34 BIOGRAPHICAL MEMOIRS supplied by muscle infusion and yeast extract. The character of these reactions is determined by the presence or absence of molecular oxygen. In the presence of molecular oxygen, active extracts were shown to exhibit the following activities: consumption of molecular oxygen, formation of peroxide, oxidation of hemoglobin, and oxida- tion and destruction of the hemolysin and intracellular enzymes contained in pneumococcus extracts. All of these oxidations are ex- amples of "oxygen activation," whereby substances themselves not reactive with molecular oxygen are easily oxidized by agents formed during the oxidation of other substances. Analysis of these processes shows that the active systems consist of two components, one of which is thermolabile, the other thermo-stable. By themselves the thermo-stable substances react slowly with molecular oxygen to form oxidizing agents, and in the absence of molecular oxygen they establish conditions under which methemoglobin and other sub- stances are slowly reduced. In the presence of the thermolabile component, the reactions of oxidation and reduction are markedly ac- celerated. This latter component is wholly nonreactive with molecu- lar oxygen, possesses no reducing power, and seems to be catalytic in nature. When present together, these substances constitute systems responsible for many of the biological oxidations and reductions of the living cell. Avery in collaboration with G. E. Cullen made an interesting study of the intracellular enzymes of pneumococcus and, as a result, suggested their relationship to the metabolic activity of the cell. The demonstration of the intracellular agents was affected by breaking down the cell structure by suitable means and making extracts which were tested for enzymatic activity. In this way, active cell-free agents were obtained which hydrolyzed intact protein to some extent and which hydrolyzed peptones with striking avidity. An active esterase was also isolated as were such carbohydrate-splitting enzymes as in- vertase, amylase, and inulinase. On the other hand, fermentation of dextrose could not be demonstrated. These studies indicated that the enzymes described were not secretory products of the pneumococcus OSWALD THEODORE AVERY 35 but were of the nature of endo-enzymes, since their activity could be demonstrated ody when cell disintegration had occurred. At the time when Avery joined the staff of the Hospital of the Rockefeller Institute, the study of the pneumococcus and its relation- ship to lobar pneumonia had been in progress for about three years. As a result of this study, pneumococci had been separated by means k of immunological reactions into two different groups by Dochez and Gillespie. The first group consisted of Types I, II, and III, which could be sharply differentiated from one another by serological tests and were found only in association with severe examples of lobar pneumonia or in the mouths of individuals in close contact with such cases of pneumonia. The other group consisted of strains as- sociated with lobar pneumonia in a much smaller percentage of in- stances, and was of greater serological diversity. These latter strains resembled the varying types of pneumococcus found in the mouths :`, of healthy normal individuals. On his arrival, Avery joined in the study of the immunological classification of pneumococci and added to this classification several new serological types. As the study passed to other hands, many new immunological types were discovered. On the whole, the original Types I, II, and III remained fairly constant in from 60 to 80 percent of cases as the causative agents of the severe and highly fatal instances of lobar pneumonia. The results of these studies brought about a more exact knowledge of the character of pneumococcus infection of the lung, and shed a considerable amount of new light on the etiology and epidemiology of lobar pneumonia. In 1917 Dochez and Avery reported the elaboration of a specific soluble substance by the pneumococcus during its growth in culture medium. This substance was identical immunologically with the type of pneumococcus growing in the culture and was present in large amounts .at a time when little or no cell disintegration had taken place. The substance consequently did not represent dead dissolved bacterial protein, but was due to the elaboration and passage into solution of a substance