Progress during the year has been notable in each of the major fields of biochemical study: (1) photosynthesis, by which carbon is reintroduced into the biological cycle for both plants and animals; (2) the chemistry of plant growth, in a nutritional sense; (3) the mineral and organic requirements for animal nutrition; (4) basic cellular reactions by which foodstuffs are burned and energy is derived for life processes; and (5) the chemical aspects of fighting diseases.
Plant Chemistry.
Storage of Carbon Dioxide.
In the over-all economy of plants and animals, probably no chemical reaction is of more interest or fundamental importance than that of recovering carbon dioxide from the air and storing it in complex products such as sugars, proteins, fats and their related constituents of living cells. A primary clue of the greatest interest was provided by the use of radioactive carbon at the University of California, where it was found that the apparent first entry of carbon dioxide into a fixed, complex substance in the cell was to form the acidic carboxyl (-COOH) group in an acid of fairly high molecular weight. There is some evidence that one of the primary steps in photosynthesis is a reversal of the reaction by which carbon dioxide is known to be split out of the cellular products of oxidation. Vitamin B1 plays the role of a catalyst for the reaction by which carbon dioxide is formed in both plants and animals, thus linking one of the first-discovered vitamins with both respiration and photosynthesis. Copper, vitamin C and the carotenoid pigments are also highly concentrated with chlorophyll in the granules where photosynthesis takes place. The photosynthetic reactions are extremely sensitive to the effect of inhibitors or poisoning reagents that affect cellular respiration at higher concentrations, thus further linking together the general course of the two major types of reaction in plant cells.
Plant Nutrients and Stimulants: Vitamins.
In their study of mineral requirements for plant growth, Arnon and Stout observed an increased rate of growth when molybdenum salts were supplied to tomato plants in a concentration of 1 part in 100 million, thus adding a new element to the steadily growing list of 'essential' nutrients. Three laboratories obtained further evidence of the essential nature of silicon for plant growth; and additional evidence of the importance of boron for the growth and fruiting of cotton plants was found at the Georgia Agricultural Experiment Station. At Columbia University, extreme variations in different plants were found with respect to calcium and magnesium requirements and antagonisms, and also in relation to the effect of selenium. The latter element is toxic toward many plants, but evidence was obtained of a positive effect upon growth in some plants. Lundegardh observed a marked stimulating effect of manganese salts upon the respiratory activity of wheat root cells, and suggested that in some plants, the role of manganese is similar to the role of iron in others.
The importance of organic nutrients for plant growth has become recognized more clearly, and fascinating insights have been provided to explain many peculiarities of plant behavior — particularly the effects of one kind of plant upon another, and the interrelationships of plants and animals. Many of the phenomena related to symbiosis, parasitism and soil fertility are clearly dependent upon the supplying of vitamin-like compounds, or bioses, from one plant to another or from animals to plants. In the past, the emphasis has generally been in one direction only — plants providing vitamins for animals. The isolated, pure vitamins of the B-complex have been particularly useful in studying plant growth requirements. The growth responses of different lower plant forms (bacteria, yeasts and molds) have been found to be so specific in a number of cases that they provide a basis for quantitatively measuring the vitamin content of foods and extracts from animal tissues. Such quantitative relationships have been demonstrated for thiamine (B1), riboflavine (B2), nicotinic acid amide (G), and the filtrate factor (related to pantothenic acid). Vitamin C also acts as a growth-promoting hormone. One of the most striking relationships of this kind was brought out by Moewus (University of Erlangen), who found that some of the green algae were sensitive, as measured by their capacity for locomotion, to a concentration of 1 part of crocin in 250 trillion parts of nutrient solution. Crocin is a glycoside of crocetin, a fatty acid closely related in structure to vitamin A, phytol, and the carotenoid pigments. Vitamin B1 has come into common usage almost suddenly as a growth stimulant in household flower culture. Cystcine, a common unit in proteins, also came into wider recognition for its growth-promoting activity in plants.
