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Dubos, René (1901-1982)

Dubos, RenÉ (1901-1982)

French-born American microbiologist

René Dubos was a distinguished microbiologist whose pioneering work with soil-dwelling bacteria paved the way for the development of life-saving antibiotic drugs. Widely acclaimed for his discovery of tyrothricin, a chemical substance capable of destroying dangerous staphylococcus, pneumococcus, and streptococcus bacteria in both humans and animals, Dubos later turned to the study of tuberculosis and the role of physiological, social, and environmental factors in an individual's susceptibility to infection. In the 1960s, Dubos's interest in the effects of the total environment on human health and well-being prompted him to give up his laboratory work at New York's Rockefeller Institute for Medical Research to concentrate on writing and lecturing on ecological and humanitarian issues.

Over the years, Dubos produced a number of popular books on scientific subjects, including So Human an Animal, the 1968 Pulitzer-Prize winner for general nonfiction, and Only One Earth: The Care and Maintenance of a Small Planet, which formed the basis for the United Nations Conference on the Human Environment in 1992. Dubos's greatest concern was not man's inability to adapt to pollution, noise, overcrowding, and the other problems of highly industrialized societies, but rather the ease with which this adaptation could occur and its ensuing cost to humanity. "It is not man the ecological crisis threatens to destroy, but the quality of human life," Dubos wrote in Life magazine. "What we call humanness is the expression of the interplay between man's nature and the environment, an interplay which is as old as life itself and which is the mechanism for creation on Earth."

Dubos was born in Saint-Brice-sous-Foret, France, the only child of Georges Alexandre and Adeline Madeleine de Bloedt Dubos. Young Dubos spent his early years in the farming villages of Ile-de-France, north of Paris. Amongst the rolling hills and agricultural fields, Dubos developed a keen appreciation for the influence of landscape on the human spirit, a subject that would come to dominate his thoughts in later years. A bout with rheumatic fever at the age of ten both restricted Dubos's physical activity and enhanced his contemplative nature. When Dubos was 13, his father moved the family to Paris to open a butcher shop; a few months later, Georges Dubos was called to military service in World War I, leaving his wife and young son in charge of the business. Despite the best efforts of mother and son, the shop did poorly and the family had a difficult time getting by. Upon completing high school at the College Chaptal in 1919, Dubos had hoped to study history at the university, but the death of his father from head injuries suffered at the front forced him to stay closer to home to look after his mother. Dubos was granted a scholarship to study agricultural science at the Institut National Agronomique in Paris, receiving his bachelor of science degree in 1921. He spent part of the next year as an officer trainee in the French Army, but was soon discharged because of heart problems.

In 1922, Dubos was offered the job of assistant editor at a scholarly journal called International Agriculture Intelligence, published by the International Institute of Agriculture, then part of the League of Nations in Rome. Not long after he arrived in Italy, Dubos came across an article on soil microbes written by the Russian bacteriologist Sergei Winogradsky, who was then associated with the Pasteur Institute in Paris. Winogradsky's contention that microbes should be studied in their own environment rather than in pure, laboratory-grown cultures so intrigued Dubos that he resolved to become a bacteriologist. "This is really where my scholarly life began," he told John Culhane in an interview for the New York Times Magazine. "I have been restating that idea in all forms ever since." Soon after, Dubos happened to meet the American delegate to the International Institute of Agriculture, who convinced him to pursue graduate studies in the United States.

In order to finance his trip, Dubos translated books on forestry and agriculture and gave guided tours of Rome to foreign visitors. He eventually set sail for New York in 1924. During the crossing, Dubos ran into Selman Waksman , head of the soil microbiology division of the State Agricultural Experiment Station at Rutgers University in New Jersey (a man the aspiring scientist had guided around Rome some months before). After the ship docked in New York, Waksman introduced Dubos to his colleagues at Rutgers University, helping the young man secure a research assistantship in soil microbiology. While serving as an instructor in bacteriology over the next three years, Dubos completed work on his doctorate. His thesis, published in 1927, focused on the ways in which various soil microorganisms work to decompose cellulose in paper.

Upon completing his work at Rutgers, Dubos left for the University of North Dakota at Fargo to accept a teaching position in the department of microbiology. Soon after he arrived, however, Dubos received a telegram from the Rockefeller Institute for Medical Research in New York City offering him a fellowship in the department of pathology and bacteriology. Dubos immediately packed his bags, in part because the offer involved work on a project begun by Rockefeller bacteriologist Oswald T. Avery . Avery and his colleagues had been searching for a substance that could break down the semi-cellulose envelope which protects pneumococci bacteria, the microorganisms responsible for lobar pneumonia in human beings, from attack by the body's defense mechanisms. Dubos's bold assertion that he could identify an enzyme capable of decomposing this complex polysaccharide capsule with minimal damage to the host had evidently impressed Avery. With the exception of a two-year period in the early 1940s when he served on the faculty at Harvard Medical School, Dubos remained at the Rockefeller Institute, renamed Rockefeller University in 1965, for the next 44 years.