which was the product of the life activity of the pneumococcus cell. That it was not an intracellular substance 36 BIOGRAPHICAL MEMOIRS liberated at the death and disintegration of the pneumococcus was proven by the fact that it was already present in considerable quan- tities at a time when no intracellular hemolysin was present in the culture medium. The intracellular hemolysin is liberated only on the death and disintegration of the cell, and the curve of hemolysin did not begin to rise until a time when the curve of the soluble substance had almost attained its maximum elevation. The formation of a soluble substance by the pneumococcus on growth in vitro suggested the probability that an analogous sub- stance would be formed on growth of the organism in the animal body, and because of the readiness with which the substance passed into solution it was expected that there would be no difficulty in demonstrating it in the body fluids of animals experimentally in- fected with pneumococcus and in those of human beings suffering from lobar pneumonia. This was found to be the case, since a spe- cific precipitin reaction with antipneumococcus serum correspond- ing to the type of organism with which the animal or human being was infected was easily demonstrated in the blood serum and urine during the period of infection. The discovery of this substance was of great importance to Avery's subsequent study of the pneumococcus,; since it served as the point of departure for much of his succeeding' research. From 1922 onward, Avery, Heidelberger, and their associates un- dertook a chemical study of the soluble specific substances, which Avery believed were an important key to the whole subject of the immunological specificity of bacteria. Papers were published show- ing that the soluble specific substances of the pneumococcus were polysaccharides, the first instance in which carbohydrates were shown to be involved in immune reactions. The soluble substances of Type II and Type III pneumococci were found to be nitrogen-free carbo- hydrates, the former made up mainly of glucose, and the latter com- posed of aldobionic acid units. The Type I polysaccharide was nitro- gen-containing, and made up in part of galactouronic acid. Differences in bacterial specificity were related by Avery and 0 OSWALD THEODORE AVERY . 37 Heidelberger to characteristic chemical differences in the substances responsible; where these substances were similar, cross-reactivities were found to occur, and accounted chemically for the observed spec- ificities. A whole new field of bacteriology, immunology, and chemistry was opened up. Many puzzling and confused observations in bacteriology and immunology were thus clarified and systematized on a rational chemical basis. At least a part of the virulence, specific- ity, and `behavior of many important bacteria is referable to a specific polysaccharide and in the encapsulated microorganism this is the major factor. Here, then, is one of the principal foundation stones of the science of immunochemistry, which is rapidly including an ever-widening study of artificial and natural antigens. Meanwhile, in the hands of Avery and his co-workers, knowledge of the specific characters of the pneumococci and the manner in which these are acquired had been moving to a new pinnacle of achievement. The culmination of this knowledge and of the studies conducted by Avery and his co-workers, Dawson, Alloway, MacLeod, McCarty, Taylor, and Hotchkiss, came with the announcement, in 1944, that the fundamental constituent of the transforming agent of pneumococcus Type III is a polymerized desoxyribonucleic acid. That the transformation of one type of pneumococcus into a pneu- mococcus of another type could occur in vivo was first demonstrated by Griffith in Igag. Studies on the mechanism of experimental trans- formation of pneumococcal types were carried out in Avery's labora- tory from 1928 to 1948. The transforming substance was extracted from heat-killed pneu- mococci or from living cells caused to undergo lysis. Sodium citrate, which inhibits the inactivating effect of pneumococcal desoxyribonu- clease, was used in the lysing process in the later procedures. After deproteinization, the desoxyribonucleic acid was further purified, so that an exceedingly minute quantity, 0.0015 microgram per milliliter, was capable in vitro of inducing transformation of susceptible cells under proper cultural conditions. Evidence that the transforming agent is a nucleic acid of the desoxyribose type was obtained by . 