Publication of The Microbe's Contribution to Biology by A. J. Kluyver and C. B. Van Neil. The work hints at a future explosion of knowledge concerning the regulation of metabolism and its genetic machinery-A prophecy that will come true in less than two decades.

Charles E. Smith and his colleagues, by correlating the results of the analysis of 39,500 sera of patients with coccidiodomycosis, establish the usefulness of serology in the diagnosis and prognosis of coccidiodomycosis.

Smith, C. E., M. T. Saito, and S. A. Simmons. 1956. Pattern of 39500 serologic tests in coccidioidomycosis. JAMA 160: 546-552.

D. L. D. Caspar and Rosalind Franklin independently show the location of the ribonucleic acid within the protein capsid in tobacco mosaic virus.

Caspar, D. L. D. 1956. Radial density Distribution in the Tobacco Mosaic Virus particle. Nature 177: 928.

Franklin, R. 1956. Location of the ribonucleic acid in the tobacco mosaic virus particle. Nature 177: 929.

G. Schramm and A. Gierer show that RNA from tobacco mosaic virus is infectious and by itself can cause the disease and result in new viral particles..

Gierer, A. and G. Schramm. 1956. Infectivity of ribonucleic acid from tobacco mosaic virus. Nature 177: 702-702. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.502
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Seymour Benzer shows that recombination can occur between mutations within the same gene. He maps the mutations with the rII gene of phage T4 and demonstrates that genes are linear arrays of mutable sites.

Benzer, S. 1955. Fine structure of a genetic region in bacteriophage. Proc. Natl. Acad. Sci. USA 41: 344-354. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p. 340 [pdf]

Alick Isaacs and Jean Lindemann discover interferon, an antiviral protein produced by the body to fight viral infections. The first experiments take place with chick embryo tissue cultures infected with influenza virus. The interferon protects adjacent cells against the virus.

Isaacs, A., and J. Lindenmann. 1957. Virus interference; I. The interferon. Proc. Roy. Soc. Series B 147: 258-267. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.506 [pdf]

D. Carleton Gajdusek proposes that a slow virus is responsible for the wasting disease kuru. He shows that the course of the disease is similar to that of scrapie, which is transmitted among sheep. He also shows that kuru can be transmitted to chimpanzees.With Blumberg, Gajdusek is awarded the Nobel Prize in Medicine or Physiology in 1976

1976 Nobel Prize

Gajdusek, D. C. and V. Zigas. 1957. Degenerative disease of the central nervous system in New Guinea. The endemic occurrence of "kuru" in the native population. N. Engl. J. Med. 257: 974-978.

Heinz Fraenkal-Conrat demonstrates that viral RNA can act as a source of genetic information by mixing viral coat proteins and RNA from two viruses and showing that lesions on tobacco plants are entirely dependent on the source of RNA in the reassembled virus.

Fraenkel-Conrat, H. and R. C. Williams. 1957. Virus reconstitution : combination of protein and nucleic acid from different strains. Biochim. Biophys. Acta. 24: 87.

Shuko Kinoshita, S, Udaka, and M. Shimono discover that bacteria can be used to produce monosodium glutamate. This leads to a new industry; the microbial production of amino acids for human and animal nutrition as well as for food flavoring.

Kinoshita, S., K. Tanaka, S. Udaka, and S. Akita. 1957. Proc. Intern. Symposium Enzyme Chem. 464-468.

Francois Jacob and Elie Wollman provide evidence of the circular nature of the chromosome in Escherichia coli after analyzing data from interrupted mating experiments.

Wollman, E. and F. Jacob. 1957. Sur les processus de conjugaison et de reconbinaison chez Escherichia coli. Ann. Inst. Pasteur 93: 323-339.

The Soviet delegation to the World Health Organization proposes a global crusade to eradicate smallpox. Approved in 1959, the program finally begins in 1967.

