Gramicidin: Ushering in the Scientific Era of Antibiotic Discovery and Therapy

Dubos, René
Courtesy of the Rockefeller Archive Center

Human illnesses such as pneumonia, diphtheria, scarlet fever, anthrax, and streptococcal and staphylococcal infections are caused by gram-positive bacteria—bacteria whose cell walls take up a violet stain known as Gram stain. In 1939, René J. Dubos (1901-1982) discovered gramicidin, an antibacterial agent that inhibits the growth of gram-positive bacteria. It was the first antibiotic to be tested clinically, and it was used in topical form to treat wounds and ulcers during World War II. More effective antibiotics soon superceded gramicidin. But Dubos' discovery launched the antibiotic era and prompted other scientists to renew their stalled investigations into penicillin.

Gramicidin crystals, 1939. Courtesy of Dr. Hotchkiss

Dubos was an expert on bacteria that live in soil. He joined the laboratory of Oswald T. Avery in 1927 to search for a soil microbe that would solve a specific problem in Avery's research—a microbe that could break down the polysaccharide capsule of a deadly strain of bacterial pneumonia, just as other soil bacteria digested decaying organic matter in the woods. Dubos proceeded to feed soil samples—actually, the bacteria in them—a diet of purified polysaccaride. In time, he found a bacterium that secreted an enzyme that broke down this material. He used the same method a decade later in a new search for an agent to combat bacterial infections, this time feeding the soil a mixture of gram-positive bacteria. This time, his samples yielded a bacterium called Bacillus brevis, which secreted two substances that killed or inhibited gram-positive bacteria. Biochemist Rollin Hotchkiss helped Dubos characterize the substances in chemical terms. The first, called tyrothricin, was too toxic to be useful clinically. The second, gramicidin, was manufactured commercially and remains in limited use today.

Dubos, René
Courtesy of the Rockefeller Archive Center

René J. Dubos earned a degree from the Institute National Agronomique in France and received the PhD from Rutgers University in 1927. He joined the Rockefeller Institute that year and remained there his entire career except for two years, 1942-1944, when he was at Harvard University. Author of some two dozen books, Dubos is remembered both as a scientist and as an environmentalist who focused on the interrelationships between environmental health and human health. His book, So Human an Animal, won the Pulitzer Prize in 1969. Among many awards and honors, Dubos received the Lasker Award in 1948 and he was elected to the U.S. National Academy of Sciences. He served as an editor of the Journal of Experimental Medicine from 1946 to 1972.

Selected Publications

Dubos RJ. Studies on a bactericidal agent extracted from a soil bacillus: I. Preparation of the agent. Its activity in vitro. 1939. J Exp Med, 1939, 70:1-10

Dubos RJ. Studies on a bactericidal agent extracted from a soil bacillus: II. Protective effect of the bactericidal agent against experimental pneumococcus infections in mice. J Exp Med, 1939, 70:11-17

Hotchkiss RD and Dubos RJ. Bactericidal fractions from an aerobic sporulating bacillus. J Biol Chem, 1940, 136:803-804

Dubos RJ and Hotchkiss RD. The production of bactericidal substances by aerobic sporulating bacilli. J Exp Med, 1941, 73:629-640

Further Reading

Van Epps HL. René Dubos: Unearthing antibiotics. J Exp Med, 2006, 203: 259

Hotchkiss RD. From microbes to medicine: Gramicidin, René Dubos, and the Rockefeller. In Moberg CL and Cohn ZA eds, Launching the Antibiotic Era: Personal Accounts of the Discovery and Use of the First Antibiotics. New York: Rockefeller University Press, 1990

Hirsch JG and Moberg CL. René Jules Dubos, 1901-1982: A Biographical Memoir. Washington, DC: National Academy of Sciences, 1989

Moberg CL. René Dubos, Friend of the Good Earth: Microbiologist, Medical Scientist, Environmentalist, ASM Press, 2005