auring the 75 years of the American Chemical Society I
I
THIS IS THE SECOND IN A SERIES OF HISTORICAL PAPERS WHICH HAVE BEEN PREPARED IN COMMEMORATION OF THE 15TH ANNIVERSARY OF THE AMERICAN CHEMICAL X x l E l Y
AGRICULTURE, FOOD, NUTRITION. PESTICIDES, AND FERMENTATION
ARE ALL INCLUDED WITHIN ITS BROAD KEN INTRODUCnON
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in 1935,when Zimmerman and Wilcoxon discovered that several synthetic compounds, when applied to plants, bring about effecta that ace qualitatively indistinguishable from those of naturally occurring hormones. Indoleacetic, indolebutyric, naphthaleneacetic, dichlorophenoxyacetic, naphthoxyacetic, phenylacetic. and indolepropionic acids are some of the compounds now useful in this field. Uses of plant hormones include the rooting of cuttings, thinning of fruit blossoms, controlling of p r e h e a t drop of fruits, as aids to fruit set and seedless fruit production, treating seeds, breaking or inducing of dormancy, and chemical modification of existing plant varieties. Plant Breeding Studies. Tremendoua research activity has chsracterised this field. The utilitarian value of increased yield, resistance to disease, higher content of certain valuable constituents, and better quality has stimulated the cooperative approach by the plant breeder, the geneticist, and the chemist, who evaluate the progress that has been made in improving the compasition or nutritive value of new plant varieties. Vegetable Composition. In recent years, much attention har F. C. BLANCK been given to the vitamin and mineral content of vegetables, with special reference to the influence of variety, climate, and fertilizer practices on their constituents. Because vitamin C is N 1926, the late C. A. Browne published a scholarly and comreadily determinable, most of the studies have followed the prehensive report on the progress of agriculieultural chemistry development of this vitamin. They have shown that variety from its earliest American period to 1926, the date of the 50th anniversary of the founding of the AMERICAN CAEMICAL SOCIETT. and climate (light) exert a significant effect on the ascorbic acid content of vegetables, but that differences in fertilizers and soil In this paper, the pioneering work of numerous investigators conditions have little practical significance. With other vitawas inspiringly discussed. I n addition, attention was givcn to mias, the studies have also shown that the location andlor the advances in the chemistry of fertilizers, animal nutrition, season greatly inEuence the amounts of carotene, riboflavin, dairy products, crops, insecticides, fungicides, f w d technology, and thiamine in plant materials. and food control. Maturity Standards. . It has long been known that the maxiI n the section 'that immediately follows, attention has been mum nutritional value and palatability of many raw foods, nofocused on newer fields and applications. The earlier interest tably fruits, were reached at the point of maximum maturity. in individual agricultural commodities has not lessened. I n fact, For many years, a concerted attack has been made on this probthere has been B steady increase in our stare of knowledge, lem, particularly by the application of chemical methods to particularly since the development of new research h l s and determine the changes taking place in growing producta from un procedures. early stage to the point of recognized optimum maturity. This plsnt Hormones. The word "hormone" was 6mt used by the animal physiologist, Starling, in 1905. The original concept has resulted in the development of a numher'of maturity standthat hormones are chemical substanoas made in one part of a n ards which have been valuable in providing food i t e m of organism and transported to other parta where they produce maximum acceptability. Hydrogen Ion Concentration. The development of the p H their e5ecta (Starling) bas been broadened t o include the fact scale is based on the theory of electrolytic djeaociation (Arrhenius, that they are effectivein very minute amounts. In plant biology, the term hormone was extended still further 1887), and the scale now in use was devieed by Sorensen (1909).
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HEMISTRY has alwaya been interested in the problems of agriculture and food. Man's food, clothing, and shelter all come from the soil. Many new branches of science have developed to study special phases of the over-all problem. Nevertheless, the contributions of the 'chemist to the elucidation of these questions have been outstanding and will continue to be 80. Chemistry can no longer be considered a science which stands by itself, but rather as an essential tool in man's effort to develop those resources BO necessary to his welfare, happiness, and health. The extreme breadth of the field of agriculture and food makes i t necessary to c o n h e our review of the past 75 years of progress to those areas which will not conflict with the reports of more specialiaed divisiona.
Agricufiureand 3uud
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Coordinator: F. C. Blanck, Mellon Institute of Industrial Research, Pittsburgh, Pa.