Wound Hormone; Fatty Acids.
The plant wound hormone, traumatic acid, was isolated and identified as 1-decene-1, 10-dicarboxylic acid by English, Bonner and Haagensmit during the year. Injury to plant tissues stimulates formation and activity of the hormone in the processes of cell proliferation and wound-healing. Another development of special interest related to fatty acids in plants was the extension of the chaulmoogric acid series to include four new members, by Cole and Cardoso. The two higher homologues, known earlier, are perhaps the most effective agents available for combatting leprosy.
Animal Nutrition.
Zinc.
The animal requirement for minute amounts of mineral elements has continued to be an active and fruitful field of investigation. No new elements were added to the 'essential' list during the year, but a clearer insight was gained concerning the function of the less common elements. One of the striking discoveries was the finding by Keilin and Mann that a zinc-protein compound could be isolated from beef red blood corpuscles (0.31 to 0.34 per cent Zn). The zinc compound proved to be the catalyst that controls the conversion of carbonic acid to carbon dioxide and water, hence called carbonic anhydrase. Zinc thus controls one of the major respiratory functions in the animal body, making it possible for carbon dioxide to escape from the blood stream as it courses through the lung capillaries.
Copper.
The role of copper in the animal body was further clarified by Schultze, who found that the copper intake constituted a limiting factor in the rat's capacity to make one of the major oxidative catalysts, cytochrome oxidase. The chemical nature of cytochrome oxidase, however, is not fully known; hence the role of copper in this case may be analogous to its role in making possible the synthesis of hemoglobin and other iron compounds.
Cobalt.
Elvehjem and associates have demonstrated the essential role of another metal, cobalt, for hemoglobin synthesis in dogs. Previous observations under natural grazing conditions had correlated cobalt deficiency with anemia in cattle and sheep, but an experimental deficiency had not been accomplished. The new finding makes it possible to study the role of cobalt under carefully controlled laboratory conditions.
Manganese has been further studied by Norris in relation to perosis (slip, or detachment of tendons) in birds. A low intake of the metal in chick diets also resulted in low egg hatchability and high chick mortality.
Selenium.
No evidence has appeared to indicate that selenium has a nutritive value for animals, but additional evidence concerning its toxicity was reported by Twomey and associates, who observed fairly extensive selenium poisoning of ducks under natural feeding conditions.
Fluorides.
Although most of the biochemical studies on fluorides have dealt with their toxicity, evidence now indicates that a marginal intake of fluoride affords a certain degree of protection against dental caries. Cox and associates have succeeded in producing experimental mottled enamel in rats, and have further demonstrated a protective effect against dental caries in rats under carefully controlled experimental conditions. McKay, Dean, and others have observed from clinical survey data a positive correlation between mottled enamel areas and a low incidence of dental caries. Armstrong and Hodge have contributed further observations that indicate a beneficial effect of fluorides upon tooth structure and resistance to caries. The normal presence of fluorides in bones and teeth has been recognized over a long period.
Vitamin B-complex.
Rapid progress has been made in the study of the vitamin B-complex, both in relation to the number of factors that are included in the complex, and in regard to their structure and function. Elvehjem regards the evidence to be satisfactory for the existence of at least 10 separate entities in the 'B-complex.' Of these thiamine (B1), riboflavine (B2), nicotinic acid (G) and B6 have been identified as pure compounds and synthesized on a commercial scale. Beta-alanine is known to be an essential part of the 'filtrate factor' and pantothenic acid (possibly identical). The other factors are essential for either rats or chicks or both. The existence of an anti-gray hair factor has been verified in a number of laboratories, but there has been no evidence that gray hair in people is related to such a nutritional deficiency. All of the above four isolated factors have been shown to be essential for human nutrition, as shown particularly by Spies, Sebrell and associates through their feeding of pure vitamin supplements to pellagrins.
