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Max Delbrück

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Ernst Peter Fischer, Max Delbrück, Genetics , Volume 177, Issue 2, 1 October 2007, Pages 673–676, https://doi.org/10.1093/genetics/177.2.673

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Anecdotal, Historical and Critical Commentaries on Genetics

Edited by James F. Crow and William F. Dove

MAX DELBRÜCK (1906–1981) played a crucial role in getting molecular biology as we know it on its successful way. Thus, in the 1940s, after emigrating to the United States, he started a new science. However, he had begun in the oldest science as a student of astronomy in the 1920s while still in his native country, Germany. He soon left this field since it was during those student years that the lasting revolutionary science of quantum mechanics made its debut. Thus, Max eagerly switched to theoretical physics in which he obtained his Ph.D. in 1929. From then on he tried to find out if the new understanding of the stability of atoms and the properties of matter could help in explaining the nature of genes. This quest led to developing what the famous Austrian Nobel laureate Erwin Schrödinger called “Delbrück's model.” In his influential book, What is Life? (1944), Schrödinger contributed to Max's fame by expressing the following opinion: “If the Delbrück picture should fail, we would have to give up further attempts” ( Schrödinger 1944 , p. 61), meaning further attempts in using physics to understand what genes are and how they act.

In 1969, Max shared the Nobel Prize for Physiology and Medicine with Salvadore Luria and Alfred Hershey. Since they were the first to publish on bacterial genetics, their work opened the field. Yet even as the object of highest recognition possible in the scientific world, Max remained totally unpretentious. He always directed friends and coworkers to call him Max; anyone referring to him as Dr. Delbrück or Professor Delbrück would have been rebuked. This essay, then, will refer to him as he wished to be addressed.

Max was born in Berlin in 1906 as the seventh child of the famous historian Hans Delbrück and his wife Lina. There, he was raised in the upscale suburb of Berlin called Grünewald, where today one can find a street named after Max's father. The neighbors of the Delbrücks consisted mainly of distinguished academic families with famous names like Bonhoeffer (a professor of psychiatry) and Harnack (a professor of theology). It was a marvelous life until in 1914, when “the dam broke and swept away four decades of peace,” as Max put it, adding that “my memories start with the war years: hunger, cold, substitute teachers, social pressure to engage in dismal patriotic war games.”

To see and handle these old books, 300 years old, was a tremendous experience, especially when I found in one of them speculations about the celestial harmonies expressed in terms of musical notes. ( Fischer and Lipson 1988 , p. 23)

Despite experiences like this, Max's choice of astronomy turned out to be a bad one since the exciting science being developed in the mid 1920s was quantum mechanics. In the spring of 1925, 23-year-old Werner Heisenberg had conceived of a totally new way of describing atoms and their particles. In the next year Erwin Schrödinger followed suit with his version of the new physics called wave mechanics. In early 1926, Heisenberg came to Berlin to give a seminar that Max attended. Although he did not understand a word of it, Max realized by picking up remarks from Albert Einstein, who was sitting in the first row, that he had witnessed a very important scientific development. Therefore, Max switched fields to study the new quantum theory. He went to Göttingen as a graduate student of Max Born, eventually completing a “rather dull” Ph.D. thesis on the lithium molecule. While working on this he started to wonder about the relevance of the new revolutionary insights into the nature of matter and light.

One of the puzzling insights physicists had to face was the fact that two classical concepts were needed to describe or understand light as well as matter—the concept of a wave and the concept of a particle. The great Danish physicist Niels Bohr called pairs of concepts like this complementary. By this, he meant that they together provide a complete description of the phenomena under consideration, while the use of one of them excluded the simultaneous application of the other. Bohr considered it likely that the idea of complementarity would eventually pervade all of science. He believed that a deep understanding of nature would come about by using complementary concepts and/or arguments. He repeated and restated this suggestion in the early 1930s in many lectures, including the 1932 opening lecture of an International Congress of Light Therapists that Max attended.

At that time, with the help of a fellowship from the Rockefeller Foundation, Max was doing some postdoctoral studies in Bohr's institute in Copenhagen. He was not really happy to be in physics since the days of great discoveries seemed to have ended in 1928 when Paul Dirac managed to fuse quantum mechanics and relativity theory. Of course, there were many details left to be worked out, but Max had not switched from the stars to the quantum to do that. He was looking for a field that needed new ideas and he saw his chance when he attended Bohr's 1932 lecture entitled “Light and Life.”