Guided by the studies of renowned bacteriologist Louis Pasteur , who maintained that any organic substance that accumulated could be broken down by natural energy, Dubos spent his first two years at the Institute searching fields, bogs, and swamps for a bacterium or fungus that could attack and decompose the tough polysaccharide coat surrounding pneumococci bacteria. Unlike other scientific investigators, who used enriched laboratory solutions to cultivate bacteria and force them to produce enzymes , Dubos concocted a solution rich in capsular polysaccharide, which he spread over a variety of soils. In 1929, he succeeded in isolating a swamp-dwelling bacillus which, because of its need for nourishment in an energy-starved environment, had been compelled to produce an enzyme capable of decomposing the polysaccharide capsule and digesting the pneumococci within. The following year Dubos was able to demonstrate the value of this particular enzyme in fighting pneumococcal infections in both animals and humans. The discovery confirmed Dubos's belief that soil bacteria were an important source of anti-infectious agents, inspiring him to search for other disease-fighting microbes.

In 1939, Dubos announced the discovery of a substance called tyrothricin, which had proved effective in fighting staphylococcus, pneumococcus, and streptococcus infections. Produced by the soil microorganism Bacillus brevis, tyrothricin was later found to contain two powerful chemicals, gramicidin and tyrocidine, which, though too toxic for ingestion, found widespread application in the treatment of external conditions, such as infectious lesions in humans and udder infections in cows. Dubos's groundbreaking work prompted scientists from around the world to conduct a wide-ranging search for antibiotic substances in natural environments. This ultimately resulted in a reexamination of the therapeutic properties of penicillinfirst discovered in a bread mold ten years earlier by Alexander Flemingand led to the isolation of a variety of new antibiotics , including streptomycin and the tetracyclines.

The death of Dubos's first wife, Marie Louise Bonnet, from tuberculosis in 1942 had a profound effect upon the scientist's career. "There seemed no reason," he recalled for Culhane. "Why should she get [tuberculosis] in this environment?" After spending two years as a professor of tropical medicine at Harvard Medical School, Dubos returned to the Rockefeller Institute to begin a full-scale investigation of tuberculosis and its causes. Until that time, scientists attempting to study tuberculosis bacilli had been hindered by the fact that laboratory methods of cultivation often modified the organisms to such an extent that they no longer resembled or behaved like the strains that infected humans. By 1947, however, Dubos had discovered that by adding a common detergent to the culture medium, he could raise bacilli so quickly and in such large quantities that they had little chance to mutate. This enabled researchers to study the microorganism more closely and develop the highly effective Bacillus Calmette-GuÉrin, or BCG, vaccine .

During the course of his research with tuberculosis, Dubos focused on the importance of heredity, nutrition, physiology, and social and emotional trauma on an individual's vulnerability to infection. He used his wife's case as his first example. A careful examination of her early health records revealed that she had suffered from tuberculosis as a child. Although his wife recovered from the acute attack, Dubos became convinced that the emotional upheaval of World War II and her concern for her family's safety in France had served to weaken her and reawaken the dormant germ. Some years later, Dubos's second wife's battle with tuberculosis and her subsequent recovery prompted the couple to collaborate on The White Plague: Tuberculosis, Man, and Society, a nontechnical account of the disease. Published in 1952, the book provided additional evidence linking tuberculosis with certain environmental conditions, such as inadequate nourishment and sudden economic or social disturbances.

Later, Dubos's interest in the effects of the total environment on human health encouraged him to become involved with the sociomedical problems of poor communities and to speak out on the dangers of pollution, as well as social, economic, and spiritual deprivation. By 1964, he had become a leading spokesman for the fledgling environmental movement and an outspoken critic of what he viewed as the narrow, short-range approach used by most biologists.

According to Dubos, the problems of technologically advanced societies posed an equal, if not greater, threat to human survival. Two of Dubos's most popular books, Man Adapting and So Human an Animal, examine the close relationship between environmental conditions and man's physical, mental, and spiritual development, emphasizing the dangers inherent in adapting to a polluted, highly mechanized, highly stressful environment. "Wild animals can survive in zoos, but only at the cost of losing the physical and behavioral splendor they possess in their natural habitat," he wrote in Life. "Similarly, human beings can survive in the polluted cage of technological civilization, but in adapting to such conditions, we may sacrifice much of our humanness." Dubos also warned against introducing new substances, such as laundry detergents containing potentially dangerous enzymes, into the American marketplace without thorough testing. Unlike many environmentalists, however, Dubos maintained an enormous faith in both the ability of nature to recover from man's abuses and man's own capacity to recognize and learn from mistakes.

