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INDUSTRIAL AND ENGINEERING
before. In short, your work teaches the individual how he may ascend, without legislative, political, or religious forces, to a higher plane of life and thus lead a happier and nobler existence. I n accepting the medal, Dr. Sherman stated that the chief credit for the research recognized by this award is due to Columbia and to the changing company of young chemists who worked with him there: While the award is technically for work published during the past three years, it is also true that this rests upon other work
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extending a dozen years further back. At different times during these fifteen years I have been fortunate in having about forty co-workers in vitamin research to whom I here make grateful acknowledgment as having been each a full partner in some phase of the work. And if any of us has succeeded in seeing a bit beyond the previously known in any direction, it is because we have stood on such giant shoulders as those of our present guest from New Haven [Professor Mendel], and of other American, British, Dutch, and Scandinavian investigators who had entered the field of vitamin research before us.
Chemistry of the Vitamins With Special Reference t o Quantitative Aspects H. C. SHERMAN, Columbia University, New York, N. Y. date is vitamin C. Lynd in 1757 attributed antiscorbutic activity to “something become known through its nutritional contained in the natural juices,” and Budd, activity. I n this respect the case is in 1841, definitely discussed the antiscorparallel to that of enzymes, of hormones, and butic substance as a tangible, chemical eleof the radioactive elements which also bement or compound, “which,” he said, “it is come known by their activities. hardly too sanguine to state, will be disAs in the first isolation of radium, so in the covered by organic chemistry or the experiisolation of a n enzyme or of a vitamin, progments of physiologists in the not far disress is best guided and judged by quantitatant future.” The prediction was sound; tive measurement of the characteristic acbut its fulfilment had to wait until chemist i v i t y a t each important step. And this is try and physiology came closer together. but one aspect of the general situation in Seventy-odd years later, chemistry had suffiwhich we find ourselves by virtue of the fact ciently broadened its views and methods on that the chemistry of today seeks consistently the physiological side to include the systemto develop itself into an ever more and more atic use of laboratory animals as reagents and exact science. I n chemistry, therefore, the word “quaninstruments of research. Holst and Frolich H. C . SIXERMAN a t Oslo, Hess in New York, and Cohen and titative” implies not an emphasis upon quantity as against quality, but rather upon exactness, pre- Mendel a t New Haven, had shown the possibility of making cision, and refinement of knowledge-and this in the inter- the guinea pig a reagent for the study of the antiscorbutic est both of its abstract advancement and of its concrete ap- substance; and La Mer, Campbell, and I, simultaneously with workers at the Lister Institute, developed the quantiplication. Thus, the development of quantitative methods for the tative aspect of such testing and used it in studies of the measurement of vitamin values contributes both to guide behavior of vitamin C under systematically varied condithe isolation of these substances and, simultaneously as well tions. The properties thus revealed led, especially through as subsequently, t o study their behavior with the double the work of Kohman and Eddy, to the guidance of technical objective of learning how to conserve vitamin values and processes for the conservation of this vitamin in foods; and what the behavior of a given vitamin indicates its chemical guided also the laboratory concentration of the substance and its final isolation and identification as a hexuronic acid nature to be. Quantitative methods also enable us to obtain more exact by King and co-workers. Among the alternative structures knowledge, and therefore clearer and deeper insights, as to still possible under this identification, that suggested by the distributicn of each vitamin in nature and its natural Euler seems most closely in accord with the experimentally chemical, genetic, and nutritional relationships and sig- established properties of the substance. nificances. VITAMINA Hence many lines of what in itself would appear to be The quantitative measurement of vitamin A values was qualitative knowledge are found to be best developed by quantitative methods. a t first greatly handicapped by differences in behavior of The time assigned for the present talk permits of only experimental animals. This was found to be chiefly due sketchy mention of a few samples of the work which has ad- to the fact that the body can store this vitamin in large vanced our knowledge of the chemistry of the vitamins %mounts when opportunity offers. The presence in the through the study of its quantitative aspects. These samples body of variable stores of vitamin A is a matter of even will be taken, necessarily in fragmentary fashion, from among greater significance than has yet been adequately recognized the many studies which have been made upon vitamins C, A, and this is doubtless an important reason for the apparent and G, respectively. confusion of evidence and resulting divergencies of opinion (Each of the following three sections was amplified by ex- as to the importance of vitamin A in human nutrition. For hibition and discussion of lantern slides.) purposes of quantitative feeding experiments, the test animals are now first depleted of their surplus bodily stores of VITAMIN C vitamin A, after which their body-weight responses serve as Of the substances now called vitamins, the one which measures of the vitamin A values of the materials fed. (This appears to have been clearly apprehended a t the earliest work thus finds a means of utilizing the advances previously