In physics it is obvious that even in the simplest case such as an electron running around a proton one can do classical physics until one's dying day and never get a hydrogen atom out of it. In order to achieve this, one has to use the complementary approach. If one looks at even the simplest kind of cell, one knows it consists of the usual elements of organic chemistry and otherwise obeys the laws of physics. One can analyze any number of compounds in it but one will never get a living bacterium out of it, unless one introduces totally new and complementary points of view. ( Fischer and Lipson 1988 , p. 82)

The idea of complementarity has been described in such detail because of its importance to Max's thinking: “It has through the years provided the sole motivation for my work,” as Max wrote in 1962 when he invited Bohr to deliver another lecture about light and life 30 years after the influential first one ( Bohr 1963 ).

When one tries to reconstruct the ideas that emerged in Max's thinking while listening to Bohr we are led to a view of his future research, summarized below.

The new physics had started by analyzing the interaction of light and matter and realizing that it occurs in quantum jumps. These quanta helped to explain the stability of atoms (and thereby of matter), which was discovered with the help of a simple system, namely the hydrogen atom consisting only of two elements—an electron and a proton. To get a new study of biology one had to start by analyzing the interaction of light and life. Further, one needed to find a simple system that allowed investigation of the basic property of living systems: their reproduction and the generation of stable variants (mutations). Thus, Max started to look for the “hydrogen atom” in biology, i.e ., a living entity that did little more than replicate. But first, he had to learn to do biology!

After working with Bohr, Max returned to Berlin to become assistant to Lise Meitner. There, his main goal of learning biology was pursued in private. He contacted the Russian geneticist Nicolai Timoféeff-Ressovsky, who was working with Drosophila, studying the genetic changes induced by different wavelengths of radiation. The two men collaborated with the physicist K. G. Zimmer to eventually produce an article, “About the nature of the gene mutation and the gene structure” that was published in 1935 and contained what was already referred to above as Delbrück's model of the gene ( Timoféeff - Ressovsky et al . 1935 ). After presenting quantitative results of the effects of ionizing radiation on mutation frequency, in a separate chapter Max worked out a quantum mechanical model of the gene, calling it an “Atomverband”—a collection of atoms—thereby connecting genetics with physics and chemistry and opening the abstract gene for a concrete analysis using the exact sciences.

In 1937 Max was offered another fellowship by the Rockefeller Foundation to continue his biological work in the United States. He chose the California Institute of Technology where Thomas H. Morgan had set up his Drosophila laboratory. After Max quickly discovered that the fruit fly could not fulfill his dream of connecting physics to biology, he feared that he would be a failure. At that point, Max was saved by meeting Emory Ellis, who was analyzing bacterial viruses. Max immediately identified them as “something like atoms in biology” ( Fischer and Lipson 1988 , p. 113).

At this point, the reader should recall that in 1937 it was impossible to distinguish the terms “phage,” “protein,” or “gene.” Genes were assumed to be proteins, some of which were known to be autocatalytic enzymes. This was one way to interpret the multiplication of phage. To Max, it was of no importance to distinguish between phage, protein, and gene as long as he could study the key properties of a reproducing biological system that allowed easy quantification. He was not interested in genes but in replication as the basic property of life (compared to physical stability as the basic properties of atoms).

Max collaborated with Ellis to investigate “The growth of bacteriophage” ( Ellis and Delbrück 1939 ). This article describes the beginning of modern phage work: presenting one-step-growth curves and a way to determine the concentration of bacterial viruses in solution. It makes use of statistical arguments from physics, thereby creating a first quantitative basis of genetic analysis.

Since Ellis was paid to follow up other lines of research Max continued with phage all by himself when he transferred to Vanderbilt University in Nashville after the beginning of World War II. Then, in December 1940 he met Salvadore Luria at a meeting of the American Association for the Advancement of Science in Philadelphia. Although the two differed in their goals, they agreed to join forces. Max wanted to study and understand replication while Luria was interested in the gene. Since, in the early 1940s, the known laws of inheritance were valid only for organisms that reproduced sexually, no one knew for sure if these creatures even had genes.

Nevertheless, both scientists wanted to see what a virus was doing in the black box of a bacterium. When they discovered that two phages acting upon the same host strongly interfered with each other's multiplication, Max was very excited. He saw a chance to apply physical terms like interference and the idea of mutual exclusion that characterizes a complementary situation to a biological process. In 1947 he wrote about “the principle of mutual exclusion” ( Delbrück 1947 ) and he experienced a letdown when it turned out that the real explanation resulted from recombination. While every other biological scientist was happy to see that phages fit into the general genetic framework Max was disappointed that his dream of finding a definite complementarity in biology did not come true. Finally, in 1953 the double-helical structure of DNA was discovered and Max gave up research in genetics altogether. The model proposed by James Watson and Francis Crick ( Watson and Crick 1953 ) achieved for biology what physics had missed in the early decades of the 20th century: a molecular model that would explain basic phenomena in classical terms without reference to complementarity. Max felt that genetics had been reduced to chemistry, a field in which he was not really interested.

