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What you should know...
Significant Events Of The Last 125 Years
Pasteur introduced the terms
aerobic and anaerobic in describing the growth of yeast at the expense of sugar in the
presence or absence of oxygen. He observed that more alcohol was produced in the absence
of oxygen when sugar is fermented, which is now termed the Pasteur effect.
Pasteur, L. "Animalcules infusoires vivant sans gaz oxygene libre et
determinant des fermentations." Compt. Rend. Acad. Sci. (Paris) 52:344-347,
Thomas H. Huxley's Biogenesis and
Abiogenesis address is the first clear statement of the basic outlines of modern Darwinian
science on the question of the origin of life. The terms "biogenesis" (for life
only from pre-existing life) and "abiogenesis" (for life from nonliving
materials, what had previously been called spontaneous generation) as used by Huxley in
this speech have become the standard terms for discussing the subject of how life
originates. The speech offered powerful support for Pasteur's claim to have experimentally
disproved spontaneous generation. The speech was also Huxley's attempt to define an
orthodox Darwinian position on the question, and attempt to define as
"non-Darwinian" all those Darwin supporters who believed that spontaneous
generation up to the present day was an essential requirement of evolutionary science.
Henry Charlton Bastian was the most prominent leader of that faction of Darwinians, though
Huxley was so successful in defining them out of the story that very few people today even
realize that there WERE Darwinians who were serious, talented evolutionary scientists, yet
also thought abiogenesis was necessary in evolution up to the present day.
James Strick. 1999. Darwinism and the Origin of Life: the Role
of H.C. Bastian in the British Spontaneous Generation Debates, 1868-1873. Journal of the
History of Biology, 32:1-42 [PDF]
Ferdinand J. Cohn contributes
to the founding of the science of bacteriology. In the publication Ueber
Bakterien, he discusses the role of microorganisms in the cycling of elements in
nature. In 1875, Cohn will publish an early classification of bacteria, using the genus
name, Bacillus, for the first time.
Cohn, F. 1872. Ueber Bakterien, die kleinsten lebenden Wesen.
Lüedritzsche Verlagsbuchhandlung Carl Habel, Berlin.
Cohn, F., 1875. Untersuchungen ueber Bakterien. Beitraege zur Biologie der
Planzen 1:127-222 In Milestones in Microbiology: 1556 to 1940, translated and edited by
Thomas D. Brock, ASM Press. 1998, p210 [PDF]
Cohn, a Founder of Modern Microbiology, ASM News 65.
The German botanist Brefeld reported growing fungal colonies from single spores
on gelatin surfaces. Prior to this innovation that resulted in the isolation of pure
culture of microorganisms, pigmented bacterial colonies were isolated by the German
biologist Schroeter on slices of potato incubated in a moist environment.
Brefeld, O. Botanische Untersuchungen uber Schimmelpilze, Heft I, Mucor mucedo,
Chaetocladium Jones ii, Piptocephalis Fresiana: Zygomyceten, Leipzig, 1872.
Schroeter, J. "Ueber einige durch Bacterien gebildete Pigmente." Beitr.
Z. Biol. D. Pflanzen 1:2, 109-126.
Robert Koch publishes a paper on his work with anthrax,
pointing explicitly to a bacterium as the cause of this disease. This validates the germ
theory of disease. Prior, in 1872, he was approved as a district medical officer in Poland
where he discovered anthrax was endemic. His work on anthrax was presented and his papers
on the subject were published under the auspices of Ferdinand Cohn.
Koch, R. 1876. Untersuchungen ueber Bakterien V. Die Aetiologie der
Milzbrand-Krankheit, begruendent auf die Entwicklungsgeschichte des Bacillus Anthracis.
Beitr. z. Biol. D. Pflanzen 2: 277-310. In Milestones in Microbiology: 1556 to
1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p89 [PDF].
Jean Jacques Theophile Schloesing proves that nitrification
is a biological process in the soil by using chloroform vapors to inhibit the production
of nitrate. One of the greatest practical applications of this knowledge was in the
treatment of sewerage.
Schloesing, J. and A. Muntz. 1877. Sur la Nitrification par les Ferments
Organises. Comptes Rendus de lAcademie des Sciences, Paris, LXXXIV: 301-303.
Robert Koch dries films of bacteria, stains them with methylene blue
and then photographs them. He uses cover slips to prepare permanent visual records.
Koch, R. 1877. Verfahren zur Untersuchung, zum Conservieren und Photogaphiren
der Bakterien. Beitraege zur Biologie der Pflanzen. 2: 399-434
John Tyndall publishes his method for fractional sterilization and clarifies the
role of heat resistant factors (spores) in putrefaction. Tyndalls conclusion adds a
final footnote to the work of Pasteur and others in proving that spontaneous generation is
New Details Add to Our Understanding of Spontaneous Generation
Controversies, ASM News 63, 1997. p.193 [PDF]
Tyndall, J. 1877. On Heat as a Germicide when Discontinuously
Applied," Proceedings of the Royal Society of London. 25:569
Thomas Burrill demonstrates for the first time a bacterial
disease of plants; Micrococcus amylophorous causes pear blight.
Bacteria as the Cause of Disease in Plants: A Historical Perspective, ASM News
45, 1979. p.1 [PDF]
Burrill, Thomas Jonathan. 1878. Pear blight. Trans. Ill. State Hort. Soc.,
Joseph Lister publishes his study of lactic fermentation of
milk, demonstrating the specific cause of milk souring. His research is conducted using
the first method developed for isolating a pure culture of a bacterium, which he names Bacterium
Lister, J. 1878. On lactic fermentation and its bearing on pathology. Trans
Path. Soc., Lond. xxix: 425-67. In Milestones in Microbiology: 1556 to 1940,
translated and edited by Thomas D. Brock, ASM Press. 1998, p58 [PDF]
Serious attention to the trypanosomes of mammals was drawn by the work of Timothy
Lewis on the parasite of Indian rats (Trypanosoma lewisi), the importance of
which was realized after George Evans (1880) discovered the pathogenic trypanosome
in horses and camels in India (Trypanosoma evansi)
Lewis, T.R. (1878) "The microscopic organisms found in the blood of man and
animals and their relation to disease." Ann. Rpt. San. Commis. Govt. India, Calcutta
Lewis, T.R. (1879) "Flagellated organisms in the blood of healthy
rats." Quart. J. Micr. Sci. 19:109
Evans, G. "Report on the surra disease in the Dera Ismail Khan
District." Punjab Govt. Milit. Dept. No. 493:446
Albert Neisser identifies Neisseria gonorrhoeoe, the
pathogen that causes gonorrhea. He may be the first to attribute a chronic disease
to a microbe.
Neisser, A. 1879. Ueber eine der Gonorrhoe eigenthumliche Micrococcusform.
Vorlaufige Mitteilung. Cbl. F. d. Med. Wiss. 28: 497-500.
Louis Pasteur develops a method of attenuating a
virulent pathogen, the agent of chicken cholera, so it would immunize and not cause
disease. This is the conceptual break-though for establishing protection against disease
by the inoculation of a weakened strain of the causative agent. Pasteur uses the word
"attenuated" to mean weakened. As Pasteur acknowledged, the concept came from
Jenners success at smallpox vaccination.
Plasmids, Pasteur, and Anthrax, ASM News 49,1983. p.320 [PDF]
Pasteur, L. 1880. Sur les maladies virulentes et en particulier sur la maladie
appelee vulgairement cholera des poules. Compt. Rend. Acad. Sc. 90: 239-248.
Pasteur, L. 1880. De lattenuation du virus cholera des poules. Compte
rend. Acad. se. 91: 673-680 In Milestones in Microbiology: 1556 to 1940, translated
and edited by Thomas D. Brock, ASM Press. 1998, p126 [PDF]
C. L. Alphonse Laveran finds malarial parasites in erythrocytes of infected
individuals and shows that the parasite enters the organism and replicates. Laveran was
awarded the Noble Prize in Medicine and Physiology in 1907
1907 Nobel Prize
Laveran, A. 1880. A new parasite found in the blood of malarial patients.
Parasitic origin of malarial attacks. Bull. mem. soc. med. hosp. Paris. 17:
Koch struggles with the disadvantages of using liquid media for certain experiments.
He seeks out alternatives, and first uses an aseptically cut slice of a potato as a solid
culture medium. He also turns to gelatin, which is added to culture media; the resulting
mixture is poured onto flat glass plates and allowed to gel. The plate technique is used
to isolate pure cultures of bacteria from colonies growing on the surface of the plate.
Koch publishes his Methods for the Study of Pathogenic Organisms in which he
describes his success with solidified culture media.
Koch, R. 1881. Zur Untersuchung von pathogenen Organismen. Mitth. a. d. Kaiserl.
Gesundheitsampte 1: 1-48. In Milestones in Microbiology: 1556 to
1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p101 [PDF]
Paul Ehrlich refines the use of the dye methylene blue in bacteriological
staining and uses it to stain the tubercule bacillus. He shows the dye binds to the
bacterium and resists decoloration with an acid alcohol wash..
Ehrlich, P. 1881 Ueber das Methylenblau und seine klinisch-bakterioskopische
Verwerthung. Ztschr. f. klin. Med. ii: 710-713.
Ehrlich, P. 1882. Aus dem Verein fur innere Medicin zu Berlin. Deutsche
medizinische Wochenschrift 8:269-270 In Milestones in Microbiology: 1556 to 1940,
translated and edited by Thomas D. Brock, ASM Press. 1998, p118 [PDF]
Koch systematically investigated the efficacy of chemical disinfectants
demonstrating that carbolic acid used by Lister in aseptic surgery was merely
bacteriostatic and not bactericidal. He first recognized that disinfection depended on the
chemical concentration and contact time. Anthrax spores were dried on silk threads,
exposed to disinfectants, washed with sterile water and cultured to evaluate a range of
Koch, R. "Ueber Desinfection." Mittheilungen aus dem kaiserlichen
Gesundheitsamt 1:234-282, 1881
Angelina Fannie and Walther Hesse
in Koch?s laboratory use agar, an extract of algae, as a solidifying agent to prepare
solid media for growing microbes. Fannie suggests the use of agar-agar after leanring of
it from friends who cook. Agar replaces gelatin because it remains solid at temperatures
up to 100 degrees centigrade, it is clear, and it resists digestion by bacterial enzymes.
Walther and Angelina Hesse: Early Contributors to Bacteriology, ASM News 58,
1992. p.425 [PDF]
No formal article was published but see:
Hitchins, Arthur Parker and Morris C. Leikind, 1939. The Introduction of
Agar-Agar Into Bacteriology. Journal of Bacteriology. 37: 485-493.
Robert Koch also mentions the cultivation of bacteria in agar-agar in The
Aetiology of Tuberculosis. See below.
Robert Koch isolates the tubercule bacillus, Mycobacterium tuberculosis.
The search for the tubercule bacillus is more difficult that anthrax. He finally isolates
the bacillus from the tissues of a workman and stains them with methylene blue, yielding
blue colored rods with bends and curves. He injects the tissues from people who had died
into animals and then grows the bacilli he isolates into pure cultures.