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The application of this new technique to foods and their processing has received great attention in the past 25 to 30 years. Milk, flour, dough, bread, crackers, fruit jellies, canned foods, sea food, discoloration of food in metal containers, and corrosion of metal containers are segments of the food field in which the measurement of p H has been important. I n fact, this determination is now a routine operation in modern food processing plants. Ion Exchange. Ion exchange, defined by Walton (1941) “as a reversible interchange of ions between a liquid phase and a solid body which does not involve any radical change in the solid structure,” was observed by Way (1850) in the passage of potassium chloride solution through soil. The cation exchangers are of three types: (1) aluminosilicates, (2) sulfonated coals, and (3) resinous cation exchangers. The anion exchangers are all organic mines. Ion exchangers are particularly suitable for the concentration of valuable ions present in such small amounts in solution that they cannot be recovered economically by precipitation or evaporation. I n many laboratory applications as well as in the food field, they are valuable. Ion exchange has been used in the preparation of apple sirup, recovery of tartaric acid from grape wastes, recovery of citric acid and sugar sirups from pineapple wastes and of pectin from grapefruit peel, readjustment of salts in milk, removal of nonsugar solids in sucrose production, and removal of organic impurities which contribute to color formation in starch conversion products during storage. Removal of ash from corn sugar liquor by ion exchange methods has made possible the recovery of more dextrose. Antioxidants. The development of rancidity in edible fats and oils and food products containing them has long been a problem of commercial and economic importance. Within the past 10 years, this situation has been attacked with renewed vigor. As a result, there are now available a number of compounds of proved value, especially when employed with certain fats. (Nordihydroguaiaretic acid (N.D.G.A.), Tenox I1 (butylated hydroxyanisol plus propyl gallate plus citric acid), lauryl gallate, fat-soluble esters of ascorbic acid, CY-tocopherol,gum guaiac, and oat flours have been employed either singly or in combination to delay the development of rancidity in fatty foods. More detailed discussion of this subject will be found in the historical treatment of advances in fats and oils. Canning. A major method of food preservation is canning. Introduced into this country in 1819-20, it did not become widespread until the use of tin containers in 1840. The closed, steam-pressure retort or autoclave w m patented in 1874. By 1918-20 the use of the sanitary style of can for fruits and vegetables became practically universal. The period 1923-28 marked the development of a method for the mathematical calculation of adequate heat processes for canned foods from physical and bacteriological data. I n 1937, electrolytic tinning was introduced, followed by the first commercial production of electrolytic tin plate. I n recent years, the development of the high-temperature, short-time method of sterilization gives promise of even higher quality of the finished product. Dehydration. The preservation of foods by drying is one of the oldest food processes known. It was not until World War I that commercial dehydration other than sun drying reached any magnitude in this country. Because of the compacthess of dehydrated foods and their savings of space and containers, considerable effort was expended during that period in developing commercial dehydration. These efforts were unsuccessful because certain fundamental procedures were not understood. The products deteriorated rapidly, were difficult t o reconstitute, and were not particularly acceptable as prepared food items. In World War 11, dehydration again came to the forefront. It was recognized that the blanching or adequate heat treatment of vegetables was necessary to inactivate enzymes before proceeding with the dehydration technique. It was further learned that the
Research worker studies how chemical nutrients affect young apple trees grown in pots of sand
Scientist investigates the action of boron, copper, manganese, and zinc on growth of tung trees
Extraction i s employed in analyzing milk f r o m cows that were fed specially treated forage crops 565
Department of Agriculture scientist studies the recovery of tartaric acid f r o m grape waste
Mojonnier evaporator is used in Production orange juice concentrate at California plant
Of
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packaging of a number of dehydrated items in hermetically sealed containers in the presence of an inert gas such as nitrogen or carbon dioxide not only increased the life of the dehydrated product but also permitted better retention of nutrients. A further advance was made by limiting the moisture content to the iowest possible amount consistent with large scale commercial operations. During World War I1 and in the present feeding program for our armed forces, dehydrated soups occupy an important position. These soups are usually precooked before dehydration to a powder. Such soups reconstitute readily and yield an acceptable food item. Freezing Concentration of Juices. This new development ot the past 3 years is the most spectacular and important contribution t o food technology in the past 10 to 15 years. This has been made possible by the development of new types of equipment which utilize very high vacua without additional application of heat. I n practice, the fruit juices, notably orange juice, are concentrated to approximately one quarter of their volJme and then sufficient fresh juice is added to impart additional flavor. The finished product represents a final concentration of 4 to E and is packed in tin containers which must a t all times be kept in a frozen state during storage, The spectacular increase in production and consumption of this new type of product is well illustrated by the fact that in 1950 the total production amounted to 25,000,000 gallons. Quality Evaluation of Foods. Today, more than ever, the consuming public is alive t o the importance of food quality. Consequently