In relation to biochemistry, the two fields in which most rapid progress was made during the year 1940 were (a) in the use of radioactive 'tracer' elements and (b) in the study of vitamins. Each of these two types of study was extended into many phases of the broader problem of gaining a better understanding of the chemical reactions that characterize living cells.
Biochemistry.
Animal Cell Utilization of Carbon Dioxide.
One of the most far reaching discoveries of the year was the finding (corroborated in different laboratories) that animal cells can maintain a rigid utilization of carbon dioxide gas, building it into their tissue constituents such as glycogen (animal starch) and certain organic acids. It has long been known that green plants can utilize carbon dioxide during photosynthesis to form starch, sugars, and other cellular ingredients. In animal cells, however, carbon dioxide has been looked upon as an end product, without thought of its re-use in cellular synthesis. The new evidence was obtained by the use of short-lived radioactive carbon, so that the experiments were of necessity very limited in time range. When larger quantities of the more suitable form of radioactive carbon (longer half-life) become available, investigations of a biochemical nature will be facilitated to an unprecedented degree.
Source of Energy for Photosynthesis.
The energy required for photosynthesis in green plants must come ultimately from sunlight, but during the past year two discoveries extended the recognition of relatively new factors that may be involved. Chlorella cells (a green, microscopic, unicellular plant) were found to continue reactions that constitute a part of the over-all photosynthesis through unexpected long periods of darkness. Under special circumstances, too, the cells could utilize hydrogen gas as a significant source of energy.
Formation of Animal and Plant Starch.
Cori's brilliant demonstration that glucose (blood sugar) forms an intermediate phosphate ester, glucose-1-phosphate, from which animal starch (glycogen) is formed directly in muscle and liver cells, has been extended in a general way to include the formation of starch in plants.
Plant Immunity.
An interesting phase of research relative to immunity was opened up by the finding that certain green plants and moulds could acquire immunity against different kinds of infectious (and virus) diseases, analogous to the long-recognized development of immunity against disease in animals.
Use of Radioactive 'Tracer' Elements.
The radioactive minerals, such as potassium, sodium and phosphate salts, have been used with notable success in following the course of salts through different channels of circulation in plants, and also in the basic study of cell permeability.
Copper.
Radioactive copper was found to be distributed rapidly into the tissues of anemic albino rats. There copper gave rise to the formation of active respiratory catalysts containing iron. Two of the major respiratory enzymes, cytochrone oxidase and catalase, are thus dependent upon the availability of copper as well as iron in such tissues as the bone marrow and liver; within 24 hours very low levels of activity are raised practically to normal by the feeding of minute amounts of copper.
Fluoride.
Increasing attention centered on the apparent function of fluoride as a factor of significance in relation to the development of good teeth. High fluoride intakes clearly produce mottled enamel, but there has been increasing evidence that intermediate levels may aid in the prevention of dental caries.
Vitamins.
The chemistry of the vitamins progressed rapidly along four major lines, (a) identification of new vitamins, (b) working out quantitative methods of chemical analysis that can be applied to tissue studies, (c) finding the chemical reactions by means of which the vitamins function in living cells, and (d) studying the significance of the vitamins in relation to human health.
Identification of New Vitamins.
Water-soluble forms of vitamin K were introduced widely, making the administration of the product simpler and obviating the parallel use of bile salts. Pantothenic acid, recognized first as a yeast stimulant by R. J. Williams, was found to be identical with the chicken anti-dermatitis factor and also to be one of the factors in the old vitamin B-complex that is essential for rats. Direct synthesis proved its constitution beyond doubt and provided an abundance of the pure compound for plant, animal, and clinical research.
Of similar interest was the finding by Wolley that inositol, recognized for many years as a yeast growth stimulant, or bios, was an essential factor in the nutrition of white mice. Apparently this new member of the vitamin family is not essential for rats, though very widespread in occurrence.
The anti-gray hair factor, required by rats and foxes, and once thought to be a single vitamin, was shown to be a multiple factor; at least some of the types of graying can be cured by riboflavin, vitamin B6 or even certain minerals.
Commercial Production.
Among the outstanding accomplishments of the year was the production of pure riboflavin in commercial quantities at low cost by plant growth. The commercial production of vitamin B1 and nicotinic acid by chemical synthesis has advanced rapidly to meet an expanding market. The low-cost availability of these three dominant members of the vitamin B-complex has added a great impetus to the movement to restore the vitamin content of wheat flour, so that a highly satisfactory grade of flour will be available with a content of the above three vitamins that is equal to that of whole wheat. Government officials, nutrition workers, the medical profession and the industrial millers have cooperated in making such a product available because of its evident contribution to public health. Realization of the extent of malnutrition in the United States and an intense effort to focus attention upon factors that would contribute to improved national health and efficiency have added force to the long over-due emphasis upon a bread of high nutritional quality.
Study of High Blood Pressure.
Very encouraging progress was made in the chemical study of substances that cause or alleviate high blood pressure. Proteins formed in the kidney tissue and circulating in the blood stream appear to comprise the primary disturbing factors. Restriction of the blood supply to the kidney, as shown earlier by Goldblatt, can cause the experimental type of high blood pressure, and evidence has accumulated rapidly to show the importance of the experimental animal technique in an approach to the clinical problem.
Chemotherapy.
The phenomenal success of synthetic sulfanilamide and sulfapyridine type compounds in the treatment of pneumonia and other diseases has led to very extensive studies of molecular structures that might provide even more effective agents in medical practice. Sulfathiazole (2-sulfanilylaminothiazole) was approved for general use by the medical profession. It was found to be especially effective in treating pneumococcic and staphylococcic infections and had less tendency to cause nausea. Two additional compounds of related structure appeared to be very promising: sulfadiazine (2-sulfanilamidopryimidine) and sulfaguanidine (sulfanilylguanidine). Because of its very low rate of absorption from the intestinal tract, the latter compound was viewed as especially promising for treatment of infections in the intestinal tract. The progress that has been made has been largely on an empirical basis, following analogies in structure rather than principles of a physiological nature. The results with the new tools of research, however, have greatly stimulated a renewal of interest in fundamental research in the field of chemotherapy. See also CHEMISTRY.
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