Salvador Luria and Max Delbruck provide a statistical demonstration that inheritance in bacteria follows Darwinian principles. Particular mutants, such as viral resistance, occur randomly in bacterial populations, even in the absence of the virus. More importantly, they occur in small numbers in some populations and in large numbers in other cultures. The results, known as fluctuation analysis, show that resistance occurs before exposure to the phage and argues against the adaptation hypothesis of mutations. With Delbruck and Hershey, Luria is awarded the Nobel Prize in Medicine or Physiology in 1969
Luria, S. E. and M. Delbruck. 1943. Mutations of bacteria from virus sensitivity to virus resistance. Genetics. 28: 491-511. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.318 [pdf]
R. E. Hungate describes an anaerobic cellulose digesting bacterium in cattle.
Hungate, R. E. 1943. Further experiments on cellulose digestion by the protozoa in the rumen of cattle. Biol. Bull. 84: 157-163.
1944
W. H. Feldman and H. C. Hinshaw at the Mayo Clinic are the first to demonstrate successful treatment of tuberculosis with streptomycin.
Feldman, W. H. and H. C Hinshaw. 1944. Effects of streptomycin on experimental tuberculosis in guinea pigs. A preliminary report. Proc. Staff Meet. , Mayo Clin. December 24, 1944. 19: 593-599.
Oswald Avery, Colin MacLeod, and Maclyn McCarty show that DNA is the transforming material in cells. They use the observations of Griffith and show the transformation of Streptococcus pneumoniae from an avirulent phenotype to a virulent phenotype is the result of the transfer of DNA from dead smooth organisms to live rough ones. They also show that the transforming principle is destroyed by pancreatic deoxyribonuclease, which hydrolyzes DNA, but is not affected by pancreatic ribonuclease or proteolytic enzymes. Macleod was Avery's research assistant until 1941. By the time he left, he and Avery suspected that the vital substance in bacterial transformation was DNA. McCarty confirmed their hypothesis.
Avery, O. T., C. M. Macleod, and M. McCarty. 1944. Studies on the chemical nature of the substance inducing transformation of pneumonococcal types. Induction of transformation by a deoxyribo-nucleic acid fraction isolated from pnuemococcus type III. J. Exp. Med. 79: 137-157. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.116 [pdf]
Albert Schatz, E. Bugie, and Selman Waksman discover streptomycin, soon to be used against tuberculosis. Streptomycin has the same specific antibiotic effect against gram negative microorganisms as penicillin does on gram positives. Waksman is awarded the Nobel Prize in Medicine or Physiology in 1952
Schatz, A., E. Bugie, and S. A. Waksman. 1944. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc. Soc. Exp. Biol. Med. 55: 66-69.
Ira L. Baldwin, in his 1944 Presidential Address to the Society, provides an interesting mid-century perspective on the challenges facing microbiologists.
Salvador Luria and Alfred Day Hershey demonstrate that bacteriophages mutate, thereby making it difficult to develop immunity to such things as flu and colds. They also introduce criteria for distinguishing mutations from other modifications. With Delbruck and Luria, Hershey is awarded the Nobel Prize in Medicine or Physiology in 1969
Luria, S. E. 1945. Mutation of bacterial viruses affecting their host range. Genetics 30: 84-99.
Colin MacLeod, Richard Hodges, Michael Heidelberger, and William Bernard show that an isolated capsular polysaccharide can immunize against Nesseria meningtitis. The vaccine is finally approved in 1977 after extensive international testing.
MacLeod, C., R. Hodges, M. Heidelberger, and W. Bernhard. 1945. Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J. Exp. Med. 82: 445-465.
1946
Joshua Lederberg and Edward L. Tatum publish on conjugation in bacteria. The proof is based on the generation of daughter cells able to grow in media that cannot support growth of either of the parent cells. Their experiments showed that this type of gene exchange requires direct contact between bacteria. At the time Lederberg began studying with Tatum, scientists believed that bacteria reproduced asexually, but from the work of Beadle and Tatum, Lederberg knew that fungi reproduced sexually and he suspected that bacteria did as well.
Lederberg, J. and E. L. Tatum. 1946. Gene recombination in Eschericia coli. Nature. 58: 558.
1947
Armin Braun shows that A. tumefaciens introduces a factor into plant cells that permanently transforms them into cancer cells.
Braun, A.C. 1947. Thermal studies on the factors responsible for tumour initiation in crown gall. Am. J. Botany 34:234-240
1948
Mary Shorb's Lactobacillus lactis assay is employed at Merck & Co. to guide purification and crystallization of vitamin B12 from Streptomyces griseus culture. B12 is applied to the treatment of pernicious anemia in man, and as the animal protein factor, the promotion of growth in farm animals.
Shorb, M. S. 1948. Activity of vitamin B12 for the growth of Lactobacillus lactis. Science 107: 397.
