MAN’S DEEPEST URGE IS TO UNDERSTAND HIMSELF AND HIS PLACE IN THE UNIVERSE AND TO FATHOM HIS OWN NATUREAS A LIVING ORGANISM
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HEMISTRY is the field of science that deals with energy changes, the change of matter from one form to another. Because biological chemistry or physiological chemistry, or biochemistry as it is known now, deals with energy changes, growth, repair, digestion, absorption, elimination, and the effect of various agencies on the phenomena of vital activities, normal and abnormal, it is but natural that biochemistry has loomed’large in the progress of chemistry from its earliest application. According t o Chittenden ( d ) , a course in physiological chemistry w w early established a t the Sheffield Scientific School at Yale University, where Chittenden was appointed professor of physiological chemistry in 1882. This course was designed for the instruction of students who intended to enter medicine. Physiological chemistry was regarded as the branch of chemistry dealing with the composition and reactions of substances having physiological significance, a limited view in the light of present-day studies. In America after 1890 there was a rapid development of physiological chemistry, bound more or less to physiology, which was emerging as an important field of study. I n 1887 the American PSysiological Society was established. Then in 1906 the separate American Society of Biological Chemists was created, and in 1913 a composite society was formed-the Federation of American Societies for Experimental Biology, which included physiology, biochemistry, pharmacology, experimental therapeutics, and experimental pathology. With such a group of societies dealing with biochemistry and related subjects, why was there need for the Division of Biological Chemistry in the AMERICANCHEMICALSOCIETY? All the societies mentioned were, in the main, for specialists in the field of biochemistry and related studies and gave little opportunity for workers in other fields to present their experimental findings of possible value in solving problems of nutrition, physiology, bacteriology, and medicine. Moreover, the interest in biological applications was growing in many lines of chemistry, especially in physical and organic chemistry. I n the Division of Biological Chemistry, it became recognized that there exists a close relationship between all classes of chemical knowledge and that every branch of chemistry could be applied t o the understanding of nature. I n this division, men of. different backgrounds could find a common interest in applying chemistry, physics, bacteriology, electronics, and what not to the eluridation of vital phenomena. And so, the urgent demand of workers in various fields called for the formation of a Division of Biological Chemistry as a separate division in the AMERICAN CHEMICALSOCIETY.Many members of the American Society of Biological Chemists became active in the A.C.S. Division of Biological Chemists. To some degree, the division was a preparation for membership in the more specialized American Society of Biological Chemists. The Division of Biological Chemistry was authorized in 1913. The first chairman was C. L. Alsberg, 1914-17. From the outset, the division was closely related to the Divisions of Agricultural and Food Chemistry and Organic Chemistry, especially the latter. I n fact, some of the leaders in the field of organic chemistry, such as Treat B. Johnson, became interested in biological chemistry. For example, Johnson (1) said in 1926:
M. X. Sullivan, Georgetown University, Wmhin@on, D. C. 589
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“The trend of organic chemistry is gradually toward a consideration of nature as a manipulation of energy. The continuity of all classes of chemical phenomena is being more and more recognized and, as a result, we are seeing the evolution of a new kind of chemistry-biochemistry. This is attracting the attention of some of our best workers in the fields of organic and physical chemistry. I n no country is more progress being made today in this new field of chemical science than in America.” It is a glorious fact that the period 1910 to 1950 was an era of remarkable advance. Much progress was made not only in unraveling complex problems in biochemistry but also in opening u p numerous new lines of attack. I n addition to being an aid to physiology and medicine, biochemistry became a field of independent research aimed a t explaining in chemical terms the action of enzymes and coenzymes, the intermediary metabolism of proteins, carbohydrates, and fats, and the nature of vitamins and antibiotics. New instruments of precision were developed arid applied to the study of all kinds of reactions pertaining to vital phenomena. The organisms under study were increased in number to include bacteria, molds, plants, animals, and man. All this progress did not come suddenly. A firm foundation had been early laid by investigators in Germany, England, and
A number of recent biochemical investigatiom have been greatly simplified by the use of paper chromatography
the United States. Emil Fischer by 1908 had determined the structures of the common sugars and of amino acids and peptides, the building stones of proteins. Albrecht Kossel had made great progress in the purines and pyrimidincs, and so had P. A. Levene in America; Hans Fischer had deciphered the chemical structure of the blood and bile pigments. Frederick G. Hopkins of England had made advances in the field of nutrition. Casimir Funk had added greatly to the vitamin field, while Jacques Loeb in the United States and Otto Warburg in Germany had stressed the fact that life processes could best be understood by a study of what was common to all living species - plant and animal cells. NOTABLE ADVANCES