Koch, R. 1882. Die Aetiologie der Tuberculose. Berl. Klin. Wchnschr., xix:
221-230. In Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas
D. Brock, ASM Press. 1998, p109 [PDF]
Edward Theodore Klebs and Fredrich Loeffler independently
discover Corynebacterium diphtheriae, which causes diphtheria. Loeffler later shows
that the bacterium secretes a soluble substance that affects organs beyond sites where
there is physical evidence of the organism.
Klebs, E. 1883. Ueber Diphtherie. Verh. D. Congresses f. Inn. Med., II.
Congr.Bergmann Weisbaden. 139-154.
Loeffler, F. 1884. Utersuchung uber die Bedeutung der Mikroorganismen fir die
Entstehung der Diptherie beim Menschen, bei der taube und beim Kalbe. Mitth. a. d.
kaiserl. Gesundheitsampte. Ii: 421-499.
Ulysse Gayon and Gabriel Dupetit isolate in pure culture two strains of
denitrifying bacteria. They show that individual organic compounds, such as sugars and
alcohols, can replace complex organics and serve as reductants for nitrate, as well as
serving as carbon sources.
1986: Centenary of the Isolation of Denitrifying Bacteria, ASM News 52, 1986.
Gayon, U., and G. Dupetit. 1883. La fermentation des nitrates. Mem. Soc. Sci.
Phys. Nat. Bordeaux Ser. 2. 5: 35-36.
Metchnikoff demonstrates that certain body cells move to damaged areas of the body
where they consume bacteria and other foreign particles. He calls the process
phagocytosis. He proposes a theory of cellular immunity. With Ehrlich, Metchnikoff is
awarded the Noble Prize in Medicine and Physiology in 1908
1908 Nobel Prize
Centennial of the Rise of Cellular Immunology: Discovery at Messina, ASM News
48, 1982. p.558 [PDF]
Metschnikoff, E. 1884. Ueber eine Sprosspilzkrankheit der Daphnien. Beitrag zur
Lehre uber den Kampf der Phagocyten gegen Krankheitserrenger, Archiv f. pathologische
Anatomie und Physiologie und f. klinische Medicin, 96: 177-195. In
Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas D. Brock, ASM
Press. 1998, p132 [PDF]
Robert Koch puts forth what will become his
best-known work, a set of postulates, or standards of proof involving the
tubercle bacillus. Koch's postulates are published in a work titled the The
Etiology of Tuberculosis. The paper includes a demonstration of three major facts: 1)
the presence of the tubercule bacillus (as proved by staining) in tubercular lesions of
various organs of humans and animals, 2) the cultivation of the organisms in pure culture
on blood serum, and 3) the production of tuberculosis at will by its inoculation into
guinea pigs. Koch was awarded the Nobel Prize in Medicine and Physiology in 1905
1905 Nobel Prize
The Etiology of Tuberculosis: A Tribute to Robert Koch on the Occasion of the
Centenary of His Discovery of the Tubercule Bacillus, ASM News 48, 1982. p.248 [PDF]
Preface to Brock's Robert Koch: A Life in Medicine and
Bacteriology by James Strick [PDF]
Koch, Robert. 1884. Die Aetiologie der Tuberkulose, Mittheilungen aus dem
Laiserlichen Gesundheitsampte. 2: 1-88. In Milestones in Microbiology: 1556 to
1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p116 [PDF]
Hans Christian J. Gram develops a dye system for identifying bacteria [the Gram
stain]. Bacteria which retain the violet dye are classified as gram-positive. The
distinction in staining is later correlated with other biochemical and morphological
Gram, C. 1884. Ueber die isolirte Farbung der Schizomyceten in Schitt-und
Trockenpreparaten, Fortschritte der Medicin, 2: 185-189. In Milestones in
Microbiology: 1556 to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998,
Together with Pasteur, the French firm Chamberlands Autoclave, develops a
chamber to sterilize materials using superheated steam.
Chamberland, C. 1884. Sur un filtre donnant de leau physiologiquement
pure. Compt. Rend. Acad. d. sc. Paris. xcix: 247.
As part of his rabies
research, Louis Pasteur oversees injections of the child Joseph Meister with
"aged" spinal cord allegedly infected with rabies virus. Pasteur uses the term
"virus" meaning poison, but has no idea of the nature of the causitive organism.
Although the treatment is successful, the experiment itself is an ethical violation of
research standards. Pasteur knew he was giving the child successively more dangerous
Pasteur: High Priest of Microbiology, ASM News 61, 1995. p.575 [PDF]
Pasteurs Dilemma: The Road Not Taken. ASM News vol. 40, 1974, p. 703 [PDF]
Preface to René Dubos' Pasteur and Modern Science
by Gerald L. Geison [PDF]
Pasteur, L. 1885. Methode pour prevenir la rage apres morsure, Compt rend. Acd.
Sc. 101: 765-773.
Paul Ehrlich espouses the theory that certain chemicals, such as dyes, affect
bacterial cells and reasoned that these chemicals could be toxic against microbes, work
that lays the foundation for his development of arsenic as a treatment for syphilis.
Ehrlich, P. 1885. Das Sauerstoff-Bedurfniss des Organismus, eine farbanalytische
Studie. Hirschwald, Berlin.
Theodor Escherich identifies a bacterium, that is a natural inhabitant of the
human gut, which he names Bacterium coli. He shows that certain strains are
responsible for infant diarrhea and gastroenteritis.
Escherich, T. 1885. Die Darmbakterien des Neugeborenen und Sauglings,
Fortschr.d. Med. 3: 515-522; 251-251,
Theobald Smith and D. E. Salmon inject heated killed whole
cell vaccine of hog cholera into pigeons and demonstrate immunity to subsequent
administration of a live microbial culture. The organism is a bacterium and unrelated to
hog cholera or swine plague disease, which is caused by a virus.
Salmon, D. E. and T. Smith. On a new method of producing immunity from
contagious diseases, Proceedings of the Biological Society, (Washington, D. C.) 3:
Sergei Winogradsky studies Beggiatoa and determines
that it can use inorganic H2S as an energy source and CO2 as a carbon source. He
establishes the concept of autotrophy and its relationship to natural cycles.
Winogradsky, S. 1887. Uber Schwefelbacterien. Botanische Zeitung. XLV:
Julius Richard Petri working in Kochs laboratory, introduces a new type of
culture dish for semi-solid media. The dish has an overhanging lid that keeps contaminants
Petri, R. J. 1887. Eine kleine Modification des Kochschen
Plattenverfahrens. Centralbl. F. Bakteriol., etc., 1: 279-280 In Milestones in
Microbiology: 1556 to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998,
The Institut Pasteur is founded in France in
Emile Roux and Alexandre Yersin show that Cornyebacterium diphtheriae
affects tissues and organs by a toxin. They use a filtrate from cells that can directly
kill laboratory animals.
From "Diphtheritic" Poison to Molecular Toxinology, ASM News 53, 1987.
Roux E. and A. Yersin. 1888. Contribution a letude de la diphtherie. Ann.
Inst. Pasteur 2: 629-661. 3: 273.
Martinus Beijerinck uses enrichment culture, minus
nitrogenous compounds, to obtain a pure culture of the root nodule bacterium Rhizobium,
demonstrating that enrichment culture creates the conditions for optimal growth of a
Early Biotechnology: The Delft Connection, ASM News 59, 1993. p.401 [PDF]
Beijerinck, M. 1888. Die Bakterien de Papilionaceenknollchen. Botanische
Zeitung, Vol. 46: 725-804. In Milestones in Microbiology: 1556 to 1940,
translated and edited by Thomas D. Brock, ASM Press. 1998, p220 [PDF]
Hellriegel and Wilfarth describe symbiotic nitrogen fixation by nodulated
legumes. Hellriegel first reported this to a scientific meeting in September 1886, and
published a somewhat more extensive paper a few weeks later. The 1888 publication with
Wilfarth is considered to be "the classical paper."
Hellriegel, H, and Wilfarth, H. "Untersuchungen uber die Stickstoffnahrung
der Gramineen und Leguminosen." Beilageheft zu der Zeitschrift des Vereins fur
Rubenzucker-Industrie Deutschen Reichs, 234 pp., 1888
A. Charrin and J. Roger discover that bacteria can be
agglutinated by serum.
Charrin, A. and J. Roger. 1889. Note sur le developpement des microbes pathogens
dans le serum des animaux vaccines. Soc. De Biol. 9e ser., I: 667-669.
Kitasato obtained the first pure culture of the strict anaerobic pathogen, the tetanus
bacillus Clostridium tetani. Taking advantage of the fact that the spores of the
organism are extremely heat-resistant, he heated a mixed culture of C. tetani and other
bacteria at 80 degrees for one hour, then cultivated them in a hydrogen atmosphere.
Kitasato, S. "Ueber den Tetanusbacillus." Ztschr. Hyg. u.
Infektionskrank. 7:225-234, 1889
Emil von Behring
and Shibasaburo Kitasato working together in Berlin in 1890 announce the discovery
of diphtheria antitoxin serum, the first rational approach to therapy of infectious
diseases. They inject a sublethal dose of diphtheria filtrate into animals and produce a
serum that is specifically capable of neutralizing the toxin. They then inject the
antitoxin serum into an uninfected animal to prevent a subsequent infection. Behring,
trained as a surgeon, was a researcher for Koch. Kitasato was Kochs first student at
the Institute of Hygiene. Behring was awarded the Nobel Prize in Medicine and Physiology
1901 Nobel Prize
Behring, E. 1890. Untersuchungen ueber das Zustandekommen der
Diphtherie-Immunitat bei Thieren. Dt. Med. Wochenschr. 16: 1145-1148. In
Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas D. Brock, ASM
Press. 1998, p141 [PDF]
Behring, E. and Kitasato, S. 1890. Ueber das Zustandekommen der
Diphtherie-Immunitat und der Tetanus-Immunitat bei thieren. Deutsche medizinsche
Wochenschrift 16:1113-1114 In Milestones in Microbiology: 1556 to 1940, translated
and edited by Thomas D. Brock, ASM Press. 1998, p138 [PDF]
Sergei Winogradsky succeeds in isolating
nitrifying bacteria from soil. During the period 1890-1891, Winogradsky performs the major
definitive work on the organisms responsible for the process of nitrification in nature.
Winogradsky, S. 1890. Recherches sur les Organismes de la Nitrification.
Computer Rendu Vol 110: 1013-1016 In Milestones in Microbiology:
1556 to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p231 [PDF]
proposes that antibodies are responsible for immunity. He shows that antibodies form
against the plant toxins ricin and abrin. With Metchnikoff,
Ehrlich is jointly awarded the Nobel Prize in Medicine and Physiology in 1908
1908 Nobel Prize
Ehrlich, P. 1891. Experimentelle Untersuchungen uber Immunitat, I. Ueber Ricin,
II. Ueber Abrin. Deutsche med. Wchnschr. xvii. 976, 1218.
publishes the first evidence of the filterability of a pathogenic agent, the virus of
tobacco mosaic disease, launching the field of virology. He passes the agent
through candle filters that retain bacteria but isn't sure that he has identified a new
When Did Virology Start, ASM News 62, 1996. p.142 [PDF]
Mosaic Virus and Its Contributions to Virology, ASM News 65, 1999.p.675
Ivanowski, D. I. 1892. On two diseases of tobacco. Sel. Khoz. Lesov. 169:108-121;
an English translation appears as an appendix to Hughes, S. S. (1972). The origins and
development of the concept of the virus in the late nineteenth century. Ph.D. thesis,
London University. (13; 25; 115)
William Welch and George Nuttall identify Clostridium perfringens, the
organism responsible for causing gangrene.