Vitamin K.
Vitamin K has been isolated and synthesized in a number of laboratories, largely through the work of Dam, Almquist, Daisy, Ansbacher, Anderson, Fieser and associates. A whole series of 2, 3-substituted anthraquinones, natural and purely synthetic, can serve as vitamin K in the body. Clinical usage of vitamin K (both natural and synthetic) to promote blood clotting has been very widely adopted. Aside from the early discovery of the existence of the vitamin by Dam, nearly all of the later progress was accomplished in American laboratories.
Vitamin C.
Studies of the functional role of vitamin C have led to confirming its close relation to tooth development, resistance against bacterial toxins, and to complement activity in the blood stream. The rate of synthesis in rats was brought under experimental control to a great extent by the work of Longenecker and associates, using pure compounds to effect an increased rate of synthesis and excretion. The vitamin is also an important factor in regulating the metabolism of aromatic amino acids, as shown by Levine and associates. Peugnet observed a functional rôle, in association with copper, in regulating the heart (frog).
Nutrition and Teeth.
The predominant importance of good nutrition for the development of sound teeth and protection against the incidence of dental caries was brought out in striking fashion by extensive surveys in England, particularly those reported by Read and Miller and their associates. According to their findings dental hygiene, as ordinarily understood, has little to do with protection against tooth decay, at least up to the age of 14 years.
Physiological and Clinical Chemistry.
The success of Cori and associates in demonstrating the synthesis of glycogen from hexosephosphate in vitro, by means of an enzyme extracted from muscle, was a finding of great fundamental significance. A key was thus provided to one of the most important physiological reactions — the synthesis and hydrolysis of muscle glycogen, on which most of the mechanical and chemical energy of the body depends.
Micro-methods of blood and tissue analysis, as extended during the year by Borsook and associates and others, opened up valuable techniques for the study of tissue changes. Fairly comprehensive analyses for intermediate metabolites can thus be made with samples as small as 0.1 to 0.2 ml. of blood. Of similar widespread importance are the rapidly developing micro methods for vitamin and mineral analysis, by which the state of nutrition of a person or animal can be determined with a degree of certainty that greatly enhances the possibility of detecting border-land types of malnutrition — a field of diagnosis that should greatly advance public health work.
The use of stable and radioactive isotopic elements in biological 'tracer' work has been adopted with great rapidity. Radioactive iron, phosphorus, sulfur, sodium and potassium have been used very widely, and the use of heavy hydrogen (deuterium), heavy nitrogen and heavy carbon has been extended steadily.
Considerable success has been achieved in the separation of compounds from kidney tissue that can be used for the study and perhaps the control of high blood pressure.
The preparation and use of sulfapyridine-type compounds for combatting infections has continued rapidly, with increasing effectiveness in clinical practice. Sulfathiazole has been especially promising as a new product. Approximately 800 such compounds have already been studied.
Enzymes and Respiratory Carriers.
The problem of isolating and identifying enzymes and respiratory catalysts has been studied extensively and with continued success. Papain, a protein-splitting enzyme was isolated from plant sources by Balls and Linneweaver. Chymotrypsin, a protein-digesting enzyme isolated earlier by Northrup and associates from the pancreas was converted into two new crystalline enzymes by Kunitz. The latter also isolated a ribonuclease from beef pancreas. Sumner, who was the first investigator to isolate successfully a crystalline enzyme (urease), recently succeeded in isolating another important enzyme, catalase.
The respiratory-carrier enzymes studied most effectively during the year have been those containing riboflavins linked to specific proteins, active carriers in the first steps of burning foodstuffs within the cells. Considerable progress was also made in identifying cytochrome oxidase and the cytochromes — agents that act most directly upon molecular oxygen as it enters into the chain of reactions that ultimately result in the formation of water and carbon dioxide, plus the energy for life processes. See HORTICULTURE.
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