By fast-forwarding to the early 1950s we have slipped over Max's most important contribution to the rising science of genetics ( Luria and Delbrück 1943 ). During his collaboration with Luria, in the war years, the German–Italian pair had observed a phenomenon they called secondary growth. It had to be due to resistant strains that appeared a few hours after a susceptible culture of Escherichia coli had been lysed. In April 1941 Max sent a note to Luria, telling him that he felt “that the rise of the secondary culture would be an interesting and attackable problem for future collaboration.” As they started working on it, Luria discovered first to his annoyance that the number of resistant E. coli cells was subject to great day-to-day fluctuations. After observing a slot machine it occurred to Luria that he was analyzing the wrong numbers. Instead of thinking about the number of resistants, he felt he should look at the fluctuations ( Luria 1984 ). Max, the physicist, immediately recognized which statistical distribution could be applied to the phenomenon, and he worked out a theoretical explanation. Together, they created the famous fluctuation test that led to two important insights. First, it made clear that phage-resistant mutants originated by spontaneous mutation (as Darwinian evolution would expect) and, second, that a mathematical analysis of the fluctuations allowed the precise determination of mutation rates. The joint article by Max and Luria provided statistical evidence for the existence of genes in bacteria and allowed the calculation of their rates of spontaneous mutation. Thus, the field of bacterial genetics was begun, and this science exploded when in 1946 Edward Tatum and Joshua Lederberg discovered that bacteria had a sex life after all ( Lederberg and Tatum 1946 ).

Max considered Phycomyces “as something analogous to a gadget in physics” which he wanted “to analyze in great detail” thereby hoping “when this analysis is carried sufficiently far, it will run into a paradoxical situation analogous to that into which classical physics ran in its attempts to analyze atomic phenomena. This, of course, has been my ulterior motive in biology from the beginning. What I have in mind is an application of the complementarity principle not in a form which is just vaguely analogous to the dividing line between observer and object, but something much more closely related to the physics situation, springing directly from the individuality and indivisibility of the quantum processes.”

Unfortunately, once again Max's dream did not come true (see Cerdà - Olmedo and Lipson 1987 ). We leave the research on Phycomyces in the hands of the scientists still working at it and conclude by mentioning some of Max's influence on modern science. With this I do not mean the functioning of Cold Spring Harbor Laboratory or the Genetics Institute in Cologne or the University of Constance, which he helped to get underway in the late 1960s. Rather, I suggest that genetics is still a science that can be treated as physics. Max was proud to tell everybody that modern biology was the result of what physicists did.

One might question if this is good for science in the sense that the people who work in this field try to understand life solely by looking “for other physical laws,” as Schrödinger put it ( Schrödinger 1944 , p. 73). With these other laws still being laws of physics scientists may miss out on explanations of another kind, e.g ., explanations that are genetical in the sense that they describe the creation of form. One cannot expect to be able to explain the shape of an earlobe or a nose by physical causality alone, since one cannot explain a work of art such as a painting by the force an artist applied or the chemical composition of the colors used. There is more to a shape than physical causality and the science of genetics has to rise to this challenge if it wants to explain the properties of life. Today's molecular biologists should be reminded that already the pioneers of atomic physics (personally known to Max) realized that even atoms cannot be fully understood by physical causality alone. You have to start with the existence of a stationary state— i.e ., a form—to explain the behavior of the basic building blocks of matter. So the question is: How will the appropriate morphogenetic reasoning be incorporated into the modern genetics that at the present is mainly busy sequencing genomes and considering them as physical causes?

To use an expression Max liked: We are still waiting for a “Niels Bohr” in biology as Max used to say, recognizing that in James Watson, we already have had an “Einstein of biology.” As I have discussed, Bohr introduced what became Max's favorite idea into science: the idea of complementarity, which at this point should be stated in a general way.

Complementarity means that for each description of reality there is another one that is equally justified although it contradicts the first one. The classical example is the wave-particle duality of atoms and light. Another complementarity can be found if you look at the ways Newton and Goethe describe color, concentrating on what they meant by “simple.” For Newton light was simple when it consisted of a single wavelength after passing through a prism. For Goethe that light was complicated because it needed an instrument for its production before being seen. Instead, for the German poet the light that came from the sun was simple: It was generated that way and our eyes then made direct use of it from a phenomenological point of view.

