and studies that might provide clues have been neglected.

The behaviour and nervous activity of rats which had been made to grow fast by a super-abundance of food in the first week or two of life were compared with the same characteristics in litter-mates which had been suckled in large litters, and gained weight much more slowly. The rapidly growing animals were more active and inquisitive at each chronological age than their slow-growing litter-mates, and they appeared to profit more by previous experience, which indicates that they learned more quickly. It is suggested that nutritional variables may underlie some of the correlations which have been found by others to exist between physical and mental development at similar chronological ages in children. It is also possible that children today, who are admittedly growing faster than they did 50 years ago, should be expected to display a correspondingly greater mental activity and ability to learn.

In continuation of the work of Widdowson & McCance (1960), previously published in the Proceedings , groups of rats growing rapidly after a high plane of nutrition during suckling were undernourished for 3 weeks so that their weights at 6, 9 and 12 weeks of age were the same as those of rats which had been growing slowly after a lower plane of nutrition during the first 3 weeks of post-natal life. The undernourished rats were then rehabilitated by being given unlimited food. Undernutrition after weaning made progressively less difference to the ability of the rats to make a complete recovery, so that, whereas a low plane of nutrition during suckling produced smaller animals at maturity, and so to a lesser extent did a low plane of nutrition from 3 to 6 weeks, undernutrition from 6 to 9 weeks did not do so. Undernutrition from 3 to 9 weeks, however, did prevent the animals attaining the same size as the controls. Although their weights might be the same at death the size and composition of rats which had grown fast and then been undernourished differed in characteristic ways from those which had grown slowly and steadily all the time. The bones were longer, the testes and stomachs were heavier, the livers, spleens, skins and small intestines were lighter. The chemical findings were in keeping with the anatomical ones.

The total amount of DNA and the protein/DNA ratio have been measured in the kidneys, heart, liver, and gastrocnemius muscles of 56 human fetuses and newborn infants of 13-42 weeks' gestational age. The total amount of DNA in each organ approximately doubled every week up to the 25th; thereafter the rate of increase was slower. The protein/DNA ratio in each organ increased rapidly in the last 10 weeks of intrauterine life. Before 30 weeks there was some increase in the protein/DNA ratio in the kidneys, heart, and gastrocnemius muscles, but no significant change in the liver. In 5 small-for-dates infants the protein/DNA ratio was normal, whereas the total DNA tended to be low.

Specimens of urine were obtained during the forenoon from 45 Ugandan and 45 British boys and girls below 4 years of age who were attending clinics for healthy children. By employing known facts about the excretion of creatinine, and by making certain assumptions, it was possible to obtain a surprising amount of information about the nature of the food consumed. This agreed well with what was already known about it. The method has distinct possibilities and could be made more quantitative by using a reference group about which more was known.

Summary 1. Sodium chloride was added to the milk given to premature infants and newborn piglets which were then reared by hand. 2. The addition of salt led to (a) an abnormal increase of weight; (b) a rise in the serum sodium and chloride; (c) an expansion of the extracellular volume and ultimately massive oedema; (d) a reduction in the catabolism of tissue protein; (e) no increased excretion of potassium, if anything the reverse. 3. Similar and. even more clear cut results were obtained when the piglets were given water and salted water instead of milk and salted milk. 4. When the administration of salt was stopped the infants rapidly regained their healthy status. Expansion hypertonique des liquides extracellulaires. Du chlorure de sodium a ete ajoute au lait destinea des enfants nes avant terme ainsi qu' a des porcelets nouveaunes qui furent alors eleves au biberon. L'addition de chlorure de sodium au lait amena: a) une augmentation anormale du poids oorporel, b) une augmentation du taux du sodium et des ions chlores dans le serum, c) une augmentation du volume des liquides extracellulaires et subsidiairement un œdeme massif, d) une reduction du catabolisme des proteines tissulaires, e) une diminution plutot qu'une augmentation de l'elimination du potassium. Des resultats analogues et meme plus nets encore ont ete obtenus chez des porcelets nourris d'eau et d'eau salee au lieu de lait et de lait sale. Une fois que le sel eut ete supprime, les bebes redevinrent rapidement bien portants. Hypertonische Ausdehnung der intracellularen Flussigkeiten. Kochsalz wurde zur Milch zugesetzt, die fruhgeborenen Sauglingen und neugeborenen Schweinchen verabreicht wurde. Der Salzzusatz bewirkte: a. eine abnormale Gewichtszunahme, b. eine Steigerung im Natrium-und Chloridgehalt im Serum, c. eine Expansion des aussercellularen Volumens und schliesslich massives Oedem, d. eine Reduzierung im Abbau der Gewebsproteine, e. keine Erhohung, wenn nicht Herabsetzung der Kaliumausscheidung. Ahnliche und sogar eindeutigere Resultate wurden erzielt, wenn die Schweinchen Wasser und Salzwasser anstatt der Milch und der gesalzenen Milch erhielten. Wenn die Verabreichung des Kochsalzes unterbrochen wurde, kehrten die Sauglinge rasch zu ihrem gesunden Zustand zuruck. Expansion hipertonica de los liquidos extracelulares. Se anadio cloruro de sodio a la leche suministrada a prematuros y tambien a lechoncillos recien nacidos criados a mano. La adicion de la sal condujo a: (a) aumentacion anormal de peso, (b) ascenso del sodio y cloruro sericos, (c) expanson del volumen extracelular y finalmente edematizacion masiva, (d) reduccion catabolica proteicotisular, (e) aumento nulo de excrecion potasica y mas bien lo contrario. Resultados analogos y todavia inas pronunciados obtenidos cuando se suministro a los lechoncillos agua y agua salada en lugar de leohe y leche salada. Al suspenderse la administracion de sal, los ninitos recobraron rapidamente las condiciones de la salud.