1949
Microbiologist John Franklin Enders, virologist Thomas H. Weller and physician Frederick Chapman Robbins together develop a technique to grow polio virus in test tube cultures of human tissues. This approach gave virologists a practical tool for the isolation and study of viruses. . Enders, Weller, and Robbins were awarded the Nobel Prize in Medicine or Physiology in 1954
Enders, J. F., T. H. Weller, and F. C. Chapman. 1949. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science 109: 85-87.
Medical mycologist Chester Emmons confirms what many had suspected, that Histoplasma capsulatum resides in soil, by culturing the organism from rat burrows.
Emmons, C. W. 1949. Isolation of Histoplasma capsulatum from soil. U. S. Pub. Hlth. Rep. 64: 892-896.
1950
Robert Hungate publishes a description of the roll-tube culture technique, which permits culturing anaerobes. The procedure eliminates oxygen by underlaying with it with carbon dioxide and then introducing agar. This is a key advance in studying anaerobic bacteria from cow rumen..
Hungate, R. E. 1950. The anaerobic mesophilic cellulolytic bacteria. Bact. Rev. 14: 1-49.
Andre Lwoff and Louis Siminovitch demonstrate that irradiation with ultra-violet light terminates the lysogenic state in bacteria and permits bacteriophage to replicate and then lyse the host cell. This opens the field of lysogeny to molecular analysis. With Jacob and Monod, Lwoff is awarded the Nobel Prize in Medicine or Physiology in 1965
Genetics at the Institute Pasteur: Substance and Style, ASM News 53, 1987. p.547 [pdf].
A. Lwoff, L. Siminovitch, and N. Kjeldgaard. 1950. Comptes Rendus. 231:190-91. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.470 [pdf]
1952
Joshua Lederberg and Esther Lederberg publish their replica plating method and provide firm evidence that mutations in bacteria yielding resistance to antibiotics and viruses are not induced by the presence of selective agents. Replica plating or transfer of specific physical isolates allows for rapid screening of large numbers of genetic markers. With Beadle and Tatum, J. Lederberg is awarded the Noble Prize in Medicine or Physiology in 1958
Bacterial Variation Since Pasteur, ASM News 58, 1992. p.261 [pdf]
Lederberg, J. and E. Lederberg. 1952, Replica plating and indirect selection of bacterial mutants. J. Bact. 63: 399-406.
Joshua Lederberg uses the term plasmid to describe extranuclear genetic elements that replicate autonomously.
Lederberg, J. 1952. Cell genetics and hereditary symbiosis. Physiol. Rev. 32: 403-430.
Joshua Lederberg and Norton Zinder report on transduction, or transfer of genetic information by viruses. They show that a phage of Salmonella typhimurium can carry DNA from one bacterium to another.
Zinder, N and J. Lederberg, 1952. Genetic exchange in Salmonella. J. Bact. 64: 679-699.
Renato Dulbecco shows that single particles of an animal virus can produce plaques. With Baltimore and Temin, Dulbecco is awarded the Nobel Prize in Mediicne and Physiology in 1975
Dulbecco, R. 1952. Production of plaques in monolayer tissue cultures by single particles of an animal virus. Proc. Natl. Acad. Sci. USA. 38: 747-752. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.494 [pdf]
Marvin Bryant isolates spirochetes from cattle rumen.
Bryant, M. 1952. The isolation and characteristics of a spirochete from the bovine rumen. J. Bacteriol. 64: 325-335.
Alfred Hershey and Martha Chase suggest that only DNA is needed for viral replication. They use radioactive isotopes 35S to track protein and 32P to track DNA and show that progeny T2 bacteriophage isolated from lysed bacterial cells have the labeled nucleic acid. Further, most of the labeled protein doesn't enter the cells but remains attached to the bacterial cell membrane.
Hershey, A. D. and M. Chase. 1952. Independent functions of viral protein and nucleic acid in growth of bacteriophage. J. Gen. Physiol. 36: 39-56. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p. 474 [pdf]
Salvador Luria and Mary Human, and independently Jean Weigle, describe a non-genetic heritable variation in bacteriophage imposed on the host in which it was grown. They call this phenomenon host-controlled modification and note that the incorrectly modified phage are "restricted" in the inappropriate host. This later leads to study of bacterial systems of restriction and modification, and eventually the discovery of restriction endonucleases.
Luria, S.E. and M. Human. 1952. A nonhereditary, host-induced variation of bacterial viruses. J. Bact. 64: 557-569.
William Hayes proposes that bacterial conjugation involves the unidirectional transfer of genes from a donor to a recipient cell. Until then, most microbiologists believed that there was either a fusion of cells or an exchange of genetic information. Contemporaneous with Cavalli, Lederberg, and Lederberg, he also shows that a fertility factor, F, a non-chromosomal plasmid, is present only in donor cells.
Lederberg, J., L.L. Cavalli, and E. M. Lederberg. 1952. Sex compatibility in Escherichia coli. Genetics 37: 720-730.