Max was convinced that science would achieve a deep understanding of its objects only if it arrived at a complementary description. How can we apply this idea to genes, development, genomes and the like? Max suggested that as along as complementarity is not on the horizon we are not even close to an understanding.

Is there anything else that can we learn from Max's life in science? With respect to the responsibility of researchers, I like Max's idea that a scientist can bring much more change into the world than any politician or military leader and he can do so by just sitting in his office and thinking. And Max loved to do this all his time.

Bohr , N., 1933 Light and Life. Nature 131 : 421 .

Bohr , N., 1963 Licht und Leben—noch einmal. Naturwissenschaften 50 : 725 .

Cerdà - Olmedo , E., and E. D. Lipson (Editors), 1987 Phycomyces . Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

Delbrück , M., 1947 Über Bakteriophagen. Naturwissenschaften 34 : 301 –306.

Ellis , E. L., and M. Delbrück , 1939 The growth of bacteriophage. J. Gen. Physiol. 22 : 365 –384.

Fischer , E. P., 1985 Licht und Leben — Max Delbrück als Wegbereiter der Molekularbiologie . Konstanzer Universitätsverlag, Konstanz, Germany.

Fischer , E. P., and C. Lipson , 1988 Thinking About Science — Max Delbrück and the Origin of Molecular Biology . W. W. Norton, New York.

Lederberg , J., and E. Tatum , 1946 Novel genotypes in mixed cultures of biochemical mutants in bacteria. Cold Spring Harbor Symp. Quant. Biol. XI : 113 –114.

Luria , S. E., 1984 A Slot Machine, A Broken Test Tube . Harper & Row, New York.

Luria , S. E., and M. Delbrück , 1943 Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28 : 491 –511.

Schrödinger , E., 1944 What is Life? Cambridge University Press, Cambridge, UK.

Stent , G. S., and J. D. Watson (Editors), 1966 Phage and the Origin of Molecular Biology . Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

Susman , M., 1995 The Cold Spring Harbor Phage Course (1945–1970): a fiftieth anniversary remembrance. Genetics 139 : 1101 –1106.

Timoféeff - Ressovsky , N., K. G. Zimmer and M. Delbrück , 1935 Über die natur der genmutation und der genstruktur (about the nature of the gene mutation and the gene structure). Nachrichten der Gesellschaft der Wissenschaften zu Göttingen, Math.-Phys. Klasse. Fachgruppe 6 (13): 190 –245.

Watson , J. D., and F. H. C. Crick , 1953 A structure for deoxyribonucleic acid. Nature 171 : 737 –738.

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History of Early Bacteriophage Research and Emergence of Key Concepts in Virology

Published: 22 September 2020
Volume 85 , pages 1093–1112, ( 2020 )

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A. V. Letarov 1 , 2

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The viruses of bacteria – bacteriophages – were discovered 20 years after the discovery of viruses. However, this was mainly the bacteriophage research that, after the first 40 years, yielded the modern concept of the virus and to large extent formed the grounds of the emerging molecular genetics and molecular biology. Many specific aspects of the bacteriophage research history have been addressed in the existing publications. The integral outline of the events that led to the formation of the key concepts of modern virology is presented in this review. This includes the opposition of F. d’Herelle and J. Bordet viewpoints over the nature of the bacteriophage, the history of lysogeny discovery and of determination of the mechanisms of underlying this phenomenon, the work of the Phage group led by M. Delbruck in USA, the development of the genetic analysis of bacteriophages and other research that eventually led to emergence of the concept of the virus (bacteriophage) as a transmissive genetic program. The review also covers a brief history of early applications of the bacteriophages such as phage therapy and phage typing.

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Overview of Bacteriophage Lifecycles and Applications

Bacteriophage Use in Molecular Biology and Biotechnology

Stent, G. S. (1960) Papers on Bacterial Viruses , Boston, Mass., pp. 365, doi: https://doi.org/10.1126/science.134.3471.44-c .

Letarov, A. V. (2019) Modern Concepts of Bacteriophage Biology , DeLi, Moscow.

Schlegel, H. G. (2020) Geschichte der Mikrobiologie , Halle: Deutsche Akademie der Naturforscher Leopoldina, 2004.

Debré, P. (1998) Louis Pasteur , John Hopkins University Press, Baltimore.

Lakhtakia, R. (2014) The legacy of Robert Koch: surmise, search, substantiate, Sultan Qaboos Univ. Med. J. , 14 , e37-e41, doi: https://doi.org/10.12816/0003334 .