38 BIOGRAPHICAL MEMOIRS chemical, enzymatic, serologic, and physico-chemical studies of highly purified material. Elementary analysis showed that the ma- terial closely resembles authentic preparations of desoxyribonucleic acid of animal origin. Serological procedures with anti-pneumococcal sera of appropriate type failed to reveal the presence of capsular or somatic polysaccharides or of pneumococcus protein in the trans- forming material, each of which would easily have been demon- strated by such tests. Amino acids were obtained on hydrolysis in so small an amount that not more than 0.2 percent of protein could be present. Later studies showed that glycine from the degradation of adenine was ap- parently the only amino acid present in the hydrolysate, so that the possibility that a specific protein or nucleoprotein, rather than the nucleic acid itself, was responsible for the transforming activity seemed to have been excluded decisively. Highly purified preparations of the transforming agent obtained from pneumococcus Type III made possible for the first time the in- duction of a predictable and permanent alteration in a heritable character of the living cell by means of a chemically defined substance of known nature. In other words, a specific mutation was induced as a result of specific treatment, an achievement which had long i eluded biologists. The broad implications of the discovery of the na-. ture of the transforming agent became apparent when it was demon- strated in Avery's laboratory that desoxyribonucleic acids, separated from a number of other types of pneumococci, possess predictable transforming activity relative to a specific cell character. Confirma- tory evidence supporting Avery's interpretation of the transforma- tion phenomenon was later obtained in other laboratories with both pneumococcus and other microorganisms. As a result of these studies of Avery and his associates, it became apparent that certain polymerized desoxyribonucleic acids are con- cerned with the heredity of microbial cells in much the same fashion that genes are concerned with the hereditary characteristics of higher organisms. OSWALD THEODORE AVERY 39 The impact of these fin&rgs upon prevailing concepts of investi- gators in cytology, genetics, and virology, already aware that desoxy- ribonucleic acid is a prominent constituent of nuclei, chromosomes, and viruses, was of great importance. It was now learned that this constituent is the one functionally operative in transmitting the manifold biologic capacities and potentialities of the germ plasm. This, in turn, indicated to biochemists that nucleic acids are capable of innumerable variations in composition and structure. Both of these concepts have received considerable support, and it has become increasingly evident that they play an important part in the orient- ing of investigations in the several-fields concerned with cellular de- velopment and differentiation. At the time the above investigation was being presented, from its beginning to its successful conclusion in 1948, Avery and certain of his associates engaged in a number of collateral studies related to the immunological significance of carbohydrates, both those of bacterial origin and certain more common sugars. As a result of these studies an antigenic relationship was shown to exist between the polysac- charides and pneumococcus and those of certain types of Bacillus Friedlander and of a number of plant gums, such as gum acacia. Following this, a study of the specificity of certain azo-protein anti- gens containing simple saccharides of known chemical constitution was-undertaken with W. F. Goebel. This study showed unequivo- cally that the specificity of carbohydrates was determined by their chemical constitution and that differences in structure, no matter how slight, were invariably reflected in the specificity of the anti- bodies which such antigens evoked. As an example, the specific poly- saccharide of Pneumococcus Type T is characterized by the presence of a highly labile acetyl group. Gentle removal of this group de- prives this polysaccharide of its antigenicity in certain animals and alters its over-all serological specificity as well. A species-specific carbohydrate distinct from the capsular polysac- charide was isolated from the somatic