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RENE J ULES DUB OS February 20, 1901-February 20, 1982 BY JAMES G. HIRSCH AND CAROL L. MOBERG REN~ JULES DUBOS, microbiologist and humanist- philosopher, was professor emeritus at The Rockefeller University at the time of his death in New York City on his gist birthday, February 20, 1982. His name calls to mind a tall, vigorous, rosy-cheeke(1 man, with durable white wisps on a balding hea(l, intense blue eyes behind thick glass lenses, a shy yet broac! smile, and beautiful large hancis that enthu- siastically punctuated every sentence. He was a spellbinding speaker and a prolific author. His charming French accent and his perfect command of English made any contact with him memorable. Whether it was a private conversation or a public lecture, he always spoke with the knowledge of a scien- tist, the eloquence of a poet, and the wisdom of a philoso- pher. Rene was born in Saint-Brice-sous-Foret, France, on Feb- ruary 20, 1901, and grew up in Henonville, another small Ile-cle-France farming village north of Paris. His parents, Georges Andre Dubos and Adeline De Bloedt, ran a butcher shop in each of these villages. Rene attended a one-room school where discipline was strict and students taught one another. He was a husky boy, fascinated by sports, especially bicycle racing and tennis, but at age eight he suffered a severe 133

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134 BIOGRAPHICAL MEMOIRS attack of rheumatic fever that incapacitated him for more than a year and left him with ciamaged heart valves. Early in his youth he was also found to be severely near-sightecl, a condition that requires! thick corrective lenses. These afflic- tions instilled in him a fear of possible blindness and of a shortener! lifespan, a fear that he never shower! but that nonetheless caused him to live with special intensity and pur- pose. In place of typical childhood! activities, Rene cleveloped traits that would dominate the rest of his life. He walker! anc! explored the countryside, a pastime that helped him cultivate a meditative mood- what he caller! the beginning of his free- lance spirit. He also react avidly in history and literature, find- ing his earliest heroes in French translations of stories about Buffalo Bill anct Nick Carter. The family mover! to Paris when Rene was thirteen years old. Within months, his father was callect to WorIc! War I. Shortly after his return in HIS, he fell ill and in 1919, cried. The raising of three children (Rene, his brother Francis, and sister Madeleine) and the management of the family shop were left to his mother. Rene helpe(1 run the butcher shop while continuing his schooling at the College Chaptal. At fourteen, he read Hippolyte Taine's essay on La Fontaine and was introclucec! to the concept of the environment as a moIct- ing force on historical events, particularly on the human psyche. At age eighteen he applied to the Ecole cle Physique et Chimie, but another attack of rheumatic fever caused him to miss the entrance examination. After recovering he took the next test that came up, in economics, an(1 was pleasantly sur- prised that he die! well, ranking fourth out of 400. He was acimittec! to the Institut National Agronomique and excellect in all courses except microbiology" an intensely boring course, he later recalled, that dealt solely with taxonomy. He neither enjoyed nor excelled in chemistry and toIcl his

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RENE JULES DUBOS 135 mother that this was certainly the last time he would walk into a laboratory. In his third year he won a scholarship spon- sored by the government of Indochina for studies of agri- culture and technology in the Ecole d'Agriculture Coloniale in Paris with a required period of service in Southeast Asia, but was later disqualified because of his rheumatic heart ctis- ease. In 1922, Rene obtained a position in Rhine on the staff of the International Institute of Agriculture, a branch of the League of Nations. For two years, as associate editor of the International Review of the Science and Practice of Agriculture for the Bureau of Agricultural Intelligence anct Plant Diseases, he abstracted journal and agricultural reports from all over the world. He now spoke Italian and English as well as French and German. Rene recalled his clays in Rome as very pleasant. He was a handsome young man with a bushy head of hair who was particularly attracted to English girls, ostensibly to improve his language skills. At this time he was undecided about career goals, considering occupations as divergent as . . . Burma fist and soent~st. In the course of his translation duties Rene encountered an article that he considered the major influence in his life. While sitting in the Palatine Gardens on a warm May (lay, instead of reacting about fertilizers in a semipopular journal, he turned to an article by the famous Russian soil micro- biologist Serge Winogradsky, then at the Pasteur Institute in Paris. In it Winogradsky stated that microorganisms should be studied not in a pure laboratory culture but in their own environment in competition with other bacteria. He empha- sized interactions of organisms under natural conditions and the significance of the role played by the environment in these interactions. Rene said his scholarly life began with these ideas ideas he restated in many forms throughout his life. (Although the two men never met, Winogradsk.y pre-