I n the 37 years since the establishment of the Division of Biological Chemistry, changes have come about in the field mainly through the development of more precise and highly specific tests and through the use of better and better instruments of precision. With no attempt t o cover the advances in detail, the changes can be roughly indicated by the following: 1. Early analysis depended upon the use of relatively large amounts of material and laborious instrumentation. With time, microanalysis came into play with the introduction of microbalances, microapparatus, and other devices. These instruments required only small amounts of chemical substances- -that is, in the quantities that normally occur in living things. 2. I n colorimetric work, early tests were relatively nonspecific and instrumentation was comparatively crude. For example, balanced Nessler tubes were employed in color comparisons. Then came the Duboscq colorimeter. Later, with photoelectric instruments, smaller amounts of material could be estimated. By use of suitable filters, extraneous colors could be eliminated and degrees of change on standing could be followed. Finally came the spectrophotometer, which enabled workers t o estimate a few thousandths of a milligram with high degrees of precision. 3. I n tissue study, early work dealt with tissue in bulk. Modern studies deal with single cells, yeasts, bacteria, and blood corpuscles, and now with portions of a cell nucleus and mitachrondria. Thme investigations have been made possible by the extended use of precise instrumenL9 and by the sharpened outlook of the investigators, who not only accumulated data but also exercised proper judgment in interpreting their research findings. 4. Early work dealt largely with the beginning and end materials of metabolism. Modern work emphasizes intermediate9 and also the enzymes, hormones, vitamins, and minerals involved. Whereas formerly sugar as a substrate and alcohol 01 lactic acid as end products were the main components investigated, now most of the various enzymes and coenzymes involved in sugar metabolism (some 20 or more) have been deciphered Over ten intermediates have been determined. Even the compounds which play a role in muscle contraction have been discovered and isolated. 5. The action of vitamins was but vaguely undcrstood up to 1920. Now many of them have been isolated and synthesized. Considerable knowledge has been obtained regarding their behavior, even their role as coenzymes and their interplay with antivitamins. 6. Enzymes and viruses have been crystallized. Viruses have been found to be high molecular weight nucleoproteins similar to those found in genes-the minute, fundamental, self-reproducing units of heredity. And now work is under way on the chemistry of the genes. 7 . Formerly, carbon dioxide was considered an end produrt of metabolism-a waste product, in fact. Kow, with the help of tracer isotopes, i t has been found t o play a significant role in synthesis. Thus, when carbon dioxide labeled with isotopic carbon is injected into an animal as bicarbonate, some of the labeled carbon is found incorporated in the glycogen of the IiveT.
Biochemist at University of Wisconsin studies oxygen consumption of living cells
Puri$cation of pectin by means of ion-exchange resins i s investigated ut Western Regional Research Laboratory
Standing in front of equipment used to determine rutin in plants, scientist inspects sample f r o m green buckwheat 590
By using tagged elements and suitable detection instruments, such aa Geiger counters, biochemists have made much progress in following the inner workings of the body. As stated by Meyerhof (d), “One may say that the use of isotopes has added a new dimension to biochemical studies; it allows us to follow reactions which cannot be seen by purely chemical means.” The fmt use of tracer isotopes in the investigation of metabolic reactions was made by George Hevesy in 1926 in his study of how plants absorb naturally occurring radioactive lead. By 1929, E. 0. Lawrence had developed the cyclotron, which both he and Milton Livingston utilized to bombard nonradioactive atoms with high-speed particles. Thereby they produced artificial radioactive elements as well aa nonradioactive isotopes. The resulting isotopes made possible the detailed study of complex biochemical changes-transamination, transmethylation, analysis, synthesis, and various intermediary changes. This work increased considerably our knowledge of life processes and revised our interpretation of metabolic activities. In the biological application of isotopes, Rudolph Schoenheimer and David Rittenberg were pioneers. I n 1935, they began their study with deuterostearic acid; in 1937 they fed rats deuterostearic acid and isolated deuteropalmitic acid. Later, in association with other investigators, they employed “6 in the study of protein metabolism. With the aid of isotopes, an interesting finding was made concerning the biological synthesis of cystine. Harold Tarver and Carl Schmidt, using 535 methionine in the diet of rats, found that the hair contained cystine with radioactive sulfur. I n order to determine whether or not methionine contributed the carbon chain to the synthesis of cystine, Vincent duvigneaud and coworkers synthesized and administered methionine labeled with 534 and (313. Cystine isolated from the hair of the rats contained ‘SV4‘but n o C13. With the aid of radioactive sulfur in methionine and tagged carbon in serine, it waa discovered that the formation of cystine in vivo was preceded by the interaction of homocysteine and serine to form cystathionine. The enzymatic splitting of cystathionine resulted in the production of cysteine which w w oxidized to cystine found in the hair. Many other detailed problems-oxidation-reduction, fermentation, polymerization, phosphorylation, photosynthesis, and the synthesis of fatty acids and nitrogen compounds-have been studied with the aid of tagged elements.