Three classes of highly inbred 16-week-old mice, of strain A 2 G / Tb , were studied: (i) controls, kept at 21 °C; (ii) ‘new stock’, of the first or second generations reared in a room kept at –3 °C; (iii) ‘old stock’, of the fourteenth generation reared at –3 °C. All were bred at the same time. The new - stock mice were lighter than the controls, their tails were shorter, and they (especially the females) had less fat. They contained more water, and less nitrogen and collagen. The males, but not the females, had less calcium and phosphorus. The heart, stomach and small intestine were heavier than in the controls, and the intestine was longer. Liver and kidneys, too, were heavier, but these differences were large only in the females. The shaved skin was lighter, but the hair, especially in the females, heavier. Gonad weights were lower. The spleen tended to be lighter, but varied greatly. Most of these differences from the controls resemble those seen in adult laboratory rats exposed to cold for a few weeks. The old stock , of both sexes, had almost the same body-weight as the controls, but re­sembled the new stock in tail-length: hence the effect of cold on growth of the tail was inde­pendent of body-weight. The old-stock males had more fat than the controls, while the females were intermediate between the controls and the new stock. The males contained less water than the controls; while in nitrogen, collagen, calcium and phosphorus they did not differ significantly. The tendency to return towards the control state was less marked in the females. In weights of stomach, intestine and liver the old-stock males again resembled the controls; and their kidneys were lighter . They had, however, longer intestines than the controls and, like the new stock, they had heavier hearts. Their skin was lighter but hair, heavier. The spleen was lighter. Except in their kidneys and spleen, the old-stock females resembled the new-stock females, rather than the controls. Since other work has shown that the old-stock females are more efficient mothers than the new-stock, the old-stock mice of both sexes were clearly better adapted to cold than the new. This may have been due to intracellular changes making individual tissues more efficient. The change in the old stock cannot be due to selection of favourable genotypes; it may be due to a cumulative maternal effect.

An experimental automatic electrode system was constructed to determine the feasibility of making routine determinations of blood pH, pO2, pCO2, sodium, and potassium in intensive care units. The equipment standardizes itself automatically every 25 min, and is self-cleaning after a blood specimen has been analyzed. The analyzer is connected on-line to an IBM 1800 computer on an interrupt basis. There was no significant difference between the results for pH, pO2, and pCO2 obtained with this machine and those by manual methods. The precision obtainable for the five determinations is given. The relationship between blood and plasma sodium and potassium activities determined with the glass electrodes and plasma sodium and potassium concentrations determined by flame photometry is discussed.

1. Rats 10 weeks old were fed for 9 weeks either on a stock diet containing 17% protein, or on a low-protein diet prepared from the stock diet with added glucose, minerals and vitamins. Half the animals on each diet were kept at room temperature (21°) and half in a cold environment (5°).2. The calorie intake of the animals kept at 5° on both diets was 60–70% higher than that of the corresponding group at 21°. The animals on the stock diet and kept at 5° gained weight but not so much as those on the same diet at 21°. The animals kept on the low-protein diet at 21° lost weight, while those on the same diet at 5° lost only a little weight initially and none thereafter.3. On both types of diet the liver, kidneys and gastro-intestinal tract weighed more per 100 g body-weight in animals kept in the colder of the two environments; the small intestine was conspicuous in this respect.4. The weight of the fur was greater, and the weight of the skin less per 100 g body-weight at 5° than at 21°.5. The animals on the stock diet at 21° had most fat in their bodies, both in absolute terms and per 100 g body-weight. There were no significant differences between the other three groups.6. The skin of the animals kept at 5° had a significantly higher collagen to N ratio than the skin of those having the same diet at 21°.