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136 BIOGRAPHICAL MEMOIRS sensed Rene's paper, based on his Rutgers thesis research, at the Academie des Sciences in Paris in 1927.) This experience played a major role in his decision to become a bacteriologist. But Rene did not know how to begin until he met the American delegate to the International In- stitute of Agriculture, Asher Hobson, a professor of econom- ics from the University of Wisconsin. Hobson urged Dubos to emigrate to America and even offered to lend him money. Rene took a course in bacteriology at the University of Rome, earning extra money to pay for his passage to America by translating books on forestry and agriculture into French. In 1924, at a conference on soil science in Rome, Hobson intro- duced Dubos to Dr. Selman Waksman, who was then a distin- . guished bacteriologist at Rutgers University. Rene's duties as technical assistant during the Congress included showing Dr. and Mrs. Waksman around Rome. Fate intervened a few weeks later when Rene set sad! for America and found that the Waksmans were fellow passengers on the steamship, Ro- chambeau. They had plenty of time to talk during the cross- ing; Waksman was delighted to hear of Dubos's ambitions and, learning Rene had no definite plans, offered him a small fellowship as one of his graduate students at Rutgers. Rene arrived in America and went to New Brunswick with the Waksmans that same evening. Three years later he com- pleted his doctor of philosophy degree, doing thesis research on the decomposition of cellulose by soil bacteria. He cred- ited Waksman with helping him develop an ecological con- cept of microbiology through an understanding of the rela- tion between biochemical and biological processes. Dubos earned extra money working part time as an animal caretaker at nearby Johnson & Johnson, tutoring the research direc- tor's children, washing laboratory glassware on holidays, and translating papers on poultry pathology for a young pro- fessor.

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RE N E J u LE S D U B O S 137 It was just about this time that Rene, a bucicling scientist with an abstract humanist education, read Lewis Mumforct's Sticks anal Stones. Rene said this American author influenced his social philosophy by making him realize that institutions exist not to foster political or economic power, but to serve human needs and thereby broaden the quality of human life. Moreover, Mumforct wrote about subjects related to sciences and humanities in earthy terms that describec! sensory ex- periences of ciaily life. Mumford's writing had a lifelong effect on this impressionable young European trying to understand American ways and to express himself in English. Rene had no special plans after gracluation, except for wanting to move from the field of soil science to deal with more fundamental biochemical problems. His application for a National Research Council Fellowship was rejectee! because he was not a citizen. The secretary who sent the rejection letter penned a note at the bottom recommencing that he consult with a fellow Frenchman, Alexis Carrel, at The Rockefeller Institute in New York. This chance event led Rene to The Rockefeller, where he was clestined to spend some fifty years of his life. Carrel was kink] ant! considerate but had no special advice. He took him to lunch and there, whether by chance or prearrangement, Rene was seated next to Oswald Avery. Dubos ant! Avery liked each other imme- diately, spending not only the lunch hour but most of the afternoon discussing Rene's experiences with soil enrichment as a technique for recovering microbes that could do almost anything ant! Avery's preoccupation with the capsule of the pneumococcus and its role in virulence. Rene brashly stated that it should be easy to find an organism that couIcl make a capsule-ciestroying enzyme, a statement that impressed Avery. In the summer of 1927, without a job or definite plans, Rene was France's official delegate at the First International

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138 BIOGRAPHICAL MEMOIRS Congress of Soil Science in Washington, D.C. Along with 275 soil scientists from all over the world, he traveler! throughout the United States and Canada in a chartered train to visit agricultural experiment stations and to examine clifferent soil formations. He was offered at least two jobs that summer, one at the Experiment Station in Fargo, North Dakota, anc} the other at The Rockefeller with Averyat half the Fargo salary which he readily accepted. A series of acciclental events tract finally lecl him to a place where he could immerse himself in activities favorable to the clevelopment of his re- markable career. Dubos's laboratory career can be diviclect into three gen- eral phases. The microbiology period, from 1927 to 1944, was devoted to demonstrating that bacteria nourished in the proper environment can produce enzymes specific to those bacteria and to showing that bacteria have genetic mecha- nisms. During the tuberculosis and experimental pathology period from 1944 to 1960, certain products of bacteria were shown to stimulate immunity, ant] environmental factors were found to influence susceptibility to clisease. The envi- ronmental period, from 1961 to 1971, was (1ecticated to show- ing that various environmental stresses affect the develop- ment of the whole organism. At no time was there a gap or significant change in the direction of his career. The fourth ant! final phase of his life, from his official retirement in 1971 until his cleath in 1982, was spent writing and lecturing on environmental and social determinants of health anc! disease. As he evolved into an environmentalist, he appliecl his earlier concerns to broader fields. His interests progresses! from studies of pneumonia and tuberculosis to the whole pattern of disease ancl, finally, to the quality of human life on earth. The unifying thread in this seeming diversity was his perception that any living or-