component of pneumococci. This substance was designated as Fraction C. It subsequently became 40 BIOGRAPHICAL of considerable interest, since it gave MEMOIRS rise to a precipitating antibody in the serum of patients suffering from pneumonia, which was pres- ent only during the acute phase of the disease and disappeared dur- ing convalescence. The antibody is not specific for pneumonia, but also occurs during the acute phase of a number of infections, such as rheumatic fever, and in conditions associated with tissue degenera- tion. Its presence or absence is now regularly used as a measure of the activity of the clinical condition under study. During this time Avery in collaboration with Rent Dubos investi- gated the action of a bacterial enzyme which decomposed the poly- saccharide of Pneumococcus Type III, both in vitro and in vivo. This enzyme, when injected in conjunction with virulent Type III pneumococcus, was capable of protecting mice, rabbits, and monkeys against experimental infection because of its capacity of stripping the virulent cell of its protective capsular coat. This constituted one of the very early demonstrations of antibiotic action against patho- genic microorganisms, a procedure which has since become of great i importance in the cure of numerous infectious diseases. Avery also participated with Dochez and Lancefield in an im- munological classification and antigenic analysis of the hemolytic streptococcus. This study proved that this organism is not a unit type, as was previously supposed, but consists of a number of types which can be definitely identified serologically. Subsequent development and employment of the techniques used resulted in the establish- ment of the hemolytic streptococcus as the causative agent of scarlet fever, acute rheumatic fever, and hemorrhagic nephritis, all of which diseases may now be brought within the range of prevention or cure by antibiotic agents effective against the hemolytic streptococcus. Avery, by his studies of the chemical basis for the differences be- tween the several types of pneumococcus and the importance of car- bohydrates in determining the antigenic specificity of bacterial and synthetic antigens, became one of the founders of the modern science of immunochemistry, a science which has rapidly come to include an ever-widening range of studies of artificial and natural antigens. OSWALD During both the First and THEODORE AVERY .4I the Second World Wars, Avery placed his scientific knowledge and skill at the disposal of the United States Government, serving on various committees concerned with the con- trol of a number of important infectious diseases which are prevalent among troops under conditions of warfare. During his active career he received a number of honorary degrees: Sc.D., Colgate University, 1921; L.L.D., McGill University, 1935: Sc.D., New York University, 1947; and Sc.D., Rutgers University 1953. In addition, he was awarded a number of other honors and prizes, among them the Paul Ehrlich Gold Medal and the Copley Medal of the Royal Society of London. He was elected to the National Academy of Sciences in 1933 and was also a foreign member of the Royal Society of London. Dr. Avery was a true scientist with an insatiable curiosity and a powerful and unremitting urge to discover the innermost mecha- nisms of the biological facts that came under his observation. His ap- proach to the solution of a problem was characterized by a logical simplicity of thought and a perfection of technical procedure, com- bined with a complete objectivity that guaranteed the soundness of his deductions. Most of Avery's associations were with his colleagues, by whom he was greatly revered and who have preserved for him a timeless affection. He was a truly lovable person, humble, disinter- ested, and generous. The inspiring and friendly quality of his leader- ship is conspicuously represented by his many former associates who ,.. . . istmgulshed :, so that his positions in light still bu medicine in rns in many the plan United States :es of learning r Occupy d elsewhere research. 42 BIOGRAPHICAL MEMOIRS KEY TO ABBREVIATIONS Ann. Int. Med.= Annals of Internal Medicine Arch. Int. Med.= Archives of Internal Medicine Arch. Pediat. = Archives of Pediatrics Centr. Bakt.=Zentralblat fiir Bakteriologie J.A.M.A.= Journal of the American Medical Association J. Exp. Med. = Journal of Experimental Medicine J. Infect. Dis.