within the past 10 t o 15 years, increased attention has been given to this phase of food technology. W'herevcr possible, suitable chemical, physical, and organoleptic tests are utilized t o determine the acceptability of the many different types of food now available to the American public. Nutritive Value of Foods. With the development of our knowledge of nutrition and more particularly the development oi quantitative methods for the determination of food nutrientb. including vitamins and amino acids, increasing attention is being paid by food processors to the retention of these values in processed foods. The raw materials must be followed through every step in the manufacturing operation in order t o determine points at which nutrient losses may occur, and take appropriate steps to eliminate or a t least substantially reduce such losses. Food Deterioration and Spoilage. Since man's first eFFort to preserve foods, he has been plagued with problems incidental to food deterioration and spoilage. While such changes, particularly spoilage, are primarily microbiological in character, such deterioration and spoilage are frequently accompanied by the development of specific chemical compounds, the isolation and identification of which are accepted as prima facie evidence of spoilage or decomposition. As chemical methods becomr more refined and are suitable for microdetermination, further progress will be made in applying microanalysis to the problems of food spoilage and decomposition. Regulatory Control of Foods. The passage of the Food and Drug Act of 1906 marked a milestone in the better protection of the consuming public against the adulteration and misbranding of foods. However, experirnce showed many n-ealmesses in the old law which reduced its value as a protective measure. Consequently, in 1938 Congress enacted the Food, Drug and Cosmetic Act, which represents a most important advance in the legal control of the purity and labeling of our foods. Perhaps its most outstanding feature is the provision whereby definitions and standards for foods, having the full force of law, can be promulgated. I n all definitions and standards so far announced, full advantage is taken of the use of chemical methods in determining the minimum content of the essential ingredients in such defined food products. We have learned much about the composition of food and agricultural raw materials, the factor# influencing their growth
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INDUSTRIAL AND ENGINEERING CHEMISTRY
and chemical make-up, their transformations to new uses, the development of new chemicals to meet the needs of agriculture, and the improvement of the purity and quality of our foods. There is still much more t o learn. Browne stated 25 years ago: “Chemistry in its relationship t o agriculture has changed from an independent t o a cooperative science, and it is in the borderland where [agricultural chemistry] and the other sciences meet t h a t the agricultural scientists of the future will find the greatest opportunities for service and accomplishment.’ ’
flutritiuM
E. V. MCCOLLUM
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ROGRESS in the investigation of mammalian nutrition before 1875 is mainly associated with the names of Lavoisier,
Gay-Lussac, Liebig, Boussingitult, Mulder, Schmidt, Bidder, Regnault, Reiset, Bachl, Moleschott, Voit, Stohman, Magendie, Henneberg, Rubner, and others who worked under the guidance Qf these pioneers. The principal facts which were established by their work were: Metabolism of food involves oxidation. There are relationshi s between food, work, and heat production. $he nitrogen content of the urine can be. used as a measure of rotein metabolism in the body, as proteins contain nitrogen a n 8 no significant amounts of nitrogen are excreted in respiration and the shedding of epidermal structures. Analyses had been made of a number of foods and feeding stuffs which revealed their content of carbon, hydrogen, nitrogen, and oxygen. Henneberg and Stohmmn had developed their method by which the moisture, ash, nitrogen (protein), nitrogenfree extract, and crude fiber were determned. This formed the basis of food analyses for many years. Energy for muscular work can be derived from carbohydrate and fat as well as protein, and the latter is taken from muscle substance only after nonnitrogenous reserves are exhausted. Muscular work does not lead t o increased nitrogen excretion in the urine. Results of respiration studies revealed the significance of the respiratory quotient as a means for determining the kind of nutrient being burned for energy and the k i d of reserve material beiug stored from ingested foods. Stohmann had determined the calorific values of fats, fatty acids, certain proteins, several sugars, urea, and other metabolic products. It had been shown that animals cannot be maintained in health when restricted t o EL single nutrient such as sugar, albumin, gelatin, or olive oil. Some attention had been given to determining the physiological significance of inorganic salts, acidity, and the maintenance of neutrality in the body.
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Progress in Research Since 1875. During the last quarter of the nineteenth century, W. A. Atwater analyzed all of the more important human foods of the United States, using the “Weende method” devised by Henneberg and Stohmann. Atwater determined the caloric values of foods and, in many cases, their digestibility. With a respiration calorimeter, he determined the energy requirements of human subjects doing several kinds of work. He wm the leader in making dietary surveys designed t o discover the consumption of protein and calories of people of many different occupations and many different economic circumstances. H e recommended the purchase of foods on the bmis of the cost of the protein and energy which these foods provided. Contriiutions of Agricultural Experiment Stations. The first agrioultural experiment station wm established at Weende, near Gottingen, Germany, in 1857. There Henneberg, von Wolff, and Stohmann set the pattern for experiments in animal nutrition, with the objective of achieving economic animal production. The scientific questions which these experimentors asked theQ-
8.V.