The biochemist and the anthropologist look at native food problems from very different points of view, but it seems clear that research on African diets will be of scientific value only if there is co-operation between the two. Without chemical analysis it is impossible to know the composition of any particular native diet. Without a knowledge of the customs and language of any tribal area the necessary facts cannot be collected. The present article describes an attempt at co-operation along these lines, based on a study of the diet of a Northern Rhodesian tribe.

Long before the present century there was general appreciation of the fact that good growth called for good food and plenty of it. Hopkins’s isolation of tryptophane and his pre-occupation with vitamins always led him to emphasize that something more was required and that satisfactory growth was only possible on a ‘balanced’ diet. By this he meant adequate in all respects—proteins in general, amino-acids in particular, calories, vitamins and minerals (Hopkins 1920, 1925). Since that time everything has gone to vindicate Hopkins’s foresight, but a great many further discoveries have been made about the bearing of nutrition on growth. These have all emphasized the co-ordinated nature of the process, and it is with some of these discoveries that this paper will be concerned. The nutrition of children in this country has been progressively altered in the last 40 years by the provision of cheap milk, school meals and a rising standard of living. At each chronological age, moreover, down to the age of 5, the heights and weights of children have been shown to have risen progressively in a number of countries over the last 50 years and to be still rising (Tanner 1955; Acheson i960). The height of adults has probably risen too (Boyne & Leitch 1954; Boyne i960). With this increase in children’s size has gone earlier maturity and all that this involves. These observations on man recall those which Osborne & Mendel (1926) reported from their rat colony over a period of 15 years. The charges described by them were certainly nutritional in origin and considered to be beneficial in every way. McCay, Maynard, Sperling & Barnes (1939) and others, however (Ross 1959; Berg & Simms 1960), have shown in growing rats that prolonged undernutrition and delayed development after weaning may greatly increase the normal life span, and the subject was reviewed by Silberberg & Silberberg (1955) and Comfort (i960). McCance (1953) suggested that the rehabilitation of undernourished German children after the war might be shortening their expectation of life, and it has even been proposed that a progressive curtailment in the expectation of life may be accompanying the secular trends in children’s heights and weights (Sinclair 1955). It is by no means certain, however, that the secular trends are wholly nutritional in origin. They may be due to out-breeding (Tanner 1955) or to other causes (Editorial 1961).

The development of the skeletons of rats reared as described in the preceding paper has been studied in three ways, the appearance of the ossification centres and their maturation, the skeletal proportions, and the chemical composition of the femur and parietal bones. Animals which had grown more rapidly than the average had skeletons which were in all respects more mature at each age than those of animals which had grown more slowly. The skeleton, however, did not mature quite fast enough to keep pace with the rapid growth in weight, so that rapidly growing animals of the same body weight as their slow growing litter-mates, but younger in age, had femora which were shorter and contained less calcium, and their epiphy-seal development was not so far advanced. The chemical development of the femur was appropriate to the length of the bone.

Urine has been collected from infants at the moment of birth and compared in composition with the first urine formed after birth, and with the maternal urine. Cord serum and maternal serum have also been analyzed. Cord serum differs from maternal serum in that it contains a higher concentration of P and frequently also of K. Foetal urine differs from maternal urine formed at the same time, and from the urine formed by an infant immediately after birth in that: ( a ) It usually has a very low osmolar concentration (average 137 mosmol. /l.). The fraction of the osmolar concentration due to NaCl is large and of that due to urea correspondingly small. ( b ) It usually contains slightly more Na than Cl. ( c ) It contains little K and only the merest traces of inorganic P. It follows that sodium chloride in excess of requirement must continually be entering the foetus and that free water must also in some way be made available. The character of the urines can be explained if the kidney before birth is outside the control of the anti-diuretic hormone, the parathyroid hormone, and possibly the suprarenal hormone.

An investigation has been made of the iron intake of sixty-three men and sixty-three women of the English middle class, living on freely chosen diets. Their intakes of total iron have been found to have mean values of 16·8 and 11·4 mg. per day respectively. The highest value found for any woman was only just above the average for the men, and 30 per cent, of the women were taking less than 10 mg. of iron a day.“Available” or inorganic iron in the diets has also been calculated, and has been found to average 10·8 mg. per day for men and 7·9 mg. for women. If fairly large amounts of meat are eaten, the available iron may be less than half the total iron in the diet. If, on the other hand, the diet is mainly vegetarian, about 90 per cent, of the total iron may be available.Haemoglobin determinations were made on more than 50 per cent, of the subjects. The men's average was 102 per cent, and the women's 93 per cent. No significant correlation could be found between the total or available iron intake and the haemoglobin level.The effect of large doses of iron (100 mg. of iron a day as ferrous sulphate or ferric ammonium citrate) on normal haemoglobin levels has been investigated. This has scarcely altered the haemoglobin percentages of men, but has increased the values for women by 4–17 per cent, and a mean rise of over 10 per cent, has been observed.