Joseph H. Burkhalter and Robert Seiwald make an essential contribution to the identification of antigens by developing the first antibody labeling agent, flourescein isothiocyanate (FITC). Widespread use of FITC catalyzed the generation of other labeling procedures such as the radio-immunoassay and enzyme-linked immuno-absorbant assay.

Riggs, J. L., R. J. Seiwald, J. H. Burkhalter, et al. 1958. Isothiocyanate compounds as flourescent labeling agents for immune serum. Am. J. Path. 34: 1081-1097.

Matthew Meselson and Franklin Stahl use density gradient equilibrium centrifugation to show that the two parental strands of DNA untwist during replication and combine with a newly synthesized daughter strand, just as predicted by Watson and Crick.

Meselson, M. and F. Stahl. 1958. The replication of DNA in Escherichia coli. Proc. Natl. Acad. Sci. USA 44: 671-682.

Ole Maaloe, Moselio Schaechter, and Nils O. Kjeldgard establish that bacteria can grow in a continuum of physiological states determined by the growth rate. This starts a new discipline, bacterial growth physiology.

Schaechter, M., O. Maaloe, and N. O. Kjeldgard. 1958. Dependency on medium and temperature of cell size and chemical composition during balanced growth of Salmonella typhimurium. J. Gen. Microbiol. 19: 152.

O. Sawada and others demonstrate that antibiotic resistance can be transferred between Shigella strains and Escherichia coli strains by extrachromosomal plasmids. The transfer does not involve either transformation or transduction.

Ochiai, K., T. Yamanaka, K. Kimura, and O. Sawada. 1959. Nippon lji. 1861: 34.

Arthur Pardee, Francois Jacob, and Jacque Monod show that the enzyme beta-galactosidase is induced by changes in culture conditions. This is the first example of negative control of induction and is due to the action of a repressor protein. This set the stage for other experiments aimed at further delineating the interaction of a regulatory protein with a site on DNA to control the expression of other genes.

Pardee, A., F. Jacob, and J. Monod. 1959. The genetic control and cytoplasmic expression of 'inducibility' in the synthesis of beta-galactosidase by E. coli. J. Mol. Biol. I: 165. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.368 [pdf]

Maxwell Finland, W. F. Jones, Jr., and M. W. Barnes comment on the development of antibiotic resistance, as a response to the introduction of antibacterial agents.

Hirsch, H. and M. Finland. 1959. Antibacterial activity of serum of normal subjects after oral doses of demethylchlortetracycline, chlortetracycline and oxtetracycline. N. Engl. J. Med. 260: 1099-1104.

Peter Mitchell proposes the chemiosmotic theory in which a molecular process is coupled to the transport of protons across a biological membrane. He argues that this principle explains ATP synthesis, solute accumulations or expulsions, and cell movement (flagellar rotation). Mitchell is awarded the Nobel Prize in Chemistry in 1978

1978 Nobel Prize

Peter Mitchell and the Chemiosmotic Theory, ASM News 63, 1997. p.13 [pdf]

Mitchell, P., and J. Moyle. 1959. Permeability of the envelopes of Staphylococcus aureus to some salts, amino acids and non-electrolytes. J. Gen. Microbiol. 20: 434-441.

R.L. Riley, C.C. Mills, and W. Nyka prove that pulmonary tuberculosis is disseminated as an aerosol and so affected individuals are contagious. They used guinea pigs as the animal model and exposed them to air from patients with active pulmonary tuberculosis.

R.L. Riley, C.C. Mills, W. Nyka, N. Weinstock, P.B. Storey, L.U. Sultan, M.C. Riley, and W.F. Wells. Aerial disseminations of pulmonary tuberculosis. A two-year study of contagion in a tuberculosis ward. 1959. Amer. J. Hyg. 70:185-96 In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.26 [pdf]

Arthur Kornberg demonstrates DNA synthesis in cell-free bacterial extracts and later shows that a specific enzyme is necessary to link the nucleotide precursors of DNA. The enzyme works only in the presence of a DNA template.