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selves were: What are the specific nutrients in different feeding stuffs, in what proportions do they occur in each, and in what PrbPortions must the nutritive ingredients be fed in order to produce from the minimum of feed the maximum of flesh (lean), fat, or both? Their investigations covered methods of analysis, digestibility, and the nutritive effects as shown by experience in feeding. Henneberg soon reached the conclusion that without the aid Of respiration experiments the laws underlying the formation of flesh and fat could not be worked out conclusively. H e constructed a respiration apparatus similar t o the one which had been built a short time before by Pettenkofer and Voit a t Munich for the study of the metabolism of carnivorous animals. Atwater and Rosa in America built the first such apparatus for the study of human nutrition, and Armsby built one for the study of the metabolism of cattle. I n 1884 Boussingault published his “Economie Rurale,” in which he described his studies on the relation between the content of albuminous matter and food consumed and the growth of farm animals. In 1847 Laws and Gilbert began their studies of animal production a t Rothamsted. ’These studies were imitated by animal husbandrymen and agricultural chemists everywhere until about 1920. The fact early emerged that there were marked discrepancies between the chemical composition of feeds and their animal weight production values as tested by feeding. By 1889 this fact was so glaringly apparent that a committee of the Association of Official Agricultural Chemists in that year issued a report on the shortcomings of the standard methods for food and feed analysis, The members agreed that efforts should be directed toward devising methods which would reveal the natures and amounts of individual chemical substances in natural products. Little progress was made in this direction until after 1900, although many new chemical substances were isolated from plant and animal materials. As the nutritive significance of none of these was known, the discoveries disclosed nothing new in nutrition. What was needed was a new approach to the study of the nutritive constituents of foods. The objective of learning the nature of every constituent of plant and animal tissues was admirable, but it was still more important to discover those substances, well characterized chemically, which a diet must provide in order t o support the normal physiological needs of the animal. It was also necessary t o determine the proportions in which these substances should be supplied to secure best results. Chemical studies could never provide such information. It was necessary t o combine chemical studies with animal feeding tests in which basal diets, simplified as far as possible, were used. So far as could be realized, the chemical compositions of these diets had to be known in terms of final digestion products. Between 1898 and 1906, no less than twenty studies were published, describing attempts t o nourish animals on mixtures of purified proteins, carbohydrates, fats, and mixtures of inorganic salts. Those of Pekelharing (1905) and of Wilcock and Hopkins (1906) were especially noteworthy. Although these “synthetic” diets provided everything which food chemists thought significant, their animals failed. These investigators found that failing animals could be improved greatly by the inclusion in the experimental diet of a small amount of whole milk solids. These studies made i t apparent that there existed nutrients of which chemists knew nothing a t all and that these were not furnished by diets composed exclusively of the recognized classes of nutrients. Studies on Beriberi. Eijkman produced polyneuritis in birds by restricting them t o a diet of polished rice and then cured the disease with extracts of rice polishings. These experiments were soon followed by the work of Vordermann oq the substitution of
McCollum, Johns Hopkins University, Baltimore, Md.
lT,ho]e,.ice for polished rice in the diets of prisoner? anti inmatw of a,sy]ums. Together, these studies ushered in a ncw era in nut& tional investigations. The notable studies of Kossel on the basic amino acids and tihe equally important studies of E. Fischer (1900 to 1910) 011 tjhe composition of protein hydrolysates (work n-hich was greatly extended by T. R. Osborne, E. Abderhalden, and others) brought to light the great differences in the amino acid make-up of prot,eins from different sources and ext,ended t,he list of known amino acids which result from protein hydrolysis. These results led t,o the important conclusion that in animal nutrition it is not permissible t,o speak of the ”protein moiety” of any diet as coniparable to that of another diet derived from different plant and animal sources. Instead, the amino acid composition was reC(Jgnized a,s the important property. W, C. Iloso demonstrat>ed that only t’en of the amino a’cidsresulting from protein digestiou arc indispensable t o the nutrition of the rat when all other fa(:t,ors of a normal diet are provided. This finding concluded a long Rerips of studies by Osborne, Rlendel, Abderhalden, and many others who sought, t,o determine the amino acid needs of animals. The Era of Vitamins. In 1906 3’. G. Hopkins expressed the! belief that not, only beriberi but also such disorders as scurvy a,nd rickets were caused by a tldiciency of hitherto unsuspectd nut,rient,s. Pekalharing had come to t,he same conclusion thtA preceding year on the hasis of his observations of the pattrological effects of rewicting aninials t o a diet, of purified food substances. In 1913 McCollum and Davis demonstrated thal, certain fats cont,ain an essent,ial nutrient, not contained in other fa,ts. This \vas the first demonstration of a fat,-soluble unknowli important in mammalian nut,rition. Funk, whose speculations on t h e nutritional origin of several pathological stat- extended t,how of Pelralharing and Hopkins, coined the term “vitttmin” in 1911 to include all such unknown nutrients. Organic us. Inorganic Phosphorus in Nutrition. Hetwrcn 1895 a,nd 1910 there was a widespread belief that organic compounds