Welch W. H. and G. Nuttall. 1892. A gas-producing bacillus (b. aerogenes
capsulatus, nov.spec.) , capable of rapid development in the blood vessels after death.
Johns Hopkins Hosp. Bull. 3: 81-91.
Theobald Smith and F.L. Kilbourne establish
that ticks carry Babesia microti, which causes babesiosis in animals and humans.
This is the first account of a zoonotic disease and also the foundation of all later work
on the animal host and the arthropod vector.
Smith, T. and F. L. Kilbourne. 1893. Investigations into the nature, causation
and prevention of Texas or southern cattle fever. Bur. Anim. Ind. Bull. 1: 151-152.
Richard Pfeiffer observes that a heat stable toxic material
bound to the membrane of Vibrio Cholerae is released only after the cells are
disintegrated. He calls the material endotoxin, to distinguish it from filterable material
released by bacteria.
Pfeiffer, R. 1894. Weitere Untersuchungen ueber das Wesen der Choleraimmunitat
und ueber specifisch baktericide Processe. Ztschr. f. Hyg. u. Infektionskrankh. xviii:
Alexandre Yersin isolates Yersinia (Pasteurella) pestis, the organism
that is responsible for bubonic plague. Shibasaburo Kitasato also observes the
bacterium in cases of plague
Yersin, A. 1894. La peste bubonique a Hong Kong. C. r. Acad. Sci. 119:
Yersin, A. 1894. La peste bubonique a Hong Kong. Ann. Inst. Pasteur. 8:
Kitasato, S. 1894. The bacillus of bubonic plague. Lancet 2: 428-430.
Kitasato, S. 1894. Preliminary notice of the bacillus of bubonic plague.
Practitioner 53: 311.
Kitasato, S. 1894. Preliminary notice of the bacillus of bubonic plague. U. S.
Marine Hosp. Serv. P. 343.
Martinus Beijerinck isolates the first sulfate-reducing bacterium, Spirillum
desulfuricans (Desulfovibrio desulfuricans).
Beijerinck, M. 1894. Noty uber dur nacheveis vom protozoen und spirillum in
trinkwasser. Centralbl. f. Bakteriol. 15: 10-15
Sergei Winogradsky isolates the first free-living
nitrogen-fixing organism, Clostridum pasteurianum.
Winogradsky, S. 1895. Recherches sur lassimilation de lazote
libre de latmosphere par les microbes. Arch. d. Sci. Biol., Institut Imperial de
Medicine Experimentale, St. Petersburg, Vol. 4.
David Bruce describes in great detail the Tsetse fly disease (Nagana - means
loss of spirits, depression, in Zulu) in Zululand. He also describes the parasite
(drawings of tryp and of tsetse) and demonstrates transmission by infected blood or fly
Bruce, D. "Preliminary Report on the Tsetse-Fly Disease, or Nagana, in
Zululand." Durban: Bennett & David 1895.
Max Gruber and Herbert Durham extend the 1889 observation
of Charrin and Roger to show the agglutination of bacteria by serum is specific. This was
recognized as a new disease diagnostic tool.
Gruber, M. and H. E. Durham. 1896. Eine neue Methode zur raschen Erkennung des
Choleravibrio und des Typhusbacillus. Munchen. Med. Wchnschr. xliii: 285-286.
Paul Ehrlich proposes his "side-chain" theory of
immunity and develops standards for toxin and antitoxin.
Ehrlich, P. 1897. Zur Kenntniss der Antitoxinwirkung. Fortschr. d. Med. xv:
Edward Buchner helps launch the field of enzymology by publishing the first
evidence of a cell-free fermentation process using extracts isolated from yeast. This
discovery refutes Pasteurs claim that fermentation requires the repsence of live
cells. Buchner is awarded the Nobel Prize in Chemistry in 1907
1907 Nobel Prize
Buchner, E. 1897. Alkoholische Gahrung ohne Hefezellen. Berichte der Deutschen
Chemischen Gesellschaft, 30: 117-124. In Milestones in Microbiology: 1556 to
1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p65 [PDF]
Waldemar Haffkine produces immunity against the plague with killed organisms.
Waldemar Haffkine: Pioneer of Cholera Vaccine, ASM News 53, 1987. p.366 [PDF]
Haffkine, W. 1897. Remarks on the plague prophylactic fluid. Brit. Med. J. 1:
Almwroth Wright and David Sample develop an effective vaccine with killed cells
of Salmonella typhi to prevent typhoid fever.
Wright, A. E. and D. Sample. 1897. Remarks on vaccination against typhoid fever.
British Medical Journal. I: 256-259.
Friedrich Loeffler and Paul Frosch prove that
foot-and-mouth disease in livestock is caused by organisms tiny enough to pass through
bacteriological filters and too small to be seen through a light microscope.
Friedrich Loeffler and His History of Bacteriology, ASM News 48 1982, p.297 [PDF]
Loeffler, F. and P. Frosch. 1898. Berichte der Kommission zur Erforschung der
Maul-und Klauenseuche bei dem Institut fur Infektionskrankheiten. Part I, 23:
371-391.In Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas D.
Brock, ASM Press. 1998, p149 [PDF]
Jules Bordet discovers that hemolytic sera acts on foreign blood in a manner
similar to the action of antimicrobic sera on microbes by precipitating the material from
solution. He shows there are two factors, a heat-labile substance found in normal blood
and a bacteriocidal material present in the blood of immunized animals.Bordet is awarded
the Nobel Prize in medicine and Physiology in 1919
1919 Nobel Prize
Bordet, J. 1898. Sur lagglutination et la dissolution des globules rouges
par le serum danimaux injectes de sang defibrine. Ann. De lInst. Pasteur. xii:
B. R. Schenck presents the first unequivocal case of sporotrichosis and includes
a description of the organism that was first isolated from the patient. This organism was
later named Sporotrichum schenckii.
Schenk, B. R. 1898. On refractory subcutaneous abscesses caused by a fungus
possibly related to the sporotricha. Johns Hopkins Hosp. Bull. 9: 286-290.
Ronald Ross shows that the malarial parasite undergoes a
cycle of development in mosquitoes and that the disease is transmitted by the bite of
female mosquitoes. Ross was awarded the Noble Prize in Medicine and Physiology in 1902
1902 Nobel Prize
Ross, R. 1899. Mosquitoes and malaria. Brit. Med. J., 432-433.
Martinus Beijerinck recognizes "soluble"
living microbes, a term he applies to the discovery of tobacco mosaic virus. A filtrate
free of bacteria retains ability to cause disease in plants even after repeated
dilutions.In 1897 he had pressed the juice from tobacco leaves infected with tobacco
mosaic disease, which gave the leaves a mottled appearance.
Martinus Beijerinck (1851-1931), ASM News 62, 1996. p.539 [PDF]
Beijerinck, M. 1899. Ueber ein Contagium vivum fluidum als Ursache der
Fleckenkrankheit der Tabaksblatter. Centralblatt fur bacteriologie und Parasirenkunde,
Part II, 5: 27-33. In Milestones in Microbiology: 1556 to 1940, translated and
edited by Thomas D. Brock, ASM Press. 1998, p153 [PDF]
The organizing meeting of the Society of American
Bacteriologists is held at Yale, December 28, 1899. The Society is the first
independent organization devoted to the promotion and service of bacteriology in the
United States. It later becomes the American Society for Microbiology.
There was no formal published paper but see: Conn, H.J. 1948. Professor Herbert
William Conn and the founding of the American Society of American Bacteriologists. Bact.
Reviews. 12: 275-296.
Abstracts of the first meeting were published in SCIENCE N.S. Vol. XI,
No. 273: 455-463, 1900
A Century of
Society Meetings, ASM News 65, 1999. p.296
by "Lost Souls" Among Naturalists, ASM News, 65 1999.p.266
Based on work of Walter
Reed, it is demonstrated that Yellow Fever is caused by a filterable
virus transmitted by mosquitoes. The agent is similar to that reported in 1898 by
Loffler and Frosch for foot and mouth disease of cattle. This is the first report
of a viral agent known to cause human disease. Based on the findings of the Yellow Fever
Commission the mosquito was eradicated.
No account was published immediately, but the papers of the Yellow Fever
Commission were published in 1911.
Reed, W. 1911. Papers by various authors of the Yellow Fever Commission. Sen.
Doc. 822. Washington, D. C.
W. Ophuls and H. C. Moffitt correctly identify the etiologic agent of
coccidioidomycosis, Coccidiodes immitis, as a mold. This was formerly described as
Ophuls, W. and H. Moffitt. 1900. A new pathogenic mould. Philadelphia Med. J. 5:
Jules Bordet and Octave Gengou develop the complement
fixation test. They show that any antigen-antibody reaction leads to the binding of
complement to the target antigen.
Bordet, J. and O. Gengou. 1901. Sur lexistencede substances
sensibilisatrices dans la plupart des serums antimicrobiens. Ann. De lInst. Pasteur.
E. Wildiers publishes the first description of a microbial growth factor,
opening the field of vitamin research. He finds that a water soluble extract of yeast has
a compund that is required for the growth of yeast. The material is later found to be a B
Wildiers, E. 1901. A new substance indispensable to the development of yeast. La
Cellule. 18: 313-332. In Milestones in Microbiology: 1556 to 1940, translated
and edited by Thomas D. Brock, ASM Press. 1998, p240 [PDF]
William Leishman observes Leishmania
donovani in the spleen of a soldier who dies from Dum-Dum fever. Charles Donovan
helps to identify the protozoan causing the disease.
Leishman, W. B. 1903. On the possibility of the occurrence of trypanosomiasis
in India. Br. Med. J. i: 1252-1254.
Donovan, C. 1903. On the possibility of the occurrence of trypanosomiasis in
India. Br. Med. J. ii: 79.
F. G. Novy cultivates trypanosomes isolated in the blood of rats.
Novy, F. G. and W. J. MacNeal. 1903. On the cultivation of Trypanosoma lewisi.
Contributions to Medical Research, Ann Arbor: George Wahr. 549-577.
Martinus Beijerinck obtains the first pure culture of
sulfur-oxidizing bacterium, Thiobacillus denitrificans. Under anaerobic conditions
it uses carbon dioxide as a source of carbon.
Beijerinck, M. 1904. Phenomenes de reduction produits par les microbes. Arch.
Neerl. (section 2) 9: 131-157.
Cornelius Johan Koning suggests that fungi play an important role in the
decomposition of organic matter and the formation of humus.
Koning, C. J. 1904. Beitrage zur kenntnis des lebens dur humuspilze und der
chemischen vorgange bei der humusbildung. Arch. Neerland. Sci. Exact. Et Nat. 9:34-107.
Franz Schardinger isolates aerobic bacilli which produce
acetone, ethanol, and acetic acid. These are important industrial chemicals.