Kornberg, A. 1960. Biologic synthesis of deoxyribonucleic acid. Science 131: 1503-1508.

Francois Jacob, David Perrin, Carmen Sanchez and Jacques Monod propose the operon concept for control of bacteria gene action. Jacob and Monod later propose that a protein repressor blocks RNA synthesis of a specific set of genes, the lac operon, unless an inducer, lactose, binds to the repressor. With Lwoff, Jacob and Monod are awarded the Noble Prize in Medicine or Physiology in 1965

1965 Nobel Prize

Jacob, F., D. Perrin, C. Sanchez, and J. Monod. 1960. L'operon: Groupe de genes a l'expression coordonne par un operateur. Compt. Rendu. Acad. Sci. 245: 1727-`729.

The oral polio vaccine developed by Albert Sabin is approved for use in the U. S. after trials are conducted abroad on more than 100 million people.

Benjamin D. Hall and Sol Speigleman show that singled stranded T2 phage DNA can form a hybrid with RNA from T2 infected Escherichia coli, thus demonstrating the potential of DNA-RNA hybridization methods.

Hall, B. D. and S. Speigelman. 1961. Sequence complemetarity of T2-DNA and T2-specific RNA. Proc. Natl. Acad. Sci. USA 47: 137-146.

John Holland reports on the correlation between receptors for poliovirus on the surface of cells and the known pathogenicity of the virus for humans and animals.

Holland, J. J. 1961. Receptor affinities as major determinants of enterovirus tissue tropisms in humans. Virology 15: 312-326.

Francis Crick, Sydney Brenner, and colleagues propose the existence of transfer RNA that uses a three base code and mediates in the synthesis of proteins.

Crick, H. F. C., L. Barnett, S. Brenner, and R. J. Watts-Tobin. 1961. General nature of genetic code for proteins. Nature 192: 1227-1232. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.384 [pdf]

Marshall Nirenberg and J.H. Matthaei observe that a synthetic polynucleotide, poly U, directs the synthesis of a polypeptide composed only of phenylalanine. They conclude that the triplet UUU must code for phenylalanine. This is the start of successful efforts to decipher the genetic code. With Robert Holley and Har Gobind Khorana, Nirenberg is awarded the Noble Prize in Medicine or Physiology in 1968

1968 Nobel Prize

Marshall Nirenberg Collection

Nirenberg, M. W. and H. J. Matthaei. 1961. The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Proc. Natl. Acad. Sci. USA 47: 1589.

Sydney Brenner, Francois Jacob and Matthew Meselson use phage infected bacteria to show that ribosomes are the site of protein synthesis and confirm the existence of a messenger RNA. They demonstrate infection of Escherichia coli by phage T4 stops cell synthesis of host RNA and leads to T4 specific synthesis. The T4 RNA attaches to cellular ribosomes and directs protein synthesis.

Brenner, S., F. Jacob, and M. Meselson. 1961. An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature. 190: 576-581.

Brian McCarthy and E. T. Bolton describe a method for quantitative determination of the extent of hybridization of DNA or RNA from different biological sources. By this means, it is possible to determine the extent of sequence homology in the genomes of the organisms.

Aronson, A. and B. J. McCarthy. 1961. Studies of E. coli ribosomal RNA and its degradation products. Biophys. J. 1: 215-226.

Daniel Nathans, Norton Zinder, and colleagues use E. coli cell-free system together with bacteriophage f2 RNA to produce viral coat protein identical in amino acid sequence to that isolated directly from the virus. With Arber and Smith, Nathans is awarded the Nobel Prize in Medicine or Physiology in 1978

1978 Nobel Prize

Nathans, D., G. Notani, J. H. Schwartz, and N. D. Zinder. 1962. Biosynthesis of the coat protein of coliphage f2 by E. coli extracts. Proc. Natl. Acad. Sci. USA 48: 1424-1431.