Hayes, W. 1952. Recombination in Bact.coli. K-12: unidirectional transfer of genetic material. Nature 169: 118-119.
James T. Park and Jack L. Strominger conclude that penicillin acts by inhibiting murein synthesis in the cell wall. This is the first discovery of the mode of action of a natural antibiotic.
Park, J. T. 1952. J. Biol. Chem. 194: 877, 885, 897.
1953
James Watson and Francis Crick publish a description of the double-helix structure of DNA. The paper acknowledges that the authors were "stimulated by knowledge of the unpublished experimental results of" Maurice Wilkins and Rosalind Franklin, whose x-ray crystallography images of DNA suggested the structure. Franklin died in 1958; Watson, Crick and Wilkins are awarded the Nobel Prize in Physiology or Medicine in 1962.
Watson, J. D. and F. H. C. Crick, 1953. Molecular structure of nucleic acids: a structure for desoxyribonucleic acid. Nature 171: 737-738.
Jonas Salk begins preliminary testing of polio vaccine. The vaccine is composed of three types of killed virus.
Salk, J. E. 1953. Studies in human subjects on active immunization against poliomyelitis. A preliminary report of experiments in progress. JAMA. 151: 1081.
Elizabeth Lee Hazen and Rachel Fuller Brown develop the first useful fungal antibiotic, NYSTATIN. The drug is developed through a long-distance collaboration with Brown in Albany and Hazen in New York City.
Hazen, E. L., R. F. Brown, and A. Mason. 1953. Protective action of Fungicidin (Nystatin) in mice against virulence enhancing activity of oxytetracycline on Candida albicans. Antibiotics & Chemother. 3: 1125.
1955
H. Edwin Umbarger adds isoleucine to Escheria coli cells growing on minimal glucose and shows that synthesis of isoleucine by the cell is blocked. Arthur Pardee shows the same inhibition pattern with pyrimidines. This finding provides evidence for feedback inhibition.
Umbarger, H. E., and B. Brown. 1955. Isoleucine and valine metabolism in Escherichia coli. Antagonism between isoleucine and valine. J. Bact. 70: 241-248.
Pardee, A. D. 1955. Effect of energy supply on enzyme induction by pyramidine requiring mutants of Escherichia coli. J. Bact. 69: 233-239.
Salvador Luria and Max Delbruck provide a statistical demonstration that inheritance in bacteria follows Darwinian principles. Particular mutants, such as viral resistance, occur randomly in bacterial populations, even in the absence of the virus. More importantly, they occur in small numbers in some populations and in large numbers in other cultures. The results, known as fluctuation analysis, show that resistance occurs before exposure to the phage and argues against the adaptation hypothesis of mutations. With Delbruck and Hershey, Luria is awarded the Nobel Prize in Medicine or Physiology in 1969
Oswald Avery, Colin MacLeod, and Maclyn McCarty show that DNA is the transforming material in cells. They use the observations of Griffith and show the transformation of Streptococcus pneumoniae from an avirulent phenotype to a virulent phenotype is the result of the transfer of DNA from dead smooth organisms to live rough ones. They also show that the transforming principle is destroyed by pancreatic deoxyribonuclease, which hydrolyzes DNA, but is not affected by pancreatic ribonuclease or proteolytic enzymes. Macleod was Avery's research assistant until 1941. By the time he left, he and Avery suspected that the vital substance in bacterial transformation was DNA. McCarty confirmed their hypothesis.
Albert Schatz, E. Bugie, and Selman Waksman discover streptomycin, soon to be used against tuberculosis. Streptomycin has the same specific antibiotic effect against gram negative microorganisms as penicillin does on gram positives. Waksman is awarded the Nobel Prize in Medicine or Physiology in 1952
Microbiologist John Franklin Enders, virologist Thomas H. Weller and physician Frederick Chapman Robbins together develop a technique to grow polio virus in test tube cultures of human tissues. This approach gave virologists a practical tool for the isolation and study of viruses. . Enders, Weller, and Robbins were awarded the Nobel Prize in Medicine or Physiology in 1954
Joshua Lederberg and Esther Lederberg publish their replica plating method and provide firm evidence that mutations in bacteria yielding resistance to antibiotics and viruses are not induced by the presence of selective agents. Replica plating or transfer of specific physical isolates allows for rapid screening of large numbers of genetic markers. With Beadle and Tatum, J. Lederberg is awarded the Noble Prize in Medicine or Physiology in 1958
James Watson and Francis Crick publish a description of the double-helix structure of DNA. The paper acknowledges that the authors were "stimulated by knowledge of the unpublished experimental results of" Maurice Wilkins and Rosalind Franklin, whose x-ray crystallography images of DNA suggested the structure. Franklin died in 1958; Watson, Crick and Wilkins are awarded the Nobel Prize in Physiology or Medicine in 1962.