= Journal of Infectious Diseases J. Med. Res.= Journal of Medical Research Prnc Snc. Exp. Biol. Med.=Proceedings of the Society for Experimental Bi- ology and Medicine Trans. Assn. Am. Phys.=Transactions of the Association of American Physi- cians BIBLIOGRAPHY I `909 -. With B. White. The Treponema Pallidum; Observations on its Occur- rence and Demonstration in Syphilitic Lesions. Arch. Int. Med., 3:411, 1910 With N. B. Potter. Opsonins and Vaccine Therapy. (In: Hare, Modern Treatment, Philadelphia and New York, I :515.) With B. White. Observations on Certain Lactic Acid Bacteria of the So-called Bulgaricus Type. Centr. Bakt., Abt. II, 25~61. With L. C. Ager. A Case of Influenza Meningitis. Arch. Pediat., 32:284. With B. White. Concerning the Bacteremic Theory of Tuberculosis. J. Med. Res., 23:95. 1912 With 13. White. The A c ion of Certain Products Obtained from the Tu- t bercle Bacillus. A. Cleavage Products of Tuberculo-protein Obtained by the Method of Vaughan. Communication I. The Poisonous Substance. J, Med. Res., 26:317. 19'3 With H. W. Lyall. Concerning Secondary Infection in Pulmonary Tuber- culosis. J. Med. Res., 28:111. With B. White. Some Immunity Reactions of Edestin. III. The Biological Reactions of the Vegetable Proteins. J, Infect. Dis., 13:103. OSWAZD THEODORE AVERY 43 `9'4 With C. E. North and B. White. A Septic Sore Throat Epidemic in Cortland and Homer, New York, J. Infect. Dis., 14:124. 19'5 With A. R. Dochez. V arte tes of .Pneumococcus and Their Relation to * t' Lobar Pneumonia. J. Exp. Med., 21 :I 14. The Distribution of the Immune Bodies Occurring in Anti-pneumococcus Serum. J. Exp. Med., 21:111. With A. R. Dochez. The ¤ce of Carriers of Disease-producing Types of Pneumococcus. J. EXP. Med.. 22:107. A Further Study on the Biologic Classifications of Pneumococci. J. Exp. Med., 22 $04. 1916 With A. R. Dochez. Antiblastic Immunity. J. Exp. Med., 23:61. 1917 With H. T. Chickering, R. Cole, and A. R. Dochez. Acute Lobar Pneu- monia: Prevention and Serum Treatment. Monographs of the Rocke- feller Institute for Medical Research, No. 7. With A. R. Dochez. Soluble Substance of Pneumococcus Origin in the Blood and Urine During Lobar Pneumonia. Proc. Sot. Exp. Biol. Med., 14:126. With A. R. Dochez. The El b a ora ton of Specific Soluble Substance by t' Pneumococcus During Growth. J. Exp. Med., 26:477; Trans. Assn. Am. - Phys.; 32:281. 1918 Determination of Types of Pneumococcus in Lobar Pneumonia :,A Rapid Cultural Method. J.A.M.A., 70:17. _--. - ." _, With K. G. Dernby. The Optimum Hydrogen Ion Concentration for the ./ i Growth of Pneumococcus. J. Exp. Med., 28:345. A Selective Medium for B. Influenzae. Oleate-hemoglobin Agar. J.A.M.A., il;, 7Iz2050. ,:: - :. `9'9 +With G. E. Cullen. The Use of the Final Hydromen Tnn rnnra.+-n+:-- :- `E ""LICCIIL, I * Differentiation of Streptococcus Haemolyticu, VL I &",, E Types. J. Exp. Med., 2g:q. `man and dLI"II 11, Bovine 44 BIOGRAPHICAL MEMOIRS With A. R. Dochez and R. C. Lancefield. Studies on the Biology of Streptococcus. I. Antigenic Relationship's Between Strains of Strepto- coccus Haemolyticus. J. Exp. Med., 30:x79. 1920 With G. E. Cullen. Studies on the Enzymes of Pneumococcus. I. Proteo- lytic Enzymes. J. Exp. Med., 32:547. With G. E. Cullen. Studies on the Enzymes of Pneumococcus. II. Lipo- ( lytic Enzymes: Esterase. J, Exp. Med., 32:571. With G. E. Cullen. Studies on the Enzymes of Pneumococcus. III. Carbo- hydrate-splitting Enzymes: Invertase, Amylase, and Inulase. J. Exp. Med., 32 ~583. 1921 With T. Thjotta. Studies on Bacterial Nutrition. II. Growth Accessory Substances in the Cultivation of Hemophilic Bacilli. J. Exp. Med., 34:97. With T. Thjotta. Studies on Bacterial Nutrition. III..Pla.nt Tissue "S a Source of Growth Accessory Substances in the Cultivation of Bacillus Influenzae. J. Exp. Med., 34:455. With T. Thjotta. Growth Accessory Substances in the Nutrition of Bac- teria. Procl Sot. Exp. Biol. Med., x8:197. With H. J. Morgan. The Effect of the Accessory Substances of Plant Tis- sue Upon Growth of Bacteria. Proc. Sot. Exp. Biol. Med., 19:113. `923 . With M. Heidelberger. Soluble Specific Substance of Pneumococcus. J. Exp. Med., 38:73. With M. Heidelberger. Immunological Relationship of Cell Constitu- ents of Pneumococcus. J. Exp. Med., 38 :81. With M. Heidelberger. The Specific Soluble Substance of Pneumococcus. Proc. Sot. Exp. Biol. Med., 20:&. With M. Heidelberger. Immunological Relationships of