Schardinger, F. 1904. Bacillus macerans. Centralblatt f. Backteriologie, II XIV:
Fritz R. Schaudinn and Erich Hoffman identify Treponema pallidum, the
cause of syphilis. The bacterium is isolated from fluid leaking from a syphylitic chancre
and is spiral in appearance.
Metchnikoff and Syphilis Research during a Decade of Discovery, ASM News 62,
1966. p.307 [PDF]
Schaudinn, F. R. and E. Hoffman. 1905. Uber Spirochatenbefunde in
Lymphdrusensaft Syphilitischer. Dtsch. med. Wschr. 31: 711.
Shigetane Ishiwata discovers that the cause of a disease outbreak in silkworms
is a new species of bacteria, later called Bacillus thuringiensis, or Bt. Ishiwata
called the organism "Sotto-Bacillen." ("Sotto" in Japanese signifies
Ishiwata, S. 1905. Concerning "Sotto-Kin" a bacillus of a
disease of the silkworm. Rept. Assoc. Seric. Japan. Pp. 160-161.
Sir Roland Biffen shows that the ability of wheat to resist infection with a fungus
is genetically inherited.
Biffen, R.H. 1905 Experiments with wheat and barley hybrids,
illustrating Mendels Laws of heredity. J. Roy. Agric. Soc. 65:337-45
August von Wasserman describes the "Wasserman
reaction" for the diagnosis of syphilis in monkeys. The test uses complement fixation
and becomes the basis for the general uses of complement tests as diagnostics.
Wasserman, A., Neisser, A., and C. Bruck. 1906. Eine serodiagnostische reaktion
bei syphilis. Deutsche med. Wchnschr xxxii: 745.
N. L. Sohngen presents groundbreaking work on methane-using and
methane-producing bacteria. This is the first proof that methane can serve as an energy
and carbon source.
Sohngen, N. L. 1906. Ueber Bakterien, welche Methan als Kohlenstoffnahrung and
energiequelle gebrauchen. Zentralbl. Bakteriol. Parasitik. Abt. I. 15: 513-517.
A newly appointed pathologist in the Panama Canal Zone, Samuel Darling, performs
an autopsy on a patient with a disease resembling tuberculosis and an agent resembling Leishmania
sp. He recognizes significant differences between the etiologic agent and Leishmania
sp., and names the organism Histoplasma capsulatum, believing that it is a
protozoan. It is now known to be a fungus.
Darling, S. T. 1906. A protozoan general infection producing pseudo tubercules
in the lungs and focal necroses in the liver, spleen, and lymph nodes. JAMA. 46:
1283-1285. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM
Press. 1999, p.4 [PDF]
Erwin Smith and C.O. Townsend discover
that the cause of crown galls is a bacterium called Agrobacterium tumefaciens.
Smith, Erwin, and C.O.1907. Townsend. A plant tumour of bacterial
origin. Science 25: 671-673
Howard Ricketts shows that Rocky Mountain spotted fever is
caused by an organism that is intermediate in size between an virus and a bacterium. This
organism, Rickettsia, is transmitted by ticks. Ricketts dies from typhus, another
rickettsial disease, in 1910.
Ricketts, H. 1909. A micro-organism which apparently has a specific relationship
to Rocky Mountain spotted fever. J. Am. Med. Soc. 52: 379-380. In Microbiology: A
Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.8 [PDF]
Sigurd Orla-Jensen proposes that physiological characteristics of bacteria are
of primary importance in their classification. A primary example is a monograph he later
publishes on lactic acid bacteria that establishes the criteria for assignment.
Orla-Jensen, S. 1909. Die Hauptlinien des Naturlichen Bakterien-Systems.
Centralblatt fur Bakteriologie. Section 2, XXII: 305-346.
Carlos Chagas discovers the trypanosome, which he named Trypanosoma
cruzi, and its mode of transmission, via reduviid bugs, as the cause of the human
disease named for him.
Chagas, C. "Ueber eine neue Trypanosomiasis des Menschen." Mem.
Inst. Oswaldo Cruz 1:158-218
Charles Henry Nicolle demonstrates that typhus fever is
transmitted from person to person by the body louse. This information was used in both
world wars to reduce the incidence of typhus. Nicolle is awarded the Noble Prize in
Medicine and Physiology in 1928
1928 Nobel Prize
Nicolle, C. H., C. Compte, and E. Conseil. 1910. Experimental Transmission of
Exanthematous Typhus by body lice (Pediculus vestimenti). Ann. Past. Inst. 24:
Raimond Sabouraud summarizes about twenty years of his systematic and scientific
studies of dermatophytes and dermatophytoses in a classic treatise, Les Teinges. He
introduces a medium for the growth of pathogenic fungi.
Sabouraud, R. 1910. Maladies du Cuir Chevelu III. Maladies Cryptogamiques. Les
Teinges. Masson et Cie.
Rous discovers a virus that can cause cancer in chickens by injecting a cell free
filtrate of tumors. This is the first experimental proof of an infectious etiologic agent
of cancer. In 1909 a farmer brought Rous a hen that had a breast tumor. Rous performed an
autopsy, extracted tumor cells and injected them in other hens, where sarcoma developed.
Rous is awarded the Noble Prize in Medicine and Physiology in 1966
1966 Nobel Prize
Rous, Peyton. 1911. Transmission of a malignant growth by means of a cell free
filtrate. JAMA. 56: 198.
Rous, Peyton. 1911. A sarcoma of the fowl transmissable by an agent separable
from the tumor cells. J. Ex. Med. 13:397-411
announces the discovery of an effective cure (Salvarsan) for syphilis, the first specific
chemotherapeutic agent for a bacterial disease. Ehrlich was a researcher in Kochs
lab, where he worked on immunology. In 1906 he became head of the Research Institute for
Chemotherapy. He sought an arsenic derivative. The 606th compound worked. He
brought news of the treatment to London, where Fleming became one of the few physicians to
Ehrlich, P. 1912. Ueber Laboratoriumsversuche und klinische Erprobung von
Heilstoffen. Chem. Ztg. 36: 637-638.
discovery of bacteriophage, by Frederick Twort. Tworts discovery was
something of an accident. He had spent several years growing viruses and noticed that the
bacteria infecting his plates became transparent.
Twort, F. 1915. An investigation on the nature of ultra-microscopic viruses.
Lancet, 2: 1241-1243.
Chaim Weizmann, using the knowledge of Pasteurs discovery that yeast
ferments sugar, uses Clostridium acetobutylicum to produce acetone and butyl
alcohol. These were essential to the British munitions program during World War I.
Weizmann, C. 1915. British patent, 845.
McCrady establishes a quantitative approach for analyzing water samples for
coliforms using the most probable number, multiple-tube fermentation test. The test is
based on the ability of coliforms to grow in selective broth at 35=F8C producing acid or
gas within 24 to 48 hours. The number of coliforms and the 95% confidence limit can be
determined using MPN tables for the volumes and number of fermentation tubes used
McCrady, M.H. "The Numerical Interpretation of Fermentation Tube
Results." J. Infect. Dis. 17:183
Felix d'Herrelle independently describes bacterial viruses
and coins the name "bacteriophage."
Felix dHerrelle: His Life and Work and the Foundation of a Bacteriophage
Reference Center, ASM News 48, 1982. p.297 [PDF]
DHerrelle, F. 1917. Sur un microbe invisible antagoniste des bacilles
dysenteriques. Comp. rend. Acad. Sci. 165: 373-375.In Milestones in Microbiology:
1556 to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p157 [PDF]
J. N. Currie discovers how to produce citric acid in large quantities from the
mold Aspergillus niger-by employing a growth limiting medium rich in iron.
Currie, J. N. 1917. The citric acid fermentation of Asperigillus niger.
J. Bio. Chem. 31: 15-37.
Alice Evans establishes that members of
the genus Brucella. are responsible for the diseases of Malta Fever, cattle
abortion, and swine abortion. She reports that the bacteria are bacilli and not
Evans, A. 1918. Further studies on Bacterium abortus and related
bacteria. II. A comparison of Bacterium abortus with Bacterium bronchisepticus
and with the organism that causes Malta Fever . J. Infect. Dis. 22: 580-593.
Theobald Smith and M. S. Taylor describe the
microbe, Vibrio fetus n. sp., responsible for fetal membrane disease in cattle.
Smith and His Presidential Address to the Society of American Bacteriologists,
ASM News 47, 1981, p.231 [PDF]
Theobald Smith, 1859-1934: A Fiftieth Anniversary Tribute, ASM News 50, 1984.
Smith, T. and M. S. Taylor. 1919. Some morphological and biological characters
of the Spirilla (Vibrio fetus, n. sp.) associated with the disease of the
fetal membranes in cattle. J. Exp. Med. 30: 299-311.
James Brown uses blood agar as a medium to study the hemolytic reactions for the
genus Streptococcus and divides it into three types, alpha, beta, and gamma.
Brown, J.H. 1919. The use of blood agar for the study of streptococci.
Rockefeller Institute for Medical Research Monograph No.9. The Rockefeler Institute for
Medical Research, New York.
The SAB committee presents a report on the
Characterization and classification of Bacterial Types that becomes the basis for the
classic work of D. H. Bergey, later published in 1923.
Michael Heidelberger and O. A. Avery show that
carbohydrates from the pneumococcus can serve as virulence antigens and are serologically
specific. This overturns the current wisdom that only proteins or glycoproteins are
Heidelberger, M. and O. T. Avery. 1923. The soluble specific substances
of pnuemococcus, J. Exp. Med. 38: 73-79.
George and Gladys Dick describe the "Dick
test", a skin test for scarlet fever. They purify a soluble extoxin from hemolytic Streptococccus
pyogenes and use it as a diagnostic. They use Kochs postulates to show that
scarlet fever is caused by streptocoocci, recover the bacteria from all cases of the
disease and infect others with cultures of the bacterium.
Dick, G. and G. Dick. 1924. A skin test for susceptibility to scarlet fever.
JAMA. 82: 265-266.
Albert Calmette and Camille Guerin introduce a living non-virulent strain
of tuberculosis (BCG) to immunize against the disease. This is the result of work begun in
1906 on attenuating a strain of bovine tuberculosis bacillus. More than 200 subcultures
were grown before the resulting strain was tested.
Calmette, A. and C. Guerin. 1924. Vaccination of bovines against tuberculosis.
Ann. Inst. Pasteur. 38: 371-398.
Albert Jan Kluyver publishes an article "Unity and Diversity in the
Metabolism of Micro-organisms" that demonstrates common metabolic events occur in
different microbes. The processes he refers to are oxidation, fermentation and
biosynthesis. Klyuver also points out that life on earth without microbes would not be
Klyuver, A. J. 1924. Eenheid en verscheidenheid in de stofwisseling der
microben. Chem. Weekbl. 21, 266-80. In Microbiology: A Centenary Perspective,
edited by Wolfgang K. Joklik, ASM Press. 1999, p.188 [PDF]
and also In Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas D.
Brock, ASM Press. 1998, p247 [PDF]
Thomas Rivers distinguishes between bacteria and viruses,
establishing virology as a separate area of study. This paper was published after
he presented it at an SAB meeting held in December of 1926.