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REN E J u LE S D U B O S 139 ganism, whether microbe, man, or society, can be unclerstooct only in the context of the entire web of relationships it forms with everything else. A brief review of his major accomplish- ments in each of these phases reveals his continuous search for those factors in health that he believer! are cleterminecT more by surroundings than by the mere presence or absence of microbes. The microbiology period began with Dubos working alone in a small laboratory on the sixth floor of The Rocke- feller Institute Hospital. Within three years, he succeeciect in fulfilling the promise he had made to Avery: He recovered a microorganism that clecomposed the capsule of Type TIT pneumococcus. He then proceedect to extract anct purify the enzyme responsible for this activity, and finally he clemon- strated that administration of the enzyme would protect rab- bits or monkeys against usually fatal experimental pneumo- coccal infection. These impressive laboratory findings were described in several papers between 1930 anct 1934. The en- zyme might well have been further purified anct then usect to treat certain cases of pneumococcal pneumonia in humans, but the sulfa drugs had just become available for the treat- ment of this clisease. The capsule-clestroying enzyme Did not achieve fame as a specific therapeutic agent, but the research on this material was nevertheless an auspicious beginning of Dubos's microbiological work. In his search for a capsule-destroying microbe, Rene used the soil enrichment technique ant! addect the capsular ma- terial to various soil samples. When he tract isolated a suitable organism and maintained it in pure culture in the laboratory, he made the arresting discovery that the organism producect the capsule-destroying enzyme only if the capsular material were included as the sole source of carbohydrate in the cul- ture medium. He called this phenomenon adaptive, or in-

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40 BIOGRAPHICAL MEMOIRS clucecI, enzyme formation, which demonstrates! that a cell has multiple potentialities that become manifest only when placed in an environment where it is compeller! to use them. Rene often referrer] to this discovery as the greatest in- tellectual satisfaction of his research career. The techniques in biochemistry ant! genetics to inquire further into this phe- nomenon were not yet available, but were later user! by his friends Jacques Monoc3, Francaois Jacob, and Andre Ewoff, who receiver! the Nobel Prize for their work on this topic. In the mid-1930s Rene ant! colleagues used the soil en- richment technique to isolate bacterial enzymes that cle- stroyed creatinine and enzymes that converted creatine into creatinine. These materials were used to develop methods for measuring creatinine in the blood and urine, which had not been possible up to that time. In 1937 anct 1938 he published papers on the recovery and partial purification of the enzyme that degrader! one type of nucleic acid, and he named the enzyme ribonuclease. He did no further work with the en- zyme, but it server! as the basis for research by a number of scientists at The Rockefeller. Moses Kunitz further purifier! ribonuclease and obtained crystals of this protein. Stanford Moore and William H. Stein used the highly purifier! ribo- nuclease as material for their work on amino acid analysis of proteins, and Bruce Merrifield used ribonuclease in his first synthesis of an enzyme discoveries for which these three men were awarded Nobel Prizes in chemistry. Dubos's best known and most remarkable achievement during his microbiology period was the discovery of grami- ciclin and tyrocidin the first antibiotics systematically culti- vated from bacteria and proclucecl commercially. Baser! on his several successes using soil as a source of special orga- nisms, he searched for a microbe that wouIct produce a sub- stance capable of destroying intact bacteria. His search cul- minatec! in the isolation of Bacillus breves, from which he