Dubos became a naturalized American citizen in 1938. Although he maintained a laboratory and an apartment in New York City, Dubos spent most weekends at his large estate in Garrison, New York. There, he and his wife planted trees, raised vegetables, and enjoyed long walks in the scenic Hudson River Valley. Over the years, Dubos earned numerous awards for his work, including the Modern Medicine Award, 1961, the Phi Beta Kappa Award, 1963, and the Tyler Ecology Award, 1976; he also received more than thirty honorary degrees from various colleges and universities. A member of professional organizations such the National Academy of Sciences, Dubos was also appointed by President Richard M. Nixon in 1970 to serve on the Citizens' Advisory Committee on Environmental Quality. Always eager to make his scientific and philosophical ideas accessible to people from all walks of life, Dubos continued to write and lecture until shortly before his death from heart failure at age 82 in New York City.

See also History of microbiology; History of public health; History of the development of antibiotics

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Dubos, René

Dubos, René

American bacteriologist 19011982

In 1939 René Dubos launched the antibiotic era by reporting the discovery of gramicidin after the first systematic search for antimicrobial agents. Following this discovery he warned of microbial resistance to antibiotics, completed innovative studies of tuberculosis, expanded investigations into the nature of disease and, ultimately, examined the question of health.

Born near Paris in 1901, Dubos studied agronomy in France and, through a chance meeting with biochemist Selman Waksman, was invited to study soil science at Rutgers University. In his Ph.D. studies, Dubos discovered that local soil characteristics determine which microbes decompose cellulose .

By good fortune again, Dubos joined Oswald Avery of the Rockefeller Institute (now University) who was trying to decompose the polysaccharide capsule surrounding the deadly pneumococcus bacterium. Dubos succeeded by using a soil enrichment technique to find a specific microbial enzyme .

He further discovered this enzyme was produced only if the polysaccharide capsule was the microbe's sole food, a phenomenon now known as an induced enzyme. He described this as "his greatest hour in science . . . one of the most important biological laws I have ever been in contact with."

In 1939, using the same techniques, he found Bacillus brevis, a microbe that digests and destroys other microbes. From it he extracted an antibacterial agent he named tyrothricin that contains two polypeptides he called gramicidin and tyrocidine. Within a few months, he and organic chemist Rollin Hotchkiss described the bacterial, chemical, clinical, and pharmaceutical properties of these antibiotics. This work stimulated two English scientists, Howard Florey and Ernst Chain, to revive the stalled research on penicillin, found accidentally in 1929 by Scottish bacteriologist Alexander Fleming.

In 1942 Dubos warned that bacterial resistance to antibiotics should be expected, saying, "In the analysis of . . . antibacterial agents . . . susceptible bacterial species often give rise with 'training' to variants endowed by great resistance to these agents."

Dubos turned his interest to tuberculosis in 1944. He began a renaissance in studying this disease by creating a culture medium to produce rapid, luxuriant, and well-dispersed growth of bacilli. He pioneered international standards for the BCG vaccination against tuberculosis and described social aspects of the disease in "The White Plague" (1952). Later he investigated how environmental effects of crowding, malnutrition, pesticides, toxins, and stress increase susceptibility to disease.

Dubos observed that people coexist with both good and bad microbes and that disease-producing microbes reside quiescently (dormant) in the body until stress alters resistance. He restated the germ theory, saying a microbe is necessary but not sufficient to cause disease. He concluded that in order to improve one's physical and spiritual well-being, one must first understand and then control one's impact on one's own surroundings.

When he won the Pulitzer prize in 1969 for So Human an Animal, Dubos was thrust into the swelling environmental debate. He became well known for balancing views between those who believe that humans can improve on nature and those who advocate wilderness preservation. Hundreds of lectures and two dozen books evolved from medical considerations of environment and health, to cultural and scientific aspects of medicine, to an ecological philosophy encompassing health of Earth. He coined many aphorisms such as "think globally, act locally" to explain complex issues.

see also Bacterial Diseases; History of Medicine; Natural Selection

Carol L. Moberg

Bibliography

Dubos, René. So Human an Animal. New York: Charles Scribner's Sons, 1968.

, and Jean Dubos. The White Plague: Tuberculosis, Man, and Society. Boston: Little, Brown, 1952.

Moberg, Carol L., and Zanvil A. Cohn. "René Jules Dubos." Scientific American 264, no. 5 (1991): 6674.

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