Department of Agriculture researcher examines two samples of crystalline tomatine obtained f r o m tomato plants
Photoelectric quartz spectrophotometer i s widely employed in the analgsis of biqchemical compounds
STUDY OF GENETICS
One field of biological chemistry that borders on the philosophical is the field of genetics, which has seen much progress in recent years. “Man’s deepest urge,” said Dobzhansky (5) “is to understand himself and his place in the universe-to fathom his own nature as a living organism and the interactions between heredity and environment that shape the development of his body and mind.” The Austrian monk, Gregor Mendel, founded the science of genetics in 1865 with his work on crossed varieties of peas. Studying the color of the flowers and the shape of the seeds, Mendel concluded that heredity was controlled by distinct units or particles transmitted by both parents to their offspring and reassorted in each generation. With the passage of time and the efforta of many investigators, the genes were found to be particles of chromosomes. Their chemical nature became the subject of intensive investigation. I n America, Alfred E. Mirsky (1943) applied ultraviolet spectroscopy and chemical extraction to the problem and found that the genes are made up of nucleoproteins. The chromosome is now known t o possess a definite nucleoprotein structure, the activity of which determines the course of development: Each species has a characteristic gene configuration. Imitation of genic effects can be produced by external agentsfor example, there is a lack of metamorphosis in tadpoles whioh
Molds of potential value in the production of antibiotics are studied under high-powered microscope 591
Biochemist weighs A-fricnn strophanthus weds hefore determining their steroid content
are fed diets deficient in iodine. Red eye pigmerits can be produced in insects by administering kynurenine, which is formed on1 the dietary esseiitial amino acid, tryptophan. Kynurcriiur now known to be the necessary component of the Drosophila V + gene hormone. In the biochemistry of the genes, v,-e can estimate the effect of a t least one biochemical substance on growth, normal and abnormal. Moreover, there is some indication that a study of gene stiniulators, retarders, or imit&ors may lead to the differentiation of cancer t k u e from noncaiiwr tissue, The complexity of the field covereci 1,y the Division of Biological Chemistry is well illustrated by the program of last year’s 118t,1i national meeting of the AMERICANCHEMICAL SOCIETYat, Chicago, Ill. Some 160 papers were presented, on fats, tracer elrments, enzymes, hormones, amino acids, steroids, tumors, cancer, antibodies, t80xins, antibiotics, riucleic acids and derivatives, microbiological assays, and chromatography. I n addit,ion, there were symposia on steroids and ACTH. The program covered biochemistry, health, disease, and public welfare-a multifaceted exposition of the applications of chemistry and physics to living processes. EARLY CONTRIBUTORS
Researcher at National Institutes of Health prepares crystalline residues of sarmmtosis glycosides
A f Los A lamos Scientijk Laboratory, samples containing radioncfive carhort are used in tracpr research
The tremendous growth of biochemistry in many fields I I L L L ~ C ~ it difficult to name originators or leaders. However, sonic ~ n ~ n fion should be made of a few early contributors. Russell H. Chittenden, who conducted the first cour3c in physiological chemistry in America, trained a number of rehcwrc,h workers and teachers in the field. By studying how the growth curves of young rats are influenced by diet, amino acids, and vitamins, T. B. Osborne and Lafayette B. Mendel added niuch to our knowledge of what coa~titiitesan adequate diet. Jjlnicr V. RIcCollum did outstanding n o i k in the vitamin field : i i i t f iii general nutrition. Alfred F. Hess conducted extensive investigations into i r ~ l a r iit l ~ wurvy and suggested sunlight a b a cure of rickets. H w r j S1wiihock found that irradiation M ith ultraviolet rays caused iriac%ivct vegetable oils t o acquirv antirachitic potency. Herbert, 11 Evans discovered the fertility vitamin which B Sure 