containing phosphorus might be important, in nutrit,ion, because the ahility of the body to synthesize comples suhstances of thip type was questioned. The problem xas solvcd by the cxperixnents of Hart, McCollum, and Fuller (1909), who showed that inorganic salts of orthophosphoric acid could serve all the purposes of mammalian nut,rition, including the synthesis of phospholipins, phosphoproteins, and nucleic acids. This conclusion was supported by the studies of Plimmer (1909, 1913), who demonstrated that for ea,ch of thew types of organic phosphoruii compounds, all of Rhich are prominent in animal and plant mat,erials, there are enzymes in the digestive fluids and tissue* which bring about their hydrolysis. Therefore, even when they are t,aken with food, they are resolved before absorption intis orthophoephoric acid and the respective organic components. Development of Biological Method for Analysis of a Foodstuff. For mow t,han a century, medical literature had contained proof that scurvy could be prevented and cured by the consumption of fresh vegetables or infusions (Kramer, 1720) and that beribcri could be eradicated by alteration of the diet (Talraki, 18821. The studies on animals made by Eijkman, Pekelharing, arid Hopkins extended the proof t,hat, pathological conditions could he induced by deficient, diets. Nevertheless, the idea was only slowly accepted that food constit,uents other than those routinely estimated by analytical chemists viere of physiological significance. Froin 1909 t o 1913, Osborne and hlendel, using a diet composed o f purified food substances together with 28.3% of dried, del~roteinated whey, secured results with growing rats which revealed astonishing differences in the nutrit,ive values of proteins from different sources and emphasized the practical significance of a deficiency of lysine and tryptophan in the proteins of cereals. Not until they had confirmed the observation of McCollum and Davis respecting the presence in butter fat and egg yolk fat of some substance indispensa,ble to nutrition but not found in
Rabbits a w j’m‘ manganpsp dietary supplewwnt to detwminc. i t s effect on anzmal growth
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Inadequate diet has resulted in the below-average growth of laboratory rut ut thP right 568
March 1951
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I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
lard or olive oil, did they accept the view that there were undiscovered nutrients of the class now known as vitamins. There was a sharp turn in the thinking of experimenters in animal nutrition upon the publication of McCollum and Davis’ procedure for revealing the nature of the dietary deficiencies of individual foodstuffs. This biological method of inquiry into the reasons for observed nutritive failure of animals on a n experimental diet may be illustrated by their study of the feeding of wheat kernel t o young rats. When wheat was the sole food: no growth, short life. Wheat plus a purified protein (source of amino acids): no growth, short life. Wheat plus a salt mixture which gave it a mineral content similar t o t h a t of milk: very little growth. Wheat plus a growthpromoting fat (butter fat): no growth. From these results, it was apparent t h a t more than one nutritive factor was involved in determining the inadequacy of wheat as a food. Supplementing wheat with two kinds of nutrients gave the following results: Wheat plus a protein, plus the salt mixture: good growth for a time, few or no young, short life. Wheat plus protein, plus a growth-promoting fat: no growth, short life. Wheat plus the salt mixture, plus the growthpromoting fat: fair growth for a time, few or no young. short life. When young rats were fed wheat plus all three kinds of supplements, the results were good growth, normal number of young, success in rearing young, life approximately the normal span. I n 1915 McCollum and Davis carried out a series of experiments with polished rice supplemented with a purified protein, a salt mixture, and a growth-promoting fat. The three types of supplements were not effective in sustaining growth or maintaining life beyond a few weeks. But when the three supplements were given along with polished rice and a small addition of wheat germ or a n alcoholic or water extract of germ, growth and reproduction of the rat were normal. Thus it was shown that for normal growth and reproduction two nutrients of unidentified nature-one soluble in fats and associated with fats in foods, the other insoluble in fats but soluble in water and in alcohol-are indispensable. This water-soluble factor was in later years shown t o contain several components. These studies at once turned nutrition studies in a new direction. During the next decade Morgan published a 8core of papers on the biological analysis of various foods. Osborne and Mendel abandoned their former techniques and studied the shortcomings of a considerable variety of natural foods by the new procedure, the biological method, which supplemented t,he chemical methods of food analysis. Prevention of Infantile Scurvy. By 1890 there was a grow ng appreciation of the role of raw milk in transmitting typhoid fever, scarlet fever, septic sore throat, and bovine tuberculosis. Pasteurization, which rendered milk safe that had been infected previously .by dangerous human contact, was strongly recommended by the medical profession. Accordingly, pasteurization ordinances were adopted in progressive cities. These proved a blessing to the adult population, but brought tragedy to bottlefed infants who were fed a boiled milk formula or pasteurized milk and generally barley water. The danger of restricting infants to a cooked formula was not understood. I n 1912 Holst and Froelich in Oslo showed t h a t a diet consisting exclusively of cooked or dried foods would induce scurvy in guinea pigs and that fresh uncooked vegetable food would cure the disease. A. F. Iless (1915) applied the new knowledge t o infant feeding. H e was very active in teaching the medical profession and mothers the necessity of giving the bottle-fed infant some fresh fruit juice daily to protect it against scurvy. This has now become universal practice. Prevention of Rickets in Children. Cod liver oil had been employed as a remedy for rickets for many years. Beginning in