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RENE JULES DUBOS 141 extracted the active soluble principle he callect tyrothricin that contains two substances that attack gram-positive orga- nisms. Tyrocidin kills bacteria in vitro but not in viva ant! is toxic to animals; gramiciclin is active both in the test tube and in animals but is limited to external use (superficial wounds, bovine mastitis) because it causes hemolysis. Papers on these substances published between 1939 ant! 1941 established their structure, antibacterial activity, and clinical efficacy. In this way, Dubos provided methods through which other antibiotics came to be discovered. His work stimulated Howard Florey and Ernst Chain to look further into Alex- ander FIeming's penicillin, which was found in 1928 but nei- . ther purified nor obtained in large enough quantities for test- ing. It also stimulated Waksman, Rene's former teacher, to undertake a search that led to streptomycin. Fleming, Florey, Chain, ant! Waksman subsequently received Nobel Prizes for their discoveries. Dubos's antibiotics are not the ones widely used for the treatment of bacterial infections, yet he was a true pioneer in the clevelopment of antibiotics the most mo- mentous development in the history of meclical science. By 1941, when Rene was barely forty, the publicity sur- rounding his discovery of tyrothricin tract made him a famous man. In that year, he reacher! the highest rank, full member, at The Rockefeller Institute ant! was one of fifteen members elected to the National Academy of Sciences. He was not, however, carried away by the notion that antibiotics were wonder drugs that would eliminate all disease. In a 1942 ar- ticle in the Annual Review of Biochemistry, he prectictect that bacteria wouIct adapt themselves to these ctrugs and that new strains wouIcl become resistant. Having opened the pathway for the discovery of antibiotics, he no longer found it intel- lectually challenging nor was he interested in devoting his life to finding more of them. He felt this type of research was more suitable for pharmaceutical laboratories.

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142 BIOGRAPHICAL MEMOIRS The fifteen years of this microbiology period were, for the most part, happy and successful. In 1934 he married Marie-Louise Bonnet, a French teacher and pianist, and in 1938 he became an American citizen. He sufferer! a third episode of rheumatic fever, however, following a severe strep- tococcal infection. In 1940- under the stress of family prob- lems related to worIc! War IT his wife developed pulmonary tuberculosis, a reactivation of a childhood infection. Her con- dition grew progressively worse, and Rene, hoping that she would benefit from a change of environment, accepted a pro- fessorship at Harvard Medical School. But Marie-Louise diect in the spring of 1942, and Rene went to Boston suffering from the severe emotional shock of her death. As George Fabyan Professor of Comparative Pathology and Tropical Medicine at Harvard from 1942 to 1944, Rene had minimal teaching and administrative responsibilities and could concentrate on research. His letter of acceptance stated his wish to study the physiology and immunology of the tu- bercle bacillus and tuberculosis infection an investigation stimulated by the illness ant! death of his wife. The critical wartime need! for tropical medicine research, however, lecT Rene to work on the problem of bacilIary dysentery. While in Boston, the Lowell Institute invites! him to de- liver a series of public lectures on science. The lectures were published as his first book, The Bacterial Cell in Its Relation to Problems of Virulence, Immunity, and Chemotherapy (19451. Writ- ten in a somewhat philosophical manner (perhaps a reflec- tion of the intellectual atmosphere at Harvard), this classic text reviewer! the biochemistry and variability of bacteria and analyzed the mechanisms of pathogenesis in terms of incli- vidual components of the bacterial cell. Despite many invigorating friendships and pleasant social occasions, Rene was lonely, and Boston became linked in his mind with the loss of his wife. When Thomas Rivers and

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RENE JULES DUBOS HONORS AND DISTINCTIONS AWARDS AND MEMBERSHIPS 151 1940 John Phillips Memorial Award, American College of Phy- slclans 1941 1945 Member, National Academy of Sciences 1945 Member, The Century Association 1946 Gordon Wilson Medal, American Clinical and Climatologi- cal Association 1948 Lasker Award, American Public Health Association 1948 Member, Practitioners' Society, New York City 1950 Member, Academia de Ciencias Fisicas, Matematicas, y Nat- urales, Venezuela E. Mead Johnson Award, American Academy of Pediatrics 1951 Trudeau Medal, National Tuberculosis Association 1954 Member, American Philosophical Society 1958 Howard Taylor Ricketts Prize, University of Chicago 1960 Fellow, American Academy of Arts and Sciences 1960 Passano Foundation Award 1960 Robert Koch Medal, Robert Koch Foundation, Berlin 1963 Phi Beta Kappa Award in Science for The Unseen World 1965 Phi Beta Kappa Award in Science for Man Adapting 1966 Arches of Science Award, Pacific Science Center 1968 Two Cultures Award, Flushing High School, New York City 1969 Pulitzer Prize for Nonfiction for So Human an Animal 1969 Benjamin Franklin Fellow, Royal Society of Arts 1970 Harold Terry Clark Medal, Cleveland Museum of Natural History 1972 Frances K. Hutchinson Medal, Garden Club of America 1972 Prix de l'Institut de la Vie, Paris 1973 Bradford Washburn Award, Boston Museum of Science 1975 Cullum Geographical Medal, American Geographic Society 1976 Tyler Ecology Award, Pepperdine University 1979 Wilder Penfield Award, Vanier Institute of the Family 1979 Member, American Academy and Institute of Arts and Let- ters HONORARY DEGREES Forty-one honorary degrees, including three honorary doctorates of medicine, from thirty American and eleven foreign institu- tions, 1941 through 1981