Rivers, T. 1927. Filterable viruses. A critical review. J. Bact. 14: 217.
Albert Jan Kluyver and Hendrick Jean Louis Donker propose
a universal model for metabolic events in cells based on a transfer of hydrogen atoms. The
model applies to aerobic and anaerobic organisms.
Kluyver, A. J. and H. J. L. Donker. 1926. Die einheit in der biochemie. Chem.
Zelle Geweke. 13: 134-190.
Everitt Murray isolates from rabbits a bacterium that is responsible for
listeriosis in man. The organism can grow at low temperatures and frequently is found in
food. He names it Bacterium monocytogenes. It is later renamed Listeria
Murray, E.G.D., R. A. Webb, and M.B.R. Swann. 1926. A disease of rabbits
characterized by a large mononuclear leucocytosis, caused by a hitherto undescribed
bacillus Bacterium monocytogenes. J. Pathol. Bacteriol. 29:407-39
discovers transformation in bacteria and establishes the foundation of molecular genetics.
He shows that injecting mice with a mixture of live, avirulent, rough Streptococcus
pneumoniae Type I and heat-killed, virulent smooth S. pneumoniae Type II, leads
to the death of the mice. Live, virulent, smooth S. pneumoniae Type II are isolated
from the dead mice. Not until the 1930s, did Avery, Macleod and McCarty take up
Griffiths work and try to explain the results.
Griffith, F. 1928. The significance of pneumococcal types. J. Hyg. 27,
Alexander Fleming publishes the first paper
describing penicillin and its effect on gram positive microorganisms. This finding
is unique since it is a rare example of bacterial lysis and not just microbial antagonism
brought on by the mold Penicillium. Fleming kept his cultures 2-3 weeks before
discarding them. When he looked at one set he noticed that the staphylococcus bacteria
seemed to be dissolving. The mold that contaminated the culture was a rare organism called
penicillium. He left the culture on the lab bench and went on vacation. While he was away
the culture was subjected to a cold spell followed by a warm one the only
conditions under which the discovery could be made. When penicillin is finally produced in
major quantities in the 1940s, its power and availability effectively launch the "Antibiotics
Era," a major revolution in public health and medicine. With Florey and Chain,
Fleming is awarded the Noble prize in Medicine and Physiology in 1945
1945 Nobel Prize
Fleming, A. 1929. On the antibacterial action of cultures of a Penicillium, with
a special reference to their use in the isolation of B. influenze. Brit. J. Exp.
Path. 10: 226-236. In Microbiology: A Centenary Perspective, edited by Wolfgang K.
Joklik, ASM Press. 1999, p.98 [PDF]
and also In Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas D.
Brock, ASM Press. 1998, p185 [PDF]
In Praise of
Antibiotics, ASM News 65, 1999. p.304
Henning Karstrom begins to identify the phenomena of enzyme
adaptation and of constitutive synthesis, in which synthesis of an enzyme either is
increased in response to the presence of the substrate of the environment or is
independent of the growth medium. His work is based on studies of carbohydrate metabolism
in Gram negative enteric bacteria.
Karstrom, H. 1930. .Ann. Ueber die enzymbildung in Bakterien. Thesis,
Rene Dubos working with Oswald Avery discovers Bacillus
brevis, an organism that breaks down the capsular polysaccharide of Type III S.
pneumocci and protects mice against pneumonia.
Dubos, R. and O. T. Avery. 1931. Decomposition of the capsular polysaccharide of
pneumonococcus type III by a bacterial enzyme. J. Exper. Med. 54: 51-71.
C. B. van Niel shows that photosynthetic bacteria
use reduced compounds as electron donors without producing oxygen. Sulfur bacteria use H2S
as a source of electrons for the fixation of carbon dioxide. He posits that plants use
water as a source and release oxygen.At this time Van Niel begins the first independent
?general microbiology? course at the Hopkins Marine Station in Pacific Grove, California.
van Niel Remembered, ASM News 53, 1987. p.75 [PDF]
van Neil, C. B. 1931. On the morphology and physiology of the purple and green
sulfur bacteria. Arch. Mikrobiol. 3: 1-112.
Margaret Pittman identifies variation, such as encapsulated forms, and type
specificity, such as type b, of the Haemophilus influenzae as determinants of
Pittman, M. 1931. Variation and type specificity in the bacterial species Haemophilus
influenzae. J. Exp. Med. 53: 471-492.
William Joseph Elford discovers that viruses range in size from large protein
molecules to tiny bacteria.
Elford, W. J. 1931. A new series of graded colloidal membranes suitable for
general bacteriological use, especially in filterable virus studies. J. Pathol Bacteriol. 34:
Alice Woodruff and Ernest Goodpasture devise a technique of cultivating
viruses in eggs.
Woodruff, A. and E. Goodpasture. 1931. The susceptibility of the
chorio-allantoic membrane of chick embryos to infection with the fowl-pox virus. Am. J.
Path. 7: 209-222.
R. Stewart and K. Meyer describe
the isolation of Coccidiodes immitis from soil located near where several patients
were thought to have become infected. This establishes that the soil is a reservoir for
Stewart, R. A. and K. F. Meyer. 1932. Isolation of Coccidiodes immitis
(Stiles) from the soil. Proc. Soc. Exper. Biol. & Med. 29: 937-938.
Rebecca Lancefield describes a method of producing
streptococcal antigens and sera for use in precipitin tests and suggests that this
approach can be used epidemiologically to identify the probable origin of a given strain.
Rebecca Craighill Lancefield, Pioneer Microbiologist, ASM News. 41,1975. p.805 [PDF]
Lancefield, R. C. 1933. A serological differentiation of human and other groups
of hemolytic streptococci. J. Exper. Med. 57: 571-595.
Ladislaus Laszlo Marton is the first to examine biological
specimans with the electron microscope, which achieves magnifications of 200-300, 000x.
Later in 1937, he publishes the first electron micrographs of bacteria.
Marton, L. 1934. La microscopie electronique des onjectes biologiques. Bull.
Acad. Belg. Cl. Sci. 20: 439-466.
Alice Evans accomplishes the first typing of a strain of bacteria with
Evans, A. 1934. Streptococcus bacteriophage: A study of four serological types.
Public Health Rep. 49: 1386-1401.
William de Monbreun describes the dimorphic nature of Histoplasma capsulatum after
being surprised by the growth of a mold from patient tissues displaying yeasts.
de Monbreun, W. A. 1934. The cultivation and cultural characteristics of
Darlings Histoplasma capsulatum. Am. Jour. Trop. Med. 14: 93-125.
Gerhard J. Domagk uses
a chemically synthesized antimetabolite, Prontosil, to kill Streptococcus in mice.
It is later shown that Prontosil is hydrolyzed in vivo to an active compound,
sulfanilamide. One of the first patients to be treated with Protonsil was Domagks
daughter who had a streptococcal infection that was unresponsive to other treatments. When
she was near death, she was injected with large quantities of Protonsil and she made a
dramatic recovery. Domagk is awarded the Nobel Prize in Medicine and Physiology in 1939
1939 Nobel Prize
Domagk, G. J. 1935. Ein Beitrag zur Chemotherapie der bakteriellen infektionen.
Dtsch. med. Wochenschr. 61: 250-253. In Milestones in Microbiology: 1556 to
1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p195 [PDF]
Wendell Stanley crystallizes tobacco mosaic virus and shows it
remains infectious. However, he does not recognize that the infectious material is nucleic
acid and not protein. Together with Northrop and Sumner, Stanley is awarded the Nobel
Prize in Chemistry in 1946
1946 Nobel Prize
Stanley, W. 1935. Isolation of a crystalline protein possessing the properties
of tobacco-mosaic virus. Science. 81: 644-654.In Milestones in Microbiology: 1556
to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p160 [PDF]
William A. Hinton, chief of the Wasserman laboratory at Harvard, publishes the
first major text on syphilis, Syphilis and its Treatment, which includes reference
to the Davies-Hinton test to detect syphilis in spinal fluids.
J. D. Bernal, F. C. Bauden, N. W, Pirie, and I. Pankuchen
demonstrate that isolated preparations of tobacco mosaic virus contain phosphorus as a
component of a phospho-ribonucleic acid. They also isolate ribonucleic acids.this
challenges the claim by Stanley that the TMV is composed only of protein
Bauden, F. C. , N. W. Pirie, J. D. Bernal, and I. Fankuchen. 1936. Liquid
crystalline substances from virus infected plants. Nature 138:1051-1052.
Harland Wood and Chester Werkman show that CO2 is consumed by Propionibacterium
arabinosum duirng the fermentation of glycerol. This is the first report of carbon
dioxide fixation by a heterotrophic bacterium.
H.G. Wood and C.H. Werkman. 1936. The utilization of CO2 in the dissimilation of
glycerol by propionic acid bacteria. Biochem. J. 30:48-53. In Microbiology: A Centenary
Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.202 [PDF]
Field tests of Max Theilers vaccine against
yellow fever prove successful. The vaccine is based on a mouse passaged virus. The
Rockefeller Foundation manufactures more than 28 million doses by 1947. Theiler was
awarded the Nobel Prize in Medicine and Physiology in 1951
1951 Nobel Prize
Theiler, M. and H. H. Smith. 1937. J. Exp. Med. 65: 787.
Smith, H. H., H. A Penna, and A. Paoliello. 1938. Yellow fever vaccination with
cultured virus (17D) without immune serum. Am. J. Trop. Med. 18: 437-468.
E. L. Ellis and Max Delbruck establish the concept of the
one-step viral growth cycle for a bacteriophage active against E. coli.
E.L Ellis and M.L. Delbruck. 1939. The growth of
bacteriophage.J.Gen.Physiol. 22:36584. In Microbiology: A Centenary Perspective, edited by
Wolfgang K. Joklik, ASM Press. 1999, p448 [PDF]
Pathologist Howard Florey and biochemist Ernest
Chain produce an extract of penicillin, the first powerful antibiotic. They
isolate the antibiotic from Flemings mold cultures and demonstrate that it can cure
infections in animals. Florey and Chain began their research by focusing on the discovery
by Fleming of lysozyme. In the course of reviewing Flemings papers, Chain read the
description of penicillin. With Fleming, Florey and Chain are awarded the Nobel Prize in
Medicine and Physiology in 1945
1945 Nobel Prize
Chain, E., H. W. Florey, A. D. Gardner, N. G. Heatley, M. A. Jennings, J.
Orr-Ewing, and A. G. Sanders Penicillin as a chemotherapeutic agent. Lancet 2:
226-228. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM
Press. 1999, p.112 [PDF]
Ernest Chain and E.P. Abraham describe a sustance from E. coli
that can inactivate penicillin. It was the first bacterial product that was recognized to
mediate resistance to an antibacterial agent.
Abraham, E.P. and E. Chain. 1940. An enzyme from bacteria able to destroy
penicillin. Nature 3713:837. In Microbiology: A Centenary Perspective, edited by Wolfgang
K. Joklik, ASM Press. 1999, p.115 [PDF]
Helmuth Ruska uses an electron microscope to obtain the first pictures of a
Ruska, H. 1940. Die Sichtbarmachung der BakteriophagenLyse im Ubermikroskop.