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1918 Mellfinby showed its effectiveness in the treatment of experimental rickets in pups. Sherman and Pappenheimer noted t h a t a change in the phosphate content of a diet largely composed of white flour might cause healing of rickets in rats. McCoHum, Park, and associates showed what characteristics of a diet would cause acute and severe rickets in young rats. With the experimentally induced disease they were able in 1922 t o demonstrate that a second-fat-soluble vitamin (vitamin D) is present in cod liver oil. I n 1925 Steenbock and A. F. Hess independently discovered that exposure of a rickets-producing diet t o ultraviolet rays generated vitamin D. They showed that the precursor of vitamin D which was activated by light is a sterol. Discovery of Etiology of Pellagra. Between 1913 and 1926, J. Goldberger conducted nunieraus studies which revealed that pellegra is caused by a dietary deficiency, and described the effectivenessof various foods in preventing the disease. I n 1938 Elvehjem and associates discovered that nicotinic acid or its amide would cure black tongue in dogs. Spies and associates confirmed its curative value in human pellagra. Discovery and Synthesis of Other Vitamins. R. R. ’IVilliams isolated from rice polishings a large sample of the antineuritic vitamin, now called B1 or thiamine. Study of this material resulted in its synthesis (1937). R. J. Williams (1933) discovered pantothenic acid. Pyridoxine (vitamin BB)was discovered by Gyorgy (1934). Among many other important vitamin discoveries were riboflavin, biotin, vitamin E, vitamin K, ascorbic acid, and vitamin BIS. Essential Fatty Acids. I n 1932 Burr and Burr demonstrated that linoleic or linolenic acid must be supplied in the diet of rats to prevent the symptoms of the “fat-deficiency syndrome.” Lipotrophic Factors. In 1932 Best and others demonstrated the lipotrophic property of choline. I n 1935 Best and Huntsman showed that casein possesses lipotrophic properties, which were traced by Tucker and Eckstein (1937) t o the amino acid methionine. Trace Elements. In 1925 Hart demonstrated the nutritional significance of copper. Later investigators have discovered that manganese, zinc, and cobalt arc indispensable nutrients. . From the standpoint of human welfare, the discoveries t h a t have been made during the past decades in the field of food and nutrition have been a t least as significant as those in the field of preventive and clinical medicine.
H. L. HALLER
A
LTHOUGH some of the pesticides of today were known t o have value centuries ago, extensive use of effective insecticides and fungicides had its beginning only a few years before the founding of the AMERICANCHEMICAL SOCIETY. About 1860 several developments made agriculturists in the United States more conscious of the need of insect control. Probably the most important of these was the sudden appearance of the Colorado potato beetle as a n economic problem. This insect, native t o the eastern slopes of the Rocky Mountains, where it had previously fed on wild solanaceous plants, found the potato a particularly acceptable food when the westward spread of potato culture brought t h a t important crop plant within its reach. Paris green was found t o be highly effective against this beetle, and by 1870 was used widely as an agricultural insecticide. Within a few years, London purple became available, and from 1880 to 1900 these two chemicals were the most commonly used insecticides. However, the composition of London purple was
H. L. Haller, Bureau of Entomology and Plant Quarantine, U. S. Department of Agriculture, Washington, D. C.
variable; some lots might be satisfactory, whereas others contained sufficient water-soluble arsenic t o cause foliage injury. Paris green also burned foliage. Moreover, it is a heavy powder, it settles rapidly from suspensions, and has poor adhesive properties. Thus the need for insecticides having better physical and chemical properties was evident. Emphasis then was on arseniccontaining insecticides, and in 1892 lead arsenate was prepared for the first time. The superiority of lead arsenate over other insecticides was soon demonstrated, and by 1910 it had largely replaced Paris green and London purple. Until displaced by DDT and Parathion shortly after the end of World War 11, lead arsenate was more extensively used against orchard pests than any other insecticide. I n 1920 about 30,000,000 pounds were used. The annual usage increased to about 80,000,000 pounds in 1945. Inorganic fluorine compounds have also been employed as insecticides for a long time, sodium fluoride probably being the first. I n 1896 a British patent covering several fluorides, fluosilicates, and borofluosilicates was issued. Sodium aluminum fluosilicate is widely sold today as a mothproofing agent, while sodium fluoaluminate (cryolite) serves as an agricultural insecticide. Oils have been used as insecticides for hundreds of year*, but not until the latter half of the nineteenth century were systematic studies undertaken to determinr their value in insect control. On horticultural crops, oils serve as dormant sprays against scale insects, mites, insect eggs, and certain hibernating caterpillars; as additives to increase the effectiveness of other insecticides; and ab carriers for many iusrcticidal chemicals. I n 1865 kerosene was recommended for t h r control of scale insects on orange trees. Because undiluted kerosene severely injured foliage arid fruit, emulsions of oil in water, produced a t first merely by violent mechanic%lagitation and later with the aid of soap as an emulsifying agent, were substituted. Kerosene was gradually replaced by crude oils and eventually by lubricating oils. The development of oil sprays was temporaiily retarded by the introduction, in about 1900, of lime-sulfur solution as a more effective spray for the control of scale insects. However, interest was renewed about 1923 when the superiority of light lubricating