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152 BIOGRAPHICAL MEMOIRS SELECTED BIBLIOGRAPHY The following list contains all of Rene Dubos's books and mono- graphs, but only a selection of his laboratory research journal pub- lications, essays, and lectures. A complete annotated bibliography is being prepared by Carol L. Moberg to be published by The Rockefeller University Press. 1928 Influence of environmental conditions on the activities of cellulose decomposing organisms in the soil. Ecology, 9: 12-27. The decomposition of cellulose by aerobic bacteria. l. Bacteriol', 15:223-34. 1929 The initiation of growth of certain facultative anaerobes as related to oxidation-reduction processes in the medium. J. Exp. Med., 49:559-73. 1930 With Oswald T. Avery. The specific action of a bacterial enzyme on pneumococci of type III. Science, 72:151-52. 1931 With Oswald T. Avery. Decomposition of the capsular polysaccha- ride of pneumococcus type III by a bacterial enzyme. J. Exp. Med., 54:51-71. With Oswald T. Avery. The protective action of a specific enzyme against type III pneumococcus infection in mice. J. Exp. Med., 54:73-89. 1932 Factors affecting the yield of specific enzyme in cultures of the bacillus decomposing the capsular polysaccharide of type III pneumococcus. I. Exp. Med., 55:377-91. 1935 Studies on the mechanism of production of a specific bacterial en- zyme which decomposes the capsular polysaccharide of type III pneumococcus. J. Exp. Med., 62:259-69.

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RENE JULES DUBOS 1936 153 With Karl Meyer and Elizabeth M. Smyth. Action of the lytic prin- ciple of pneumococcus on certain tissue polysaccharides. Proc. Soc. Exp. Biol. Med., 34:816-18. 1937 With Benjamin F. Miller. Determination by a specific, enzymatic method of the creatinine content of blood and urine from nor- mal and nephritic individuals. J. Biol. Chem., 121:457-64. With Benjamin F. Miller. The production of bacterial enzymes ca- pable of decomposing creatinine. l. Biol. Chem., 121 :429-45. 1938 With R. H. S. Thompson. The decomposition of yeast nucleic acid by a heat-resistant enzyme. i. Biol. Chem., 124:501-10. With Robert H. S. Thompson. The isolation of nucleic acid and nucleoprotein fractions from pneumococci. i. Biol. Chem., 125:65-74. 1939 Studies on a bactericidal agent extracted from a soil bacillus. J. Exp. Med., 70:1-17. 1940 The adaptive production of enzymes by bacteria. Bact. Rev., 4: 1-16. The effect of specific agents extracted from soil microorganisms upon experimental bacterial infections. Ann. Intern Med., 13:2025-37. 1941 With Rollin D. Hotchkiss. The production of bactericidal sub- stances by aerobic sporulating bacilli. I. Exp. Med., 73:629-40. With R. B. Little, R. D. Hotchkiss, C. W. Bean, and W. T. Miller. The use of gramicidin and other agents for the elimination of the chronic form of bovine mastitis. Am. I. Vet. Res., 2:305-12. With Rollin D. Hotchkiss. The isolation of bactericidal substances from cultures of Bacillus breves. ]. Biol. Chem., 141:155-62.