Naturwissenschaaften. 28: 45-6.
Charles E. Smith and his colleagues demonstrate the usefulness of a
tuberculin-like preparation of Coccidiodes immitis in detecting prior exposure to
the fungus. This preparation allowed for the delineation of the endemic area for the
Smith C. E. 1940. Epidemiology of acute coccidioidomycosis with erythema
nodoosum ("San Joaquin" or "Valley Fever"). Am. Jour. Pub. Health 30:
Donald O. Woods describes the relation of para-aminobenzoic acid to the
mechanism of action of sulfanilamide, which was used by Domagk to treat Streptococcal infections
Woods, D. O. 1940. The relation of p-aminobenzoic acid to the mechanism of the
action of sulphanilamide. Brit. J. Exp. Path. 21: 74-90. In Milestones in
Microbiology: 1556 to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998,
Selman Waksman and H. Boyd Woodruff discover actinomycin, the first
antibiotic obtained pure from an actinomycete, leading to the discovery of many other
antibiotics from that group of microorganisms. After Renee Dubos discovered two
antibacterial substances in soil, Waksman decided to focus on the medicinal uses of
antibacterial soil microbes.
Waksman, S. and H. B. Woodruff. 1940. Bacteriostatic and bactericidal substances
produced by soil Actinomyces. Proc. Soc. Explt. Biol. Med. 45: 609-614.
and Edward Tatum jointly publish a paper on their experiments using the fungus Neurospora
crassa to establish that particular genes are expressed through the action of
correspondingly specific enzymes. The first gene to be identified controlled the synthesis
of an enzyme in a series that led to generation of niacin. This report is the genesis
of the "one gene-one enzyme" concept. They chose Neurospora because it grew
and reproduces quickly. They grew Neurospora on a culture medium that contained nutrients
essential to its growth and then irradiated the colonies with x-rays. Some colonies that
grew but failed to thrive. Only after adding vitamin B6 did the irradiated organisms begin
to grow normally. By mating the defective organisms with normal organisms they showed the
defect was inherited as a Mendelian recessive gene. With Lederberg, Beadle and Tatum are
awarded the Nobel Prize in Medicine and Physiology in 1958
1958 Nobel Prize
Beadle, G. and E. Tatum. 1941. Genetic control of biochemical reactions in
Neurospora. Proc. Nat. Acad. Sci. 27: 499-506. In Microbiology: A Centenary
Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.308 [PDF]
Charles Fletcher first demonstrates that penicillin is non-toxic to
human volunteers, by injecting a police officer suffering with a lethal infection.
Abraham, E. P., E. Chain, C. M. Fletcher, A. D. Gardner, N. G. Heatley, M. A.
Jennings, and H. W. Florey. 1941. Further observations on penicillin. Lancet 2:
McFarlane Burnet proposes that descendents of antigen reacting cells produce
antibodies specific to the antigen.
Burnet, F. M., M. Freeman, A. Y. Jackson and D. Lush. 1941. The Production of
antibodies. (Monographs of the Walton and Eliza Hall Institute No. 1.) London: Macmillan
& Co. Ltd.
George Hirst demonstrates that influenza virus agglutinates red blood cells.
Since the cell attachment proteins of most viruses also agglutinate red blood cells, this
property provides a rapid, accurate and quantitative method of counting virus particles.
Hirst, G.K. 1941. The agglutination of red blood cells by allantoic fluid chick
embryos infected with influenza virus. Science. 94:22-23
Selman Waksman suggests the word "antibiotic"
(coined in 1889 by P. Vuillemin) after Dr. J. E. Flynn, the editor of Biological Abstracts
asked him to suggest a term for chemical substances, including compounds and preparations
that are produced by microbes and have antimicrobial properties.
Although there is no journal citation, Waksman recalled the incident in his book The
Antibiotic Era. Because the word was accepted quickly and the meaning became confused,
Waksman published a comprehensive definition in 1947: "an antibiotic is a chemical
substance produced by microbes that inhibits the growth of and even destroys other
microbes (and is active in dilute solutions)" was added later.
Albert H. Coons, H.J. Creech, R.N. Jones, and E. Berliner use a fluorescent
antibody to find antigens of pneumococci in human tissue. They chemically bind a
fluorescent group to antipneumococcus type III antibody and use a fluorescence microscope
to locate the antibody in histologic sections. They also provided some basic data on
sensitivity and specificity.
A.H. Coons, H.J. Creech, R.N. Jones, and E. Berliner. Demonstration of
pneumoccocal antigen in tissues by use of fluorescent antibody. 1942 J. Immunol.
45:159-70. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM
Press. 1999,p.12 [PDF]
Thomas Anderson and Salvador Luria photograph bacteriophages with the aid of an
electron microscope, confirming earlier work by Ruska. They demonstrate that an E. coli
T2 phage has a head and a tail.
Luria, S. E. and T. F. Anderson. 1942. The identification and characterization
of bacteriophages with the electron microscope. Proc. Natl. Acad. Sci. USA. 28:
Jules Freund and Katherine McDermott identify adjuvants, such as paraffin
oil, that can significantly boost antibody production. The preparation is composed of heat
killed tubercule bacilli in a water-in-oil emulsion.
Freund, J. and K. McDermott. 1942. Sensitization to horse serum by means of
adjuvants. Proceedings of the Society for Experimental Biology and Medicine 49:
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 and Physiology in 1969
1969 Nobel Prize
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
Hungate, R. E. 1943. Further experiments on cellulose digestion by the protozoa
in the rumen of cattle. Biol. Bull. 84: 157-163.
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 Averys 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.
Oswald T. Avery Collection
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 and Physiology in 1952
1952 Nobel Prize
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.
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 and Physiology in 1969
1969 Nobel Prize
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.
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.
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
Mary Shorbs 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.
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 and Physiology in 1954
1954 Nobel Prize
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:
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.
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:
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 and Physiology in 1965
1965 Nobel Prize
Genetics at the Institute Pasteur: Substance and Style, ASM News 53, 1987. p.547
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,
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 and Physiology in
1958 Nobel Prize
Joshua Lederburg Collection
with Joshua Lederberg - (requires ISDN+ modem and RealPlayer)
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:
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:
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
1975 Nobel Prize
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,
of Age of Animal Virology, ASM News 65, 1999. p.334
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 doesnt 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.
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.
and Maurice Wilkins, together with James Watson, describe the double-helix
structure of DNA. The chemical structure is based on x-ray crystallography of
DNA done by Rosalind Franklin. Crick, Wilkins and Watson are awarded the Nobel
Prize in Medicine and Physiology in 1962
1962 Nobel Prize
DNA Helix Turns 40, ASM News 60,1994. p.28 [PDF]
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.
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.
Publication of The Microbes
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 machineryA 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 [PDF]
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 and Physiology
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
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
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
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:
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
Ochiai, K., T. Yamanaka, K. Kimura, and O. Sawada. 1959. Nippon lji. 1861:
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
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 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:
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
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:
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 and Physiology in 1965
1965 Nobel Prize
Jacob, F., D. Perrin, C. Sanchez, and J. Monod. 1960. Loperon: Groupe de
genes a lexpression coordonne par un operateur. Compt. Rendu. Acad. Sci. 245:
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,
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 and Physiology in 1968
1968 Nobel Prize
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 and 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:
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 and 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
Holliday, R. 1964. A mechanism for gene conversion in fungi. Gen. Res. 5:
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. Natl. Acad. Sci.
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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
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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
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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
Bruce Ames uses autotrophic strains of Salmonella
typhimurium to screen for mutagens and potential carcinogens. The test is based on a
determination of whether exposure to a particular chemical alters the mutation rate of the
microorganism. There is a high correlation between mutagenicity and carcinogenicity in the
Smith, D. E., and B. N. Ames. 1966. Phosphoribosyladenosine monophosphate, an
intermediate in histadine biosynthesis. J. Biol. Chem. 240: 3056-3063.
Jon Beckwith and Ethan Signer transpose the lac region of E.
coli into another microorganism to demonstrate genetic control. The implication of
this work is the realization that chromosomes could be redesigned and genes moved.
Beckwith, H. R.[sic] and E. T. Signer. 1966. Transposition of the lac
region of E. coli. I. Inversion of the lac operon and transduction of the lacoperan
by (phi)80. J. Mol. Biol. 19: 254. In Microbiology: A Centenary Perspective, edited
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William Kirby and Alfred Bauer establish
standards for antibiotic susceptibility testing based on a single disc diffusion procedure
that distinguishes susceptible strains of bacteria from their resistant variants. This
method permits clinical laboratories to provide physicians with accurate, reproducible,
and reliable information with which to chose antimicrobials.
Bauer, A. W., W. M. M. Kirby, J. C. Sherris, and M. Turck. 1966. Antibiotic
susceptibility testing by a standardized single disk method. Am. J. Clin. Path. 45:
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Walter Gilbert and Mark Ptashne isolate the
repressor regulatory molecules postulated by Jacob and Monod. Gilbert isolates the lac
repressor protein and Ptashne purifies the lamda repressor from bacteriophage. The
repressor protein recognizes a specific site on the genome and binds to the site
preventing transmission of DNA into RNA. Repressors are a key element of regulatory
pathways and affect reaction by genes to environmental signals.
Gilbert, W. and B. Muller-Hill. 1966. Isolation of the lac repressor. Proc.
natl. Acad. Sci. USA 56: 1891-1898.
Ptashne, M. 1967. Isolation of the phage repressor. Proc. Natl. Acad. Sci. USA 57:
J. Woodland Hastings shows that Vibrio fischeri, a luminous species of
bacterium, produces a diffusible compound, termed an autioinducer, which accumulates in
the medium during growth. This phenomenon allows the bacterium to sense its elevated
density. The concept is analogous to the production of pheromones in higher organisms.
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Hastings, J. W., and Q. H. Gibson. 1967. The role of oxygen in the photoexcited
luminescence of bacterial luciferose [Photobacterium fischeri] J. Biol. Chem. 242:
Waclaw Szybalski and William Summers use the bacteriophage T7 to show
that only one DNA strand acts as a template for RNA synthesis. They use the technique of
DNA-RNA hybridization to anneal the newly synthesized RNA to a parent DNA strand.
Summers, W. C. and W. Szybalski. 1967. Y-Irradiation of deoxyribonucleic acid in
dilute solutions: I. A sensitive method for detection of single-strand breaks of
polydisperse DNA samples (bacteriophage, Sarcina lutea, Escherichia coli,
Bacillus subtilis, Crytophaga johnsoni). J. Mol. Biol. 26:
Summers, W. C. and W. Szybalski. 1967. Gamma-irradiation of deoxyribonucleic
acid in dilute solutions: II. Molecular mechanisms responsible for inactivation of phage,
its transfecting DNA, and bacterial transforming activity. J. Mol. Biol. 26:
Theodor O. Diener discovers viroids, plant viruses that do not have a protein
capsid. The infectious agent is a low molecular weight RNA that contains no protein
capsid. Among the plants that are affected are potatoes, coconuts, and tomatos.