oil emulsion over lime-sulfur for control of the 8an Jose scale was demonstrated, Some of the progress that has been made in the use of oils as insecticides was reviewed a t the Symposium on Agricultural Applications of Petroleum Products held a t the September 1950 meeting of the AMERICAN CHEMICAL SOCIETY in Chicago. Another important class of pesticides is fumigants, which were also among the first insecticides used by man. Burning sulfur was probably the oldest fumigant. Today many volatile insecticides are in general use. Until the early 1920’5, hydrogen cyanide and carbon disulfide were the most important commercial fumigants. Hydrogen cyanide was originally developed for the controI of scale insects on citrus. Carbon disulfide found wide use as a grain fumigant. Although efficacious, it is flammable and its vapor when mixed with air is highly explosive. After representatives of leading railway systems had recommended that the United States Department of Agriculture find a substitute for carbon disulfide, many volatile compounds were tested. A number of highly effective products were developed, among which are methyl bromide, ethylene dichloride, ethylene dibromide, ethylene oxide, and dichloropropane-dichloropropene. Progress in the development of fungicides has paralleled that of insecticides. Copper and sulfur, the oldest and still the most widely used fungicides, have felt the inroads of organic compounds. Combinations of copper sulfate and lime have been used since 1870, but it was not until about 1885 that Millardet exploited the use of Bordeaux mixture. As a result of recent investigations, fixed copper fungicides are standard products for the control of a number of plant diseases.
Healthy snap beans (left) were treated with insecticide. Untreated plants (right) were badly damaged by beetles
Untreated leather camera case (left) was severely attacked by fungi. Treated case (right) was undamaged 570
The early 1930’s saw the development of derivatives of thiuram disulfide and dithiocarbamates as fungicides, both of which are used commercially. Extensive explorations have also been made among organic compounds t o find products suitable as seed protectants of cereal, field, and vegetable crops. Organic mercury-containing compounds have been found very effective, as has chloranil. The passage in 1887 of the Hatch Agricultural Experiment Station Act establishing state experiment stations made possible more intensive studies of insecticides, fungicides, and other pesticides. I n 1896 the U. S. Department of Agriculture assigned J. K. Haywood, a chemist, to work on insecticides. H e and E. D. Sanderson, chairman of a standing commitee on proprietary insecticides of the American Association of Economic Entomologists, were largely responsible for the writing and passage of the Insecticide Act of 1910. This act was designed t o prevent t h e manufacture, sale, or transportation in interstate commerce of adulterated or misbranded insecticides and fungicides, and t o prevent the importation of such articles into the United States. i n 1947 the Federal Insecticide, Fungicide, and Rodenticide Act was passed. This act, which repeals the Insecticide Act of 1910, regulates the marketing of economic poisons and devices. I n addition t o the federal act, 38 states have laws regulating the _. . sale of pesticides.
House Jlies are scientifial@ bred before they are placed in lethal chamber used in testing insect .sprays
NEW COMPOUNDS
By 1910 agricultural practices had become more intensified, and insect populations increased, as did the losses they caused to many important crops. People began t o realize t h a t a n adequate supply of food and feed was impossible without the use of insecticides and fungicides. The war against insects and fungi became world-wide. Studies b y state and federal workers were supplemented by those carried out in the laboratories of our large chemical and oil companies and nonprofit institutions. Soon after World War I, many synthetic organic chemicals became available, for which a use was being sought. Their availability, together with the growing concern about t h e health hazards from toxic residues on sprayed fruits and vegetables, shifted the trend in the development of new insecticides from inorganic to organic compounds. I n the early 1920’s numerous compounds related t o nicotine were tested. In 1924 six comprehensive articles were published on the structure of the active principles of pyrethrum flowers. They exert a rapid paralytical, or knockdown, effect upon many insects, a characteristic not shown by any of the newer insecticides. Rapid removal or destruction of disease-carrying insects is especially desirable, and pyrethrum is most effective against such insects, as well as household pests. Those six articles published in 1924 provided fundamental information on the structures of the pyrethrins. It was not until 1947, however, t h a t t h e detailed structures of these complex compounds were determined with certainty. Originally i t was believed t h a t pyrethrum contained two active principles, pyrethrin 1 and pyrethrin 11. Intensive studies b y F. B. LaForge and his associates of t h e Bureau of Entomology and Plant Quarantine over about 15 years revealed the presence of two other active principles closely related t o the pyrethrins. They have been designated as cinerin I and cinerin 11. Following the determination of the exact structures of the pyrethrins and the cinerins, their syntheses, as well as t h a t of closely related compounds, were undertaken by these workers. Early in 1949 the stereoisomer of cinerolone was synthesized. When esterified with chrysanthemum monocarboxylic acid, this stereoisomer furnished a n isomer of cinerin I, which was as insecticidal as t h e natural ester to houseflies and other insects. T h e synthesis of homologs of cinerin I followed. One of them showed outstanding toxicity to insects. It was first called t h e allyl homolog of cinerin I
Chemist transfers to small bottles the insecticide he has purified and mixed with a suitable carrier
Machine makes possible the rapid, large-scale spraying of potato .field i n Aroostook County, M e .