Cell Constitu- ents of Pneumococcus. Proc. Sot. Exp. Biol. Med., zo:435. With G. E. Cullen. Studies on the Enzymes of Pneumococcus. IV. Bac- teriolytic Enzyme. J. Exp. Med., 38:199. With H. J. Morgan. Studies on Bacterial Nutrition. IV. Effect of Plant Tissue Upon Growth of Pneumococcus and Streptococcus. J. Exp. Med., 38 ~207. . OSWALD THEODORE AVERY 45 1924 With H. J. Morgan. The Occurrence of Peroxide in. Cultures of Pneu- mococcus. J. Exp. Med., 3g:275. With H. J. Morgan. Studies on Bacterial Nutrition. V. The Effect of Plant Tissue Upon Growth of Anaerobic Bacilli. J. Exp. Med., 39:28g. With H. J. Morgan. Growth-inhibitory Substance in Dneumococcus Cul- tures. J. Exp. Med., 39:335. With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. I. Production of Peroxide by Anaerobic Cultures of Pneumococcus on Exposure to Air Under Conditions Not Permitting Active Growth. J. Exp. Med., 3g:347. With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. II. The Production of Peroxide by Sterile Extracts of Pneumococcus. J. Exp. Med., 3g:357. With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. III. Reduction of Methylene Blue by Sterile Extracts of Pneumococcus. J. Exp. Med., 39:543. With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. IV. Oxidation of Hemotoxin in Sterile Extracts of Pneumococcus. J. Exp. Med, 39:745. With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. V. The Destruction of Oxyhemoglobin by Sterile Extracts of Pneumo- coccus. J. Exp. Med., 3g ~757. With M. Heidelberger. The Soluble Specific Substance of Pneumococcus. J. Exp. Med., 40:301. With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. ,VI. The Oxidation of Enzymes in Sterile Extracts of Pneumococcus. J. Exp. Med., 40:405. With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. VII. Enzyme Activity of Sterile Filtrates of Aerobic and Anaerobic Cultures of Pneumococcus. J. Exp. Med., 40:423. 1925 With J. M. Neill. Studies on Oxidation and Reduction by Pneumococcus. VIII. Nature of Oxidation-reduction Systems in Sterile Pneumococcus Extracts. J. Exp. Med., 41:285. With H. J. Morgan. Immunological Reactions of Isolated Carbohydrate and Protein of Pneumococcus. J. Exp. Med., 42:347. 46 BIOGRAPHICAL MEMOIRS With J. M. Neill. The Antigenic Properties of Solutions of Pneumococcus. J. Exp. Med., 42:355. With M. Heidelberger. Immunological Relationships of Cell Constituents of Pneumococcus, J. Exp. Med., 42367. With M. Heidelberger and W. F. Goebel. The Soluble Specific Substance ( of a Strain of Friedlander Bacillus. Proc. Sot. Exp. Biol. Med., 23:`. With M. Heidelberger and W. F, Goebel. Immunological Behavior of the "E" Strain of Friedlander Bacillus and Its Soluble Specific Substance. Proc. Sot. Exp. Biol. Med., 23:~. With M. Heidelberger and W. F. Goebel. The Soluble Specific Substance of a Strain of Friedlander's Bacillus. J. Exp. Med., 42:701. With M. Heidelberger and W. F. Goebel. The Soluble Specific Substance of Friedlander's Bacillus. Chemical and Immunological Relationships of Pneumococcus Type II and a Strain of Friedlander's Bacillus. J. Exp. Med., 42:709. With M. Heidelberger and W. G. Goebel. The Soluble Specific Substance of Pneumococcus. J. Exp. Med., 42:727. 1927 With W. F. Goebel. The Soluble Substance of Friedlander's Bacillus. III. On the Isolation and Properties of the Specific Carbohydrates from Types A and C Friedlander Bacillus. J. Exp. Med., 46:6or. `929 With W. S. Tillett. Anaphylaxis with the Type-specific Carbohydrates of Pneumococcus. J. Exp. Med., 49:251. With W. F. Goebel. A Study of Pneumococcus Autolysis. J. Exp. Med., 49 :267. With M. Heidelberger and W. F. Goebel. A "Soluble Specific Substance" Derived from Gum Arabic. J. Exp. Med., 4g:847. With W. F. Goebel. Chemo-immunological Studies on Conjugated Carbo- hydrate-proteins. I. The Synthesis of p-aminophenol B-glucoside, p-ami- nophenol B-galactoside, and Their Coupling with Serum Globulin. J. Exp. Med., 50:521. With W. F. Goebel. Chemo-immunological Studies on Conjugated Carbo- hvdrate-oroteins. II. Immunological Specificity of Synthetic Sugar- --, --~ I protein Antigens. J. Exp. Med., 50:533. OSWALD THEODORE AVERY 47 With W. S. Tillett and W. F. Goebel. Chemo-immunological Studies on Conjugated Carbohydrate-proteins. III. Active and Passive Anaphylaxis with Synthetic Sugar-proteins. J. Exp. Med., 50:551. `930 With W. Tillett and W. F. Goebel. Chemical and Immunological Prop- erties of a