Diener, T. O. 1967. Potato spindle-tuber virus; a plant virus with properties of
free nucleic acid. Science 158: 378-381.
Thomas Brock identifies the thermophile bacterium Thermus aquaticus from
which heat stable DNA polymerase is later isolated and used in the polymerase chain
reaction. Brock became interested in microbial mats during a trip to Yellowstone. It was
believed at the time that the upper limit for bacterial growth was 73 degrees centigrade.
Brock isolated a pink material that was growing at 85 degrees centigrade. Later the
bacterium was cultured and ultraviolet irradiation was used to prove growth was taking
place. Isolation and culture of this organism later leads to the discovery of the domain
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Brock, T. D. 1967. Micro-organisms adapted to high temperatures. Nature 214;
Brock, T.D. 1967. Life at high temperatures. Science 158:1012-19. In
Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999,
R. John Collier describes the mechanism by which diphtheria toxin
inhibits protein synthesis in a cell-free system from recticulocytes. This is the first
definition at the molecular level of the function of a bacterial protein virulence factor.
Collier, R. J. 1967. Effect of diphtheria toxin on protein synthesis:
Inactivation of one of the transfer factors. J. Mol. Biol. 25: 83-89. In
Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999,
Werner Arber shows that bacterial cells contain highly specific enzymes
that add methyl groups to adenosine and cytosine at recognition sites. Methylation is a
defensive mechanism of the cell preventing hydrolysis of the parent DNA by nucleases in
the cell. These nucleases protect against the introduction of foreign DNA. With Nathans
and Smith, Arber is awarded the Nobel Prize in Medicine and Physiology in 1978
1978 Nobel Prize
Arber, W. and U. Kehnlein. 1967. Mutational loss of B-specific restriction of
the bacteriophage fd. Path. Micro. 30: 946-952.
Marvin Bryant, the Wolins, and Ralph Wolfe show that anaerobic bacteria can
effect interspecies transfer of H2. One strain oxidizes ethanol to acetate and the other
reduces carbon dioxide to methane. This provides an explanation for the interactions of
anaerobes during the fermentation of complex organic compounds.
M.P. Bryant, E.A. Wolin, M.J. Wolin, and R.S. Wolfe. 1967. Methanobacillus
omelianskii, a symbiotic association of two species of bacteria. Archiv. Fur
Mikrobiologie 59:20-31. In Microbiology: A Centenary Perspective, edited by Wolfgang K.
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Lynn Margulis proposes that endosymbiosis has led
to the generation of mitochondria and chloroplasts from bacterial progenitors.
Margulis, L. 1968. Evolutionary criteria in Thallophytes: A radical alternative.
Science 161: 1020-1022.
Charles Helmstetter and Stephen Cooper, using the "baby
machine" establish the rules for replication in the Escherichia coli cell
Cooper, S. and C. Helmstetter. 1968. Chromosome replication and the division
cycle of Escherichia coli B/r. J. Mol. Biol. 31: 519-540
From the Woods Hole Marine Station summer research program came the discovery by Levin
and Bang that the lysate of the amebocytes from the hemolymph of the horseshoe
crab, Limulus polyphermus clots in the presence of the lipopolysaccharides in the
cell walls of gram-negative bacteria. This finding lead to the development of an in vitro
assay for the pyrogens that contaminated injectable products that replaced the rabbit
Levin, J., and F. B. Bang. "Clottable Proetin in Limulus: Its Localization
and Kinetics of its Coagulation by Endotoxin." Thrombosis et Diathesis Haemorrhagica
Bacterial Endotoxin Test:
Julius Adler describes chemoreceptors in bacteria, a
discovery demonstrating that bacteria can sense and process environmental information. His
method involved inserting a tube of chemicals into a solution of bacteria and then
counting the number of bacteria that swam to the chemical.
Adler, J. 1969. Chemoreceptors in bacteria. Science 166: 1588-1597.
In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press.
1999, p.428 [PDF]
Don Brenner and colleagues establish a more reliable basis for the
classification of clinical isolates among members of the Enterobacteriaceae. They use
nucleic acid reassociation in which denatured DNA labelled DNA fragments of one organism
are reacted under annealing conditions with DNA of another organism. Studies on many
species have proven the value of DNA-DNA hybridization to define a species.
Brenner, D.J., G.R. Fanning, K.E. Johnson, R.V. Citrella, and S. Falkow.1969.
Polynucleotide sequence relationships among members of the Enteriobactiaceae. J.
Bacteriol. 98:637-50. In Microbiology: A Centenary Perspective, edited by Wolfgang K.
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Hamilton Smith and Kent W. Wilcox describe
the action of restriction enzymes, which are a bacterial defense mechanism, but which
quickly become tools for sizing DNA. They report the isolation of an enzyme capable of
cleaving a double strand T7 DNA but not native DNA from the source organism, Haemophilus
influenzae, or denatured DNA. They conclude that the enzyme has the ability to
recognize specific DNA sequences. With Nathans and Arber,
Smith is awarded the Nobel Prize in Medicine and Physiology in 1978
1978 Nobel Prize
Smith, H. O. and K. W. Wilcox. 1970. A restriction enzyme from Haemophilus
influenzae: I. Purification and general properties. J. Mol. Biol. 51: 379-391.
In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999,
Howard Temin and David Baltimore independently discover
reverse transcriptase in RNA viruses. The enzyme, reverse transcriptase, uses single
stranded RNA as a template to synthesize a single stranded DNA complement . The latter
then acts as a template for a complementary DNA chain consistent with general replication
mechanisms. This process establishes a pathway for genetic information flow from RNA to
DNA. Temin postulated that certain viruses possess an enzyme in their viral coat that
facilitates the duplication of viral genes into the DNA of a cell. He called this gene a
proviral gene and speculated that the genetic information was conveyed from RNA to DNA by
the enzyme of the gene. With Dulbecco, Baltimore and Temin are awarded the Nobel Prize in
Medicine and Physiology in 1975
1975 Nobel Prize
Baltimore, D. 1970. Viral RNA-dependent DNA polymerase. Nature 226:
1209-1211. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM
Press. 1999, p.518 [PDF]
Temin, H. M. and S. Mizutani. 1970. RNA-dependent DNA polymerase in virions of
Rous carcinoma virus. Nature 226: 1211-1213. In Microbiology: A Centenary
Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.522 [PDF]
Joan Mertz and Ronald W. Davis establish that the R1
restriction endonuclease from Escherichia coli cuts DNA at a specific site four to
six nucleotides long. The DNA sequence that is cut is complementary to other DNA cut by
the same enzyme. This opens the way for cloning.
Mertz, J. E. and R. W. Davis. 1972. Cleavage of DNA by R1 restriction
endonuclease generates cohesive ends. Proc. Natl. Acad. Sci USA 69: 3370-3374.
Paul Berg constructs a recombinant DNA molecule from viral and bacterial DNA. . With Gilbert and Sanger, Berg is awarded the Noble Prize in
Chemistry in 1980
1980 Nobel Prize
Jackson, D. A., R. H. Symons, and P. Berg. 1972. Biochemical method for
inserting new genetic infromationinto DNA of simian virus 40: Circular SV 40 DNA molecules
containing lamda phage genes and the galactose operon of Escherichia coli. Proc. Natl.
Acad. Sci. 69: 2904-2909. In Microbiology: A Centenary Perspective, edited by
Wolfgang K. Joklik, ASM Press. 1999, p.528 [PDF]
Cohen, Annie Chang, Robert Helling, and Herbert Boyer show that if DNA is
broken into fragments and combined with plasmid DNA, such recombinant DNA molecules will
reproduce if inserted into bacterial cells. They show that plasmids act as vectors for
maintaining cloned genes. Boyer was researching restriction enzymes to determine whether
they could cut the DNA at certain points. Cohen was isolating plasmids from E. coli.
Cohen and Boyer met at a conference in Hawaii and shared their information.The discovery
is a major breakthrough for genetic engineering, allowing for such advances as gene
cloning and the modification of genes. The discovery also raised fears about accidental
production of organisms with unexpected disease potential.
Cohen, S. N., A. C. Y. Chang, H. W. Boyer, and R. B. Helling. 1973. Construction
of biologically functional bacterial plasmids in vitro. Proc. Natl. Acad. Sci. USA 70:
3240-3244. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik,
ASM Press. 1999, p.178 [PDF]
Daniel Nathans, George Khoury, Malcolm Martin use restriction enzymes to
cleave SV40 DNA into specific segments and then construct a complete physical map of the
Adler, S. P., and D. Nathans. 1973. Studies of SV40 DNA: V. Conversion of
circular to linear SV40 DNA by restriction endonuclease from Escherichia coli B.
Biochim. Biophys. Acta. 299: 177-188.
Khoury, G., M.A. Martin, T.N. Lee, K.J. Dana, and D. Nathans. 1973. A map of
simian virus 40 transcription sites expressed in productively infected cells. J. Mol.
Biol. 78:377-89. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik,
ASM Press. 1999, p.536 [PDF]
George Laver and Robert Webster demonstrate that the genomes of
influenza virus strains responsible for pandemics possess genome fragments acquired by
genome segment reassortment from influenza strains circulating in animals.
Laver, G. and R.G. Webster. 1973. Studies on the origin of pandemic influenza.
III. Evidence implicating duck and equine influenza as possible progenitors of the Hong
Kong strain of human influenza, Virology. 51:391-93
Peter Doherty and Rolf Zinkernagl show that the cellular immune system
requires that lymphocytes recognize both the virus invader and major histocompatibility
antigens in order to kill virus-infected cells. This establishes the principle of
simultaneous recognition, of both self and non-self molecules, as the basis of the
specificity of the cellular immune system. Doherty and Zinkernagl are awarded the Nobel
Prize in Medicine and Physiology in 1996
1996 Nobel Prize
Zinkernagel, R. M. and P. C. Doherty. 1973. Cytotoxic thymus-derived lymphocytes
in cerebrospinal fluid of mice with lymphocytic choriomeningitis. J. Exp. Med. 138:
Studies Illuminate the Nature of Immunity, ASM News 65, 1999, p.340
Paul Berg, David Baltimore, Herbert Boyer, Stanley Cohen,
Ronald Davis, David Hogness, Richard Roblin, James Watson, Sherman Weissman, and Norton
Zinder publish a letter in "Nature, Science, and the Proceedings of the National
Academy of Sciences". They recommend that scientists defer from creating
microorganisms with novel genes for drug resistance and toxin production, and also defer
inserting cancer causing genes from viruses into bacterial host cells. They also suggest
that the Federal government set guidelines for the conduct of research and that scientists
themselves organize a conference to discuss these issues.
This appeared in the letters to Science from Paul Berg et al as: Potential
biohazards of recombinant DNA. Science 185: 303.
Ralph Wolfe and Charles Taylor describe a novel coenzyme from a methanogen. This
is the first of five new coenzymes, two of which are also widely distributed among the
C.D. Taylor and R.S. Wolfe. 1974. Structure and methylation of coenzyme M
(HSCH2CH2SO3). J. Biol. Chem. 249:4879-85. In Microbiology: A Centenary Perspective,
edited by Wolfgang K. Joklik, ASM Press. 1999, p.256 [PDF]
David Hogness and Michael Grunstein develop colony hybridization,
a technique to transfer bacterial colonies to filters, lyse, and fix the DNA. Labeled
probes of single stranded DNA, complementary to the fixed DNA, can be applied to determine
the identity of the unknown bacterium.