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154 BIOGRAPHICAL MEMOIRS 1942 With Rollin D. Hotchkiss. Origin, nature, and properties of gram- icidin and tyrocidine (Mary Scott Newbold Lecture). Trans. Stud. Coll. Physicians Philadelphia, 1 0 (series 4~: 1 1-1 9. With Rollin D. Hotchkiss and Alvin F. Coburn. The effect of gram- icidin and tyrocidine on bacterial metabolism. I. Biol. Chem., 146:421-26. 1943 With June H. Straus and Cynthia Pierce. The multiplication of bacteriophage in viva and its protective effect against an exper- imental infection in Shigella dysenter~ae. ]. Exp. Med., 78:161- 68. 1944 Trends in the study and control of infectious diseases. Proc. Am. Philos. Soc., 88:208-13. 1945 The Bacterial Cell in its Relation to Problems of Virulence, Immunity and Chemotherapy. Harvard University Monographs in Medicine and Public Health, Number 6. Cambridge: Harvard University Press. 1946 With Bernard D. Davis. Factors affecting the growth of tubercle bacilli in liquid media. I. Exp. Med., 83:409-23. With Bernard D. Davis, Gardner Middlebrook, and Cynthia Pierce. The effect of water soluble lipids on the growth and biological properties of tubercle bacilli. Am. Rev. Tuberc., 54:204-12. 1947 The effect of lipids and serum albumin on bacterial growth. l. Exp. Med., 85:9-22. With Cynthia Pierce and Gardner Middlebrook. Infection of mice with mammalian tubercle bacilli in Tween-albumin liquid me- dium. I. Exp. Med., 86: 159-74. With Gardner Middlebrook and Cynthia Pierce. Virulence and

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RENE JULES DUBOS 155 morphological characteristics of mammalian tubercle bacilli. l. Exp. Med., 86: 175-84. With Bernard D. Davis. The binding of fatty acids by serum albu- min, a protective growth factor in bacteriological media. l. Exp. Med., 86:215-28. 1948 Bacterial and Mycotic Infections of Man. Philadelphia: Lippincott. (2d ed. 1952; 3d ed. twith James G. Hirsch] 1958; 4th ed. twith James G. Hirsch] 19651. With Gardner Middlebrook. The effect of wetting agents on the growth of tubercle bacilli. I. Exp. Med., 88:81-88. 1950 Louis Pasteur: Free Lance of Science. Boston: Little, Brown. Re- printed: New York: Charles Scribner's Sons (1976~; New York: Da Capo Press ~ 1986~. With Frank Fenner and Cynthia H. Pierce. Properties of a culture of BCG grown in liquid media containing Tween 80 and the filtrate of heated serum. Am. Rev. Tuberc., 61:66-76. With Frank Fenner. Production of BCG vaccine in a liquid medium containing Tween 80 and a soluble fraction of heated human serum. I. Exp. Med., 91:261-84. 1952 Microbiology in fable and art. Bacterial. Rev., 16:145-51. With Jean Dubos. The White Plague: Tuberculosis, Man, and Society. Boston: Little, Brown. Reprinted: New Brunswick, N.T.: Rut- gers University Press (1986~. With James G. Hirsch. The effect of spermine on tubercle bacilli. I. Exp. Med., 95:191-208. 1953 With Cynthia H. Pierce and Werner B. Schaefer. Multiplication and survival of tubercle bacilli in the organs of mice. J. Exp. Med., 97: 189-206. Effect of ketone bodies and other metabolites on the survival and multiplication of staphylococci and tubercle bacilli. I. Exp. Med., 98: 145 -55.

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156 BIOGRAPHICAL MEMOIRS The philosopher's search for health. Trans. Assoc. Am. Physicians, 66:31-41. The gold-headed cane in the laboratory. In: National Institutes of Health AnnualLectures, pp.89-102. Washington, D.C.: U.S. Gov- ernment Printing Once. 1954 Biochemical Determinants of Microbial Diseases. Harvard University Monographs in Medicine and Public Health, Number 13. Cam- bridge: Harvard University Press. With James G. Hirsch. The antimycobacterial activity of a peptide preparation derived from calf thymus. I. Exp. Med., 99:55-63. 1955 Second thoughts on the germ theory. Sci. Am., 192:31-35. Effect of metabolic factors on the susceptibility of albino mice to experimental tuberculosis. l. Exp. Med., 101:59-84. 1956 With Russell W. Schaedler. Reversible changes in the susceptibility of mice to bacterial infections. I. Exp. Med., 104:53-84. With Cynthia H. Pierce and Werner B. Schaefer. Differential char- acteristics in vitro and in viva of several substrains of BCG. Am. Rev. Tuberc. Pulm. Dis., 74:655-717. 1957 With Russell W. Schaedler. Effects of cellular constituents of my- cobacteria on the resistance of mice to heterologous infections. J. Exp. Med., 106:703-26. 1958 Infection into disease. Perspect. Biol. Med., 1:425-35. Tulipomania and the benevolent virus. In: Perspectives in Virology, ed. M. Pollard, pp. 291-99. New York: Harper and Row. With Russell W. Schaedler. Effect of dietary proteins and amino acids on the susceptibility of mice to bacterial infections. I. Exp. Med., 108:69-81.