Species-specific Carbohydrate of Pneumococci. J. Exp. Med., 52 :895. With R. Dubos. The Specific Action of a Bacterial Enzyme on Pneumo- cocci of Type III, Science, 72:151. `93' With R. Dubos. The Specific Action of a Bacterial Enzyme on Type III Pneumococci. Trans. Assn. Am. Phys., 46:216. With R. Dubos. Decomposition of the Capsular Polysaccharide of Pneu- mococcus Type III by a Bacterial Enzyme. J. Exp. Med., 54:51. With R. Dubos. The Protective Action of a Specific Enzyme Against Type III Pneumococcus Infection in Mice. J. Exp. Med., 54:73. With W. F. Goebel. Chemo-immunological Studies on Conjugated Car- bohydrate-proteins. IV. The Synthesis of the p-aminobenzyl Ether of the Soluble Specific Substance of Type II Pneumococcus and Its Cou- pling with Protein. J. Exp. Med., 54:431. With W. F. Goebel. Chemo-immunological Studies on Conjugated Car- bohydrate-proteins. V. The Immunological Specificity of an Antigen Prepared by Combining the Capsular Polysaccharide of Type II Pneu- mococcus with Foreign Protein. J. Exp. Med., 54:437. 1932 With W. F. Goebel and F. H. Babers. Ch emo-immunological Studies on Conjugated Carbohydrate-proteins. VI. The Synthesis of p-aminophenol a-glucoside and Its Coupling With Protein. J. Exp. Med., 55:761. With W. F. Goebel and F. H. Babers. Chemo-immunological Studies on Conjugated Carbohydrate-proteins. VII. Immunological Specificity of Antigens Prepared by Combining a- and b-glucosides of Glucose with Proteins. J. Exp. Med., 55:769. The Role of Specific Carbohydrates in Pneumococcus Infection and Im- munity. Ann. Int. Med., 6:1. . . 48 BIOGRAPHICAL MEMOIRS With K. Goodner and R. Dubos. The Action of a Specific Enzyme Upon the Dermal Infection of Rabbits with Type III Pneumococcus. J. Exp. Med., 55 :393. `933 Chemo-Immunologische Untersuchungen an Pneumokokken-Infektion und -1mmunitat. Naturwissenschaften, x:777. With W. F. Goebel. Chemo-immunological Studies on Soluble Specific Substance of Pneumococcus. I. The Isolation and Properties of Acetyl Polysaccharide of Pneumococcus Type I. J. Exp. Med., 58:731. 1934 With W. F. Goebel and F. H. Babers. Chemo-immunological Studies on Conjugated Carbohydrate Proteins. VIII. The Influence of the Acetyl Group on the Specificity of Hexoside-protein Antigens. J. Exp. Med., 6o:85. With W. E. Goebel and F. H. Babers. Chemo-immunological Studies on Conjugated Carbohydrate Proteins. IX. The Specificity of Antigens Prepared by Combining the p-aminophenol Glycosides of Disaccha- rides with Protein. J. Exp. Med., 60: With T. Francis, E. E. Terrell, and ii8 9. . Dubos. Experimental Type III Pneumococcus Pneumonia in Monkeys. II. Treatment with an Enzyme Which Decomposes the Specific Capsular Polysaccharide of Pneumo- coccus Type III. J. Exp. Med., 5g:641. `94' With T. J. Abernethy. The Occurrence During Acute Infections of a Pro- . tein Not Normally Present in the Blood. I. Distribution of the Re- 1 active Protein in Patients' Sera and the Effect of Calcium on the Floe- culation Reaction with C-polysaccharide of Pneumococcus. J. Exp. Med., i d; 73 :r73. $ With C. M. MacLeod. The Occurrence During Acute Infections of a Protein Not Normally Present in the Blood. II. Isolation and Properties ] B of the Reactive Protein. J. Exp. Med., 73:183. With C. M. MacLeod. The Occurrence During Acute Infections of a 1 Protein Not Normally Present in the Blood. III. Immunological Prop- 1 erties of the C-reactive Protein and its Differentiation from Normal Blood Proteins. J. Exp. Med., 73x91. I 1 1 OSWALD THEODORE AVERY 49 `944 With C. M. MacLeod and M. M c C arty. Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types. Induction of Transformation by a Desoxyribonucleic Acid Fraction Iso- lated from Pneumococcus Type III. J. Exp. Med., 7g:r37. I946 With M. McCarty. Studies on the Chemical Nature of the Substance In- ducing Transformation of Pneumococcal Types. II. Effect of Desoxy- ribonuclease on the Biological Activity of the Transforming Substance. J. Exp. Med., 83:89. With M. McCarty. Studies on the Chemical Nature of the Substance In- ducing Transformation of Pneumococcal Types. III. An Improved Method for the Isolation of the Transforming Substance and Its Ap- plication to Pneumococcus Types II, III, and VI. J. Exp. Med., 83:g7. With M. McCarty and H. E. Taylor. Biochemical Studies of Environ- tpental Factors Essential in :Transformation of Pneumococcal Types. Cold Spring Harbor Symposta on Quantitative Biology, II :177.