1al)t~led vitamin E. William C. Roqe, by cmphasizing the classific~atlon of amino acids into those required in the diet and those which ale nonessential, added much to our understanding of nutrition Otto Folin and Stanley K.nenedict were leaders in developing new methods for rapid analysis of important biological conitituJohn ents, such as creatine, creatinine, and uric acid did outstanding work on adienaline and insulin. W. H. became noted for his study of blood coagulation. Trrat €3 Johnson mas a pioneer in the synthesis of compounds important in plant and animal metabolism. E. C. Kendall, a 1950 Nobel laureate, won acclaim for his woili on thyroxin and steroids. Phoebus -4. Levene was a master mind in elucidating the stiuctural formulas of nucleic acids. H. B. Lewis, 11 X. Sullivan, Erwin Brand, J. A. Stekol, and \’incent duvigneaud added mucsh new kno-rledge concerning the role of sulfur compounds in health aiid disease. H. B. Viclcery studied plant iind animal proteins. Robeit It. Williams et al. synthesized vitamin B1 or thiamine. H . ,I Rrilliams isolated pantothenic acid 13. H. Mitchell investigated the biological value of pioteins. H. D. Dakin added considrrably to our knowledge of chemical reactions in intermediar) metabolism and oxidation-reduction. Donald D. Van Slyke developed procedures of great value to biochemists, especially those engaged in the study of blood gases, acid-base balance, and microanalysis. Lawrence J. Henderson was a noted applier of physical chemistry to biological problems, particularly problerrii relating to blood. P. B. Hawk did excellent work on digestiori and is eqpecially noted for his textbook, “Practical Physiological
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Wyckoff in the application of the electron microscope; R. J. Chemistry,” which has gone through many editions and revisions Block in amino acid composition of food; and B. C. Knight, J. L. and is still widely used. I n 1932, C. G. King in the United Stokes, V. R. Potter, and D. W. Wooley in biological antagonism States and A. Szent-Gyorgyi abroad, independently and almost and antimetabolites. simultaneously described the preparation of crystalline One of the striking features of biochemical investigation in the vitamin C. United States has been the cooperative effort among the several Carl P. Sherwin was a pioneer in work on detoxication reacrelated fields of chemistry, physiology, nutrition, bacteriology, tions in the body. Ross H. Gortner was noted for his work on and medicine. This cooperation has been especially noted in the colloids, proteins, and the sulfur compounds in proteins. Walter investigations of vitamins and antibiotics-their isolation, idenR. Bloor became an expert in the field of lipoid chemistry. Jesse tification of structure, and physiological action. Jointly, organic F. McClenden did much original work on the effect of iodine in chemists, biochemishs, and medical specialists have diligently treating goiter. Henry C. Sherman, a highly productive worker screened innumerable compounds of possible use in offsetting or in the field of nutrition, emphasized the importance of mineral relieving malaria, tuberculosis, arthritis, cancer, and various elements in nutrition and the relation of nutrition to health and allergies. I n this cooperative work, a number of manufacturing lonnevitv. W. M. Clark studied the determination of hydrogen pharmaceutical firms have ions, as well as the reversible played and are continuing t o oxidation-reduction of orOfficers of the Division of Biological Chemistry, play an outstanding role. ganic compounds of impor1914-1951 For publication of findtance in biochemistry. Conrad ings, the biochemist in the A . Elvehjem won praise not Secretary Chairman Year United States has been well only for his investigation of I. K. Phelps 1914-17 Carl L. Alsberg taken care of b y textbooks, nicotinic acid as a cure for I. K. Phelps W. J. N. Osterhaut 1918 review journals, and current black-tongue but also for his R. A. Gortner Isaac K . Phelps 1919 periodicals. The Journal of excellent work on the relation A. W. Dox R. A. Gortner 1920 Biological Chemistry has long of various vitamins to nutriH. B. Lewis A. W. Dox 