Y
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I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
1, but recently has been given the coined name, allethrin. \\i'ithin a year after the synthesis of the pyrethrinlike esters was announced, allethrin was in conimercial production. This is an outstanding accomplishment, especially when it is considered that its preparation requires at least twelve chemical steps, each ntep necessitating careful chemical control to ensure a good product and maximum yield. Industry is to be congratulnted for having done a fine job in so short a time. Several years before Pearl Harbor it was apparent that in the w e n t of a Tar there weuld be a shortage of pyrethrum Effort6 were therefore directed toward finding products that \+auld replace part of the pyrethrinc without decreasing their insecticidal value. I n about 1940 the discovery was made that sesame oil incieased the tovicitv of the pyrethrins. The effectiveness of sesamin, the activc. ingredient, mas shown to he due i o the presence of the methylene dioxyphenyl grouping. Nuiiierous compounds containing this grouping were prepared Among the commercial products that have been developed are piperonyl cyclonene, piperonyl butouide, and n-propyl isonie. An intensive study of the structure of rotenone, initiated about 1928 independently and almost simultaneously in Germany, Japan, and this country, culiniriated in the 13eteiminati0n of ita structure late in 1931. The discovery of DUT revolutionized work on insecticides. Within a short time, several chemically unrelated chlorinated hT.drocarbons-benwpne heuachloride, chlordan and toxaphenewere also found t o have outstanding insecticidal properties. Vore recently devera1 organic phosphorus-containing compounds have merited attention as insecticides; amoiig the inore important are parathion, hrsaethyl tetraphosphate. ~ i i dtetraPthyl pvrophosphate. PRODUCT ANALYSIS
The knowledge that an orgaiiic*compound is highll- toxic, to several species of insects does not alone justify its immediate wide scale use. Information must b e obtained as to the effect of the chemical on public health, farm animals, soils, vegetation, beneficial insects including been, and ~ i l d l i f e~vherever these interests are involved. It niurt also he determined ulipther the compound can best be applied as a dust, a spray, or an aerosol. For such determinations, a knowledge of the physical and cheniical characteristics of the product i b needed, including its coniposition, its solubility in various mlvents, and its compatibility with other insecticides, fungicid , arid dust diluents. LIethodq for analysis of the product itsel as well a b in ductfi, in sprA.r.6, and in combination with other insecticides, must be developed. 11~these and many other studies, considerable piogrei';: has been made, and today they are receiving greater attention than w e r before. Recently much progress has also been made ill equipment acrosol and methods of applying insecticides. The so-~~alled iiiethod of insecticide dispersion merits a t least brief diqeussion. Three general types of aerosols are recognized---those produced by mechanical means, those generated thermally, and those that employ a liquefied gas. The last type played a proiniuent role during the war in controlling flying insects, suc+h HZ diseasecarrying mosquitoes and flies. Approximatel) 35,000,000 1 -pound aerosol bombs containing pyrethrum evtract a i d sesame oil dissolved in dichlorodifluoromethane were mar1uf:rcture.d for our armed forces during the war. hlthough much progress in the development aiid UPP of pesticides has been made during the past 75 years, many problems remain to be solved. The recent hearing of the Food and Drug Administration relative t o the need for pesticides has injected a note of uncertainty as t o the future of some pesticides How-
Vol. 43, No. 3
ever, pesticides are required for the production and protection of our food, feed, and fiber crops, and there is little question that the challenge can he met.
J. C. WARD
T
HE, control of pest anirnals by poison is not a new procedure in this country, for there are records of the use of arsenical\, phosphorus, barium carbonate, and strychnine since about the middle of the nineteenth century. Many improvements in methods and materials, however, have taken place within the past 30 years. Prior to 1920 the iniportance of the pest mammal problem had been emphasized by outbreaks of rat-borne bubonic plague in San Francisco and other coastal cities. There was extensive loss of livestock on thtb western plains from rabies transmitted by coyotes. The need for organized control of mammals which were able t o transmit disease and to do widespread economic damage was well recognized by 1920, even though the chemical agents available rverc. limited to those mentioned above, u i t h the addition of thr cyanides. Research in contiol methods was aiinrd largely at d c a veloping and testing trap3 of vaiinu' kinds, in devising poiwrions mixtures, and in finding more effwtive ~ ~ a to y us v them Shortly after 1920, research \T orlrers in this couritr? learned of three products which had pi eviously been linomn elmvllcw in the world. These were imported for test. The first )