T
HE existence of each vitamin has first
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made by Osborne and Mendel in the use of growth rates of laboratory animals in their studies of the proteins.) Quantitative correlations then became possible, and finally the fact that carotene is precursor to vitamin A was established. But until after much further research we can feel no justifiable assurance that the carotenes are the only precursors or that all precursors have been discovered and evaluated. Feeding methods must therefore remain our chief or ultimate reliance in this field of investigation for a long time to come; but the feeding methods hitherto available have required continuous (or frequently replenished) supplies of each material under investigation, for a matter of weeks. Many of the re5earches needed for the working out of the relation of the vitamin to its precursors, their development in plants, their stability in storage, and the role of the vitamin in the animal body can be greatly advanced by the use of a method of evaluation by single feedings, such as Dr. Todhunter has developed in her work in our laboratory. VITAMING Vitamin G (Bz) values can be quantitatively determined by means of the general method developed through the experiments of Dr. Bourquin in our laboratory. In these experiments any nutritional essentials not definitely known were doubtless supplied, partly through the food which supplied the vitamin G and partly through the body stores of the experimental animals. When fractionated materials were fed (experiments of Halliday) or when animals of a different nutritional background were used (experiments of Alleman) indications of the participation of a “new” factor appeared. The significant role of body storage of such a factor was suggested anew by the experiments of Carlsson; Stiebeling’s fractionation experiments also indicate that the “nutritional factor” which is called vitamin Bz or G may be a multiple factor containing at least two substances. Thus the development and use of quantitative methods has contributed to the same objectives as the more qualitative type of research in the establishment of the chemical natures of the vitamins and even in pointing t o the existence of vitamins hitherto undiscovered. Other quantitative aspects of vitamin research seek to ascertain what amounts or proportions yield the best results in nutrition; and to what extent i t is possible, through quantitative adjustments of these and other nutritional factors, to improve an already normal condition of nutrition and health.
THEPROBLEM OF THE OPTIMUM Some of the vitamins have been found to differ from previously studied nutrients in that they continue to yield
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increasingly beneficial results in nutrition when given in successively larger amounts up to several fold the quantities which are demonstrably necessary to provide for normal growth in the young and t o protect against any sign of specific deficiency in the young or in the adult. Mellanby and Green in England reported increasingly beneficial results fIom increments of vitamin A or its precursor up to about fourfold the intake demonstrably needed; and Batchelder in our laboratory, in a different type of experimentation with vitamin A, finds a similar relationship. dpparently a somewhat analogous situation exists in the case of vitamin C, if we correctly understand the clinical observations recently reported by Dalldorf. Experiments of Ellis in our laboratory show that also in the case of vitamin G there is increasing benefit from increments of intake up to much higher levels than suffice to meet minimal needs. Thus for at least some of the vitamins there are wide differences between the level of intake which meets the actual or directly demonstrable nutritional need and that which gives the best results. Along with this finding has come another: A status of nutrition and health which is already normal may still be significantly improved by such quantitative adjustments of the food supply as result in enriching the intake of certain of its chemical factors. These findings stand in distinct contrast to some previous modes of thought. Thus by many it has been regarded as an established fact that the body cannot make good use of more than a slight margin of nutriment above the minimum amount which it clearly and demonstrably needs. But we now see that we must discriminate sharply in this respect between the different chemical factors of nutritional intake. Of fuel food it is true that the optimal intake is close to the actual need; of protein and some of the mineral elements, we regard a margin of something of the order of 50 per cent as a desirable sort of insurance. But now we find that of some of the vitamins the desirable margin is of a higher order, and the resulting benefits seem to be not merely of the nature of insurance or the correction of some slight and hidden deficiency, but rather a constructive advance. Here chemistry, through nutrition, now seems to offer an opportunity to add to the physico-chemical regulatory processes of the animal inheritance the resources of scientific knowledge and research for the further improvement of the body’s internal environment and its consistent maintenance in such condition as may be found most favorable for the varied activities of life. RBCSIVEDMarch 13, 1934.