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RENE JULES DUBOS 1959 157 Problems in bioclimatology. Proc. Natl. Acad. Sci. USA, 45:1687- 96. Medical utopias. Daedalus, 88:410-24. Mirage of Health: Utopias, Progress, and Biological Change. World Per- spectives, Vol. 22. New York: Harper & Brothers. Reprinted: New York: Doubleday Anchor (1961~; New York: Harper Pe- rennial Library (1971~; New York: Harper Colophon Books (1979~; New Brunswick, N.J.: Rutgers University Press (1987~. 1960 Pasteur and Modern Science. Garden City, N.Y.: Anchor Books. Re- printed: Madison, Wisc.: Science Tech Press (1988~. 1961 With Russell W. Schaedler. The effect of bacterial endotoxins on the water intake and body weight of mice. I. Exp. Med., 113:921-34. The Dreams of Reason: Science and Utopias (George P. Pegram Lec- ture). New York: Columbia University Press. Evolution of Concepts in the Prevention of Tuberculosis (Baker Lecture). Ann Arbor: University of Michigan School of Public Health and Michigan Tuberculosis Association. Scientist and public. Science, 133: 1207-11. 1962 With Russell W. Schaedler. The effect of diet on the fecal bacterial flora of mice and on their resistance to infection. i. Exp. Med., 115:1161-72. The Torch of Life: Continuity in Living Experience. New York: Simon and Schuster. Reprinted: New York: Pocket Books (1963~; New York: Simon and Schuster (1970~. The Unseen World. New York: The Rockefeller Institute Press in association with Oxford University Press. 1963 The Cultural Roots and the Social Fruits of Science (Condon Lectures). Eugene: Oregon State System of Higher Education.

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158 BIOGRAPHICAL MEMOIRS Escape from the land of the lotus eaters. Teach. Coll. Rec.,64:660- 70. Logic and choices in science. Proc. Am. Philos. Soc., 107:365-74. 1964 Environmental biology. BioScience, 14: 11-14. Biological sciences and medicine. In: The Great Ideas Today, ed. R. Hutchins and M. Adler, pp. 224-71. Chicago: Encyclopaedia Britannica. 1965 With Clara I. Lynch and Cynthia H. Pierce-Chase. A genetic study of susceptibility to experimental tuberculosis in mice infected with mammalian tubercle bacilli. I. Exp. Med., 121: 1051-70. Science and man's nature. Daedalus, 94:223-44. Social determinants of medical knowledge. I. Am. Med. Assoc., 194:1371-73. Humanistic biology. Am. Sch., 34:179-98. Also in: Am. Sci., 53: 4-19. With Maya Pines. Health and Disease. New York: Time, Inc. (2d ed. 1970; 3d ed. 1980~. Man Adapting. New Haven: Yale University Press. Reprinted: 1967, 1980. 1966 The microbiota of the gastrointestinal tract. Gastroenterology, 51: 868-74. Man and His Environment: Biomedical Knowledge and Social Action. PAHO/WHO Scientific Lectures, Publ. No. 131. Washington, D.C.: Pan American Health Organization. Adaptation to the environment and man's future. In: The Control of the Environment, ed. John D. Roslansky, pp. 61-78. Amster- dam: North-Holland Publishing Company. 1967 Scientists alone can't do the job. Sat. Rev., 50:68-71. Individual morality and statistical morality. Ann. Int. Med., 67:57- 60.