Kreigstein, H. J. and D. S. Hogness. 1974. Mechanism of DNA replication in Drosophila
chromosomes: Structure and replication forks and evidence for bidirectionality. Proc.
Natl. Acad. Sci. USA 71: 131-139.
Jeff Schell and Marc Van Montagu discover that a circular strand of DNA (a
plasmid) carried by A. tumefaciens transforms plant cells into tumor cells.
Van Larabeke, N., Engler, G., Holsters, M., Elcacker, SVD, Zaenen, I., Schilperoort,
R.A., and Schell, J. 1974. Large plasmid in Agrobacterium tumefaciens essential for
crown gall-inducing ability. Nature 252:169
The Asilomar Conference is convened to discuss possible
problems associated with gene cloning. A one-year moratorium, as well as guidelines for
cloning research and for genetic engineering, is suggested.
This is described in 1975 as: Genetics: Conference sets strict controls to
replace moratorium. Science 187: 931-934.
Kyung (June) Kwon-Chung describes sexual reproduction in the fungus, Cryptococcus
Kwon-Chung, K. J. 1975. Filobasidiella, the perfect state of Cryptococcus
neoformans. Mycologia 57: 1197-12
C.M. Wei and Bernard Moss, and Aaron Shatkin and colleagues
show that messenger RNA contains a specific nucleotide cap at its 5-prime end that affects
correct processing during translation.
C.M. Wei and B. Moss. 1975. Methylated nucleotides block the 5-terminus of
vaccinia virus mRNA. Proc. Natl. Acad. Sci. 72:318-22. In Microbiology: A Centenary
Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.550 [PDF]
Y. Furuichi, M. Morgan, S. Muthukrishnan, and A. Shatkin. 1975. Reovirus
messsenger RNA contains a methylated blocked 5-terminal strucure:
m7G(5)ppp(5)GmpCp. Proc. Natl. Acad. Sci. 72:362-67. In Microbiology: A
Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999, p.556 [PDF]
Kohler and Cesar Milstein physically fuse mouse lymphocytes with neoplastic mouse
plasma cells to yield hybridomas that can produce specific antibodies and can survive
indefinitely in tissue culture. This approach offers a limitless supply of monoclonal
antibodies. Monoclonal antibodies permit the generation of diagnostic tests that are
highly specific and also function as probes to study cell function. With Jerne, Kohler and
Milstein are awarded the Nobel Prize in Medicine and Physiology in 1984
1984 Nobel Prize
Kohler, G. and C. Milstein. 1975. Continuous cultures of fused cells secreting
antibody of predefined specificity. Nature 256: 495-497.
Thomas Cech and Sidney Altman independently show
that RNA can serve directly as a catalyst of hydrolytic reaction. Altman investigated
RNase P from Escherichia coli and Cech studied the rRNA gene from Tetrahymena
thermophilia. They each determined that an RNA component could be separated from
protein while retaining catalytic activity. Cech and Altman are awarded the Nobel Prize in
Chemistry in 1989
1989 Nobel Prize
Altman, S. 1975. Biosynthesis of transfer RNA in Escherichia coli. Cell 4:
Cech, T. and M. L. Pardue. 1976. Electron microscopy of DNA crosslinked with
trimethylpsorlen: Test of the secondary nature of eukaryotic inverted repeat sequences.
Proc. Natl. Acad. Sci. USA 73: 2644-2648.
J. Michael Bishop and Harold Varmus identify oncogenes from the
Rous sarcoma virus that can also be found in the cells of normal animals, including
humans. Proto-oncogenes appear to be essential for normal development but can become
cancer genes when cellular regulators are damaged or modified. Bishop and Varmus are
awarded the Nobel Prize in Medicine and Physiology in 1989
1989 Nobel Prize
Stehelin, D., R. V. Guntaka, H. E. Varmus, and J. Michael Bishop. 1976.
Purification of DNA complementary to nucleotide sequences required for neoplastic
transformation of fibroblasts by avian sarcoma viruses. J. Mol. Biol. 101: 349-365.
Stehelin,D. H.E. Varmus, J.M. Bishop, and P. Vogt. 1976. DNA related to the
transforming gene(s) of avian sarcoma virus is present in normal avian DNA. Nature
260:170-73. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM
Press. 1999, p.562 [PDF]
The National Institutes of Health issues guidelines for the conduct of NIH
supported research using recombinant DNA technology. The guidelines define physical and
biological containment levels for research.
Recombinant DNA Research Guidelines, 41 Fed. Reg. 27902, 1976.
William Trager and Jim Jensen succeed in
cultivating the human malaria parasite Plasmodium falciparum, which allowed its
study, in the laboratory, for the first time.
Trager, W., Jensen, J. B. 1976. Human malaria parasites in continuous
culture. Science 193: 673-5
uses ribosomal RNA analysis to identify a third form of life, the Archea, whose
genetic makeup is distinct from but related to both Bacteria and Eucaryea.
Woese, C. R. and G. E. Fox. 1977. Phylogenetic structure of the prokaryotic
domain: The primary kingdoms. Proc. Natl. Acad. Sci. USA 74: 5088-5090. In
Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press. 1999,
G.E. Fox, K.R. Pechman, and C.R. Woese. 1977. Comparative cataloging of
16S ribosomal ribonucleic acid: molecular approach to procaryotic systematics. Int. J.
Syst. Bacteriol. 27:44-57. In Microbiology: A Centenary Perspective, edited by Wolfgang K.
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Louise Chow and Richard Roberts, and independently Phillip
Sharp show that genes are not uninterrupted strands of genes but are interspersed with
non-coding segments that do not specify protein structure. Both make the discovery with
adenovirus while looking at viral protein synthesis. This finding establishes a
fundamental distinction in information processing between procaryotic and eucaryotic
organisms. Roberts and Sharp are awarded the Nobel Prize in Medicine and Physiology in
1993 Nobel Prize
Chow, L. T., R. E. Gelinas, T. R. Broker and R. J. Roberts. 1977. An amazing
sequence arrangement at the 5 ends of adenovirus 2 messenger RNA. Cell 12:
1-8. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM Press.
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S.M. Berget, C. Moore, and P.A. Sharpe. 1977. Spliced segements at the
5-terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. 74:3171-75. In
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Walter Gilbert and Fred Sanger independently develop methods to
determine the exact sequence of DNA. Gilbert uses the technique to determine the sequence
of the operon of a bacterial genome. Sanger and colleagues use the technique to determine
the sequence of all 5375 nucleotides of the bacteriophage phi-X174, the first complete
determination of the genome of an organism. With Berg, Gilbert and Sanger are awarded the
Nobel Prize in Chemistry in 1980
1980 Nobel Prize
Maxam, A. M. and W. Gilbert. 1977. A new method for sequencing DNA. Proc. Natl.
Acad. Sci. USA 74: 560.
Sanger, F., G.M. Air, B.G. Barrell, N.L. Brown, A.R. Coulson, J.C. Fiddes, C.A..
Hutchison, P.M. Slocombe, and M. Smith. 1977. Nucleotide sequence of bacteriophage phi
X174 DNA. Nature. 165:687-95
Centers for Disease Control researchers Joseph McDade and Charles C. Shepard
isolate and identify Legionella pneumophilia as the bacterial pathogen in a newly
discovered pulmonary disease. There are now known to be more that 40 species which occur
in water settings.
McDade, J. E., C. C. Sheperd, D. W. Fraser, T. R. Tsai, M. A. Redus, W. R.
Dowdle, and Laboratory Investigation Team. 1977. Legionaires disease: Isolation of a
bacterium and demonstration of its role in other respiratory disease. N. Engl. J. Med. 297:
1197-1203. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM
Press. 1999, p.62 [PDF]
Mothers in Old Lyme (CT) describe a high level of illness among children, which is
diagnosed as juvenile rheumatoid arthritis. A research group led by Alan Steere
finally begins to investigate in 1977 and using an epidemiological approach finds that
deer ticks are the vector.
Steere, A. C., S. E. Malawista, D. R. Snydman, R. E. Shope, W. A. Andiman, M. R.
Ross, and F. M. Steele. 1977. Lyme arthritis: An epidemic of oligoarticular arthritis in
children and adults in three Connecticut communities. Arthritis Rheum. 20: 7-17.
Eugene Nester, Milton Gordon and Mary-Dell Chilton show that genes on the A.
tumefaciens plasmid are transferred into infected plant cells.
Chilton, M.-D., M.H. Drummond, D.J. Merlo, Daniela Sciaky, A.L. Montoya, M.P. Gordon
and E.W. Nester Stable incorporation of plasmid DNA into higher plant cells: the molecular
basis of crown gall tumorigenesis. Cell 11:263-271
Microbiology: Century of Discovery, with Golden Years Ahead,
ASM News 65, 1999, p.358
Holger Jannasch shows that microbial sulfur oxidation is a source of
energy for dense animal colonies in the absence of light at deep sea hydrothermal vents.
Jannasch and Wirsen use a device for sampling of microbial populations at depths of 6000
meters and then study the population without decompression.
H.W. Jannasch and C.O. Wirsen. 1977. Retrieval of concentrated and
undecompressed microbial populations from the deep sea. Appl. Environ. Microbiol.
33:642-46. In Microbiology: A Centenary Perspective, edited by Wolfgang K. Joklik, ASM
Press. 1999, p.280 [PDF]
Wirsen, C. O. and H. W. Jannasch. 1978. Physiological and morphological
observations on Thiovulum sp. J. Bacteriol. 136: 765-774.
Smallpox (variola) is declared officially
eliminated; last natural case seen in Somalia in 1977. Small quantities remain held under
tightly controlled conditions in the U.S. and former U.S.S.R. THE ONLY MICROBIAL
DISEASE EVER COMPLETELY DEFEATED.
Victory Over Variola, ASM News 44, 1978. p. 639 [PDF]
Arita, I. 1979. Virological evidence for the success of the smallpox eradication
programme. Nature 279: 293-298.
Henderson, D.A. 1979. The saga of smallpox eradication: an end and a beginning.
Can. J. Pub. Hlth. 70:212-27
The U. S. Supreme Court rules that microorganisms altered
in the laboratory can be patented.
Ananda Chakrabarty receives a patent for metabolizing Pseudomonads
developed by conjugation that can degrade camphor, octene, salicylate, and
United States Patent #425944. Issued March 31, 1981.
Helen Whiteley and Ernest Schnepf at the University of Washington clone a Bt
Schnepf, H.E., and H. R. Whiteley. Cloning and expression of the Bacillus
thuringiensis crystal protein in Escherichia coli. Proc. Nat. Acad. Sci.78:2893-2897
U. S. Pharmaceutical manufacturer Eli Lilly markets the
first genetically-engineered human insulin.
Stanley Prusiner finds evidence that a class of
infectious proteins he call prions cause scrapie, a fatal neurodegenerative disease of
sheep. Prusiner is awarded the Nobel Prize in Medicine and Physiology in 1997
1997 Nobel Prize
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