1921 enjoyed a high place in the tion. George Wald and Selig J. S. Hughes H. B. Lewis 1922 world biochemistry. LikeHecht added to our knowlW. T. Bovie 1922-23 J. S. Hughes wise, the newer journal, edge of visual purple. Many R. Adams Dutcher W. T. Bovie 1923-24 Archives of Biochemistry, is others could be included R. J. Anderson It. Adams Dutcher 1924-25 well considered. The A n n u a l among America’s most outJ. J. Willaman R. J. Anderson 1925-26 Review of Biochemistry ably standing biochemists. Paul E. Howe John R. RiIurlin 1926-27 covers c u r r e n t t o p i c s . M. X. Sullivan Paul E. Howe 1927-28 Through its publications, RECENT INVESTIGATIONS W. R. Bloor 1928-29 M. X. Sullivan the AMERICAN CHEMICAL When attention is given t o D. Breese Jones SOCIETY has brought together recent work in biological Icie G. Macy 1929-30 D. Breese Jones contributions from manydivichemistry in the United 1,. A. Maynard Icie G. Macy 1930-31 sions of chemistry. Through States, say within the past J. B. Brown 1931-32 L. A. Maynard Chemical Abstracts, the world 10 or 15 years, a bewildering Robert C. Lewis 1932-33 J. B. Brown literature is reviewed. With array of worth-while achieveA. W. Rowe 1933-34 Robert C. Lewis its monographs, the AMERIments is found. Progress has R. E. Remington CAN CHEMICAL SOCIETYhas been so rapid, the fields of C. G. King Roe E. Remington 1934-35 done a great service to the attack so widened, and the C. A. Elvehjem C. G. King 1935-36 wide field of chemistry, parapproach so ingenious, that W. C. Russell C. A. Elvehjem 1936-37 ticularly biological chemistry. it is difficult and, in fact, preJ. J. Pfiffner Walter C. Russell 1937-38 Of some 100 monographs mature to select the most G. 0. Burr Joseph J. Pfiffner 1938-39 published b y the Society up important investigators in Herbert 0. Calvery G. 0. Burr 1939-40 to 1940, 20 have dealt with the various lines of endeavor. Erwin Brand Herbert 0. Calvery 1940-41 biological chemistry. New fields have been deErwin Brand B. H. Nicolet 1941-42 Within a short period, some veloped and old fields markErwin Brand H. A. Shonle 1942-43 nine scientists in the United edly advanced-for exErwin Brand Elmer M. Nelson 1943-44 States have been Nobel Prize ample, microbiological asErwin Brand Arthur Knudson 1944-45 winners in chemistry and resay, chromatography, chemoErwin Brand Arthur Knudson 1945-46 lated fields. Of these, seven therapeutics, antibiotics, John T. Edsall Erwin Brand 1946-47 worked in biochemistry: immunochemistry, and the John T. Edsall Erwin Brand 1947-48 Doisy, vitamin K ; Sumnw hiochemistry of cancer. Paul W. Preisler John T. Edsall 1948-49 and Northrop, enzymes; While a host of productive Paul W. Preisler M. A. Lauffer 1949-50 Gerty and Carl Cori, carboworkers must be left unmenPaul W. Preisler John T. Edsall 1950-51 hydrates; Stanley, viruses; tioned in this brief history, Kendall, steroids. This outnotice should be taken of cerstanding record underscores the statement made by Treat B. tain men whose publications within recent years have been signifiJohnson in 1926 that in no country is more progress being made in cant--JesseP. Greensteinand Charles Hugginsin the biochemistry this new field of chemical science-biochemistry-than in America of cancer; S. A. Waksman, 0. Wintersteiner, H. E. Carter, V. duVigneaud, and R. Dubos in the antibiotic field; Michael HeidelLITERATURE CITED berger and K. Landsteiner in immunochemistry; A. S. Keston, S. Udenfriend, R. K Cannan, S. Moore, W. H. Stein, E. Vischer, (1) Browne, C.A.,J. Am. Chem. Soc., 48,No.8a (1926). (2) Chittenden, R. H., “Development of Physiological Chemistry in and E. Chargaff in chromatography; Esmond E. Snell and the United States,” A.C.S. Monograph 54, New York, ReinW. H. Peterson in microbiological methods for the assay of vitahold Publishing Corp., 1930. mins and amino acids; the Coris in sugar catabolism and anabo(3) Dobzhansky, Theodosius, Sci. American, 183, 55 (1950). lism; L. C. Craig in countercurrent distribution work; R. W. G. (4) Meyerhof, Otto, Ibid., 183, 62 (1950). I
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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
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