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RENE JULES DUBOS 159 1968 Man, Medicine, and Environment. New York: Praeger. Reprinted: New York: Mentor Books (19691. With Russell W. Schaedler and Richard Costello. Lasting biological effects of early environmental influence. I. Conditioning of adult size by prenatal and postnatal nutrition. I. Exp. Med., 127:783-99. With Dwayne C. Savage. Alterations in the mouse cecum and its flora produced by antibacterial drugs. I. Exp. Med., 128:97- 110. So Human an Animal. New York: Charles Scribner's Sons. Re- printed: 1970. The human environment in technological societies. Rockefeller Univ. Rev. July/August: 1-11. 1969 A Theology of the Earth. Washington, D.C.: Smithsonian Institution. Human ecology. WHO Chron., 23:499-504. The diseases of civilization. Milbank Mem. Fund. Q., 47:327-39. 1970 The Genius of the Place (Horace M. Albright Conservation Lecture). Berkeley: University of California School of Forestry and Con- servat~on. Reason Awake: Science for Man. New York: Columbia University Press. The human landscape. Bull. At. Sci., 26:31-37 An Earth Day talk. Mort. Arbor. Q., 6:1-4. 1971 . Toxic factors in enzymes used in laundry products. Science, 173:259-60. Man overadapting. Psych. Today, 4:50 -53. In defense of biological freedom. In: The Biopsychology of Develop- ment, ed. E. Tobach et al., pp. 553-60. New York: Academic Press. Credo of a biologist. i. Rel. Health, 10:313-23.

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160 BIOGRAPHICAL MEMOIRS 1972 A God Within. New York: Charles Scribner's Sons. Reprinted: 1972 and 1976. Humanizing the Earth (B. Y. Morrison Memorial Lecture). Washing- ton, D.C.: USDA Agricultural Research Service. With Barbara Ward. Only One Earth: The Care and Maintenance of a Small Planet. New York: W. W. Norton. Reprinted: New York: Ballantine Books (1973~; New York: W. W. Norton (1983~. 1973 Health and environment ~ fames Perkins Lecture). Am. Rev. Resp. Dis., 108:761-66. From nature to resources or does nature really know best ~ Joseph Wunsch Lecture). Haifa: Technion-lsrael Institute of Technology. 1974 Beast or Angel: Choices That Make Us Human. New York: Charles Scribner's Sons. Reprinted: 1975. Of human diversity (Heinz Werner Lecture). Barre, Mass.: Clark University Press with Barre Publishers. Pasteur's dilemma the road not taken. ASM News, 40:703-9. 1975 The biological basis of urban design. In: Anthropopolis: City for De- velopment, ed. C. Doxiadis, pp. 253-63. New York: W. W. Nor- ton. Wilderness and energy. In: Earthcare Programl/ournal, ed. Vivien Fauerbach, pp. 85-91. New York: The National Audubon So- ciety and the Sierra Club. 1976 The Professor, the Institute, and DNA. New York: The Rockefeller University Press. Symbiosis between the earth and humankind. Science, 193:459- 62. 1977 The Resilience of Ecosystems. Rome: Accademia Nazionale dei Lincei. Creative adaptations to the future. In: Aspects of American Liberty,

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REN E ~ U LE S D U B O S 161 ed. George Corner, pp. 162-73. Philadelphia: The American Philosophical Society. 1978 The Resilience of Ecosystems: An Ecological View of Environmental Res- toration (Reuben G. Gustavson Lectures). Boulder, Colo.: Colo- rado Associated University Press. Health and creative adaptation. Hum. Nat., 1:74-82. Biological memory, creative associations, and the living earth. In: The Nature of Life, ed. W. H. Heidcamp, pp. 1-21. Baltimore: University Park Press. 1979 Human Development and the Social Environment (Wilder Penfield Lec- ture). Ottawa: The Vanier Institute of the Family. With Jean-Paul Escande. Quest: Reflections on Medicine, Science, and Humanity. New York: Harcourt, Brace, {ovanovich. Nutritional adaptations. Am. I. Clin. Nutr., 32:2623 - 26. 1980 The Wooing of Earth. New York: Charles Scribner's Sons. Reprinted: 1981. Communities of man and nature. Michigan Q. Rev., 19:203-13. 1981 Celebrations of Life. New York: McGraw-Hill. Reprinted: 1982. 1982 Education for the celebration of life: Optimism despite it all. Teach. Coll. Rec., 84:266-76. Shelters their environmental conditioning and social relevance. In: Shelter: Models of Native Ingenuity, ed. James M. Fitch, pp. 9- 15. Katonah, N.Y.: The Katonah Gallery.