James Gowans determines that small lymphocytes can initiate both cellular and humoral immune responses to specific antigens. They are the units of selection in the Burnet theory of clonal selection.

Gowans, J.L., D.D. McGregor, D.M. Cowen, and C.E. Ford. 1962. Initiation of Immune Responses by Small Lymphocytes. Nature 196:651-55 In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.140 [pdf]

Baruch Blumberg describes the "Australia Antigen" (hepatitis B antigen) that is found in the blood of viral hepatitis sufferers. Together with Irving Millman, Blumberg develops a vaccine against the virus. Some consider it to be the first vaccine against cancer because of the strong association of hepatitis B with liver cancer. With Gadjusek, Blumberg is awarded the Nobel Prize in Medicine or Physiology in 1976

1976 Nobel Prize

Blumberg, B. S. and N. M. Riddell. 1963. Inherited antigenic differences in human beta lipo-proteins. A second antiserum. J. Clin. Invest. 42: 867-875.

Robin Holliday proposes that genetic recombination in yeast proceeds through two single stranded breaks made simultaneously at the same sites on the two DNA molecules to be recombined. The model appears to work for recombination of all organisms.

Holliday, R. 1964. A mechanism for gene conversion in fungi. Gen. Res. 5: 282-304.

Charles Yanofsky and coworkers define the relationship between the order of mutatable sites in the gene coding for Escherichia coli tryptophan synthetase and the corresponding amino acid replacements in the enzyme. It worked well for tyrptophan synthetase because the enzyme has two subunits, one of which could b emutated. The missense mutants in the alpha subunt could be mapped and related to the genetic fine strucutre of the gene. The property of correlating a mutation with an amino acid replacement is called colinearity.

Yanofsky, C., B.C. Carlton, J.R. Guest, D.R. Helinski, and U. Henning. 1964. On the colinearity of gene structure and protein structure. Proc. Nat'l. Acad. Sci. 51:266-74 In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.392 [pdf]

Earl Stadtman and colleagues demonstrate that methyl-B12 is involved in acetate synthesis and is the first step in the acetyl-Coa pathway.

J.M. Poston, K. Kuratomi, and E.R. Stadtman. 1964. Methyl-vitamin B12 as a source of methyl groups for the syntesis of acetate by cell-free of Clostridium thermoaceticum. Ann. N.Y. Acad. Sci. 112:804-06. InMicrobiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.210 [pdf]

Sol Speigleman and I. Haruna show that a virally coded replicase from phage Q beta can synthesize infectious viral RNA from precursor nucleotides. This establishes the concept of viral RNA acting as a genome.

Spiegelman, S., I. Haruna, I. B. Holland, G. Beaudreau, and D. Mills. 1965. The synthesis of a self-propagating and infectious nucleic acid with a purified enzyme. Proc. Natl. Acad. Sci. USA 54: 919.

Ellis Englesberg, J. Irr, J. Power, and N. Lee add to the repertoire of regulatory control mechanisms by showing that an activator protein is required for the expression of the genes determining arabinose metabolism in E. coli.

Englesberg, E., J. Irr, J. Power, and N. Lee. 1965. Positive control of enzyme synthesis by gene C in the L-arabinose system. J. Bact. 90: 946-957. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.400 [pdf]

The key to the whole field of nucleic acid -based identification of microorganisms was the introduction of the concept of molecular systematics using proteins and nucleic acids by the American Nobel laureate Linus Pauling. Since the sequence of nucleic acids in a particular microorganism is extremely conservative constant, even over geological time, and the DNA and RNA molecules are relatively stable, they are excellent materials for the detection and identification of microorganisms.

Zuckerkandl, E., and L. Pauling. "Molecules as Documents of Evolutionary History." Journal of Theoretical Biology 8:357-366