Article PubMed PubMed Central Google Scholar

Blevins, S. M., and Bronze, M. S. (2010) Robert Koch and the “golden age” of bacteriology, Int. J. Infect. Dis. , 14 , e744-e751, doi: https://doi.org/10.1016/j.ijid.2009.12.003 .

Article PubMed Google Scholar

Winau, F., and Winau, R. J. M. (2002) Emil von Behring and serum therapy, Microbes Infect. , 4 , 185-188, doi: https://doi.org/10.1016/s1286-4579(01)01526-x .

Kitsenko, O. S., Kitsenko, R. N., and Belova, L. I. (2015) Problems of medial supply of the Red Army during Great Patriotic War (accounts of Stalingrad medical doctors), Vest. Volgograd. Gosudar. Med. Univer. , 53 , 86-88.

Google Scholar

Silva, M. (2018) From Bombay to Rio de Janeiro: the circulation of knowledge and the establishment of the Manguinhos laboratory, 1894-1902, Hist. Cienc. Saude Manguinhos , 25 , 639-657, doi: https://doi.org/10.1590/S0104-59702018000400003 .

URL: http://www.samoupravlenie.ru/37-10.php .

Van Kammen, A. (1999) Beijerinck’s contribution to the virus concept – an introduction, Arch. Virol. Suppl. , 15 , 1-8, doi: https://doi.org/10.1007/978-3-7091-6425-9_1 .

Article CAS PubMed Google Scholar

Summers, W. C. (1991) From culture as organism to organism as cell: historical origins of bacterial genetics, J. Hist. Biol. , 24 , 171-190, doi: https://doi.org/10.1007/BF00209428 .

Ivanovski, D. (1892) Über die mosaikkrankheit der tabakspflanze, Bulletin scientifique publié par l’Académie impériale des sciences de Saint-Pétersbourg , 35 , 67-70.

Loeffler, F., and Frosch, P. (1898) Report of the commission for research on foot-and-mouth disease, Zent. Bakt. Parasitkde. Abt. I , 23 , 371-391.

Ivanovski, D. I. (1892) Tobacco mosaic disease, Trudy Varshavskogo Universiteta , 6 , 49-72.

Zhirnov, O. P., and Georgiev, G. P. (2017) D. I. Ivanovsky – a pioneer discover of viruses, as a new form of biological life, Ann. Russ. Acad. Med. Sci. , 72 , 84-86.

Article Google Scholar

Los, M., Czyz, A., Sell, E., Wegrzyn, A., Neubauer, P., and Wegrzyn, G. (2004) Bacteriophage contamination: is there a simple method to reduce its deleterious effects in laboratory cultures and biotechnological factories? J. Appl. Genet. , 45 , 111-120.

PubMed Google Scholar

Abedon, S. T., Thomas-Abedon, C., Thomas, A., and Mazure, H. (2011) Bacteriophage prehistory: is or is not Hankin, 1896, a phage reference? Bacteriophage , 1 , 174-178, doi: https://doi.org/10.4161/bact.1.3.16591 .

Hankin, E. H. (1896) The bactericidal action of the waters of the Jamuna and Ganges rivers on Cholera microbes, Ann. Inst. Pasteur , 10 , 511-523.

Gamaleya, N. F. (1898), Bacteriolysins – enzymes distroying bacteria, Russ. Arkhiv Patologii , pp. 607-613.

Bardell, D. (1982) An 1898 report by Gamaleya for a lytic agent specific for Bacillus anthracis, J. Hist. Med. Allied Sci. , 37 , 222-225, doi: https://doi.org/10.1093/jhmas/xxxvii.2.222 .

Thomas, G. H. (2014) Frederick William Twort: Not just Bacteriophage , in Microbiology Society.

Twort, F. W. (1915) An investigation on the nature of ultra-microscopic viruses, Lancet , 186 , 1241-1243.

Kunin, E. V. (2017) Logics of a Chance. On Nature and Development of Biological Evolution , ZAO Tsentropoligraf, Moscow.

Twort, F. W. (1936) Further investigations on the nature of ultra-microscopic viruses and their cultivation, J. Hyg. (Lond) , 36 , 204-235, doi: https://doi.org/10.1017/s0022172400043606 .

Article CAS Google Scholar

Dublanchet, A. (2017) Autobiographie de Félix d’Hérelle. Les pérégrinations d’un bactériologiste , Lavoisier, Paris.

Summers, W. C. (2016) Felix Hubert d’Herelle (1873-1949): history of a scientific mind, Bacteriophage , 6 , e1270090, doi: https://doi.org/10.1080/21597081.2016.1270090 .

D’Hérelle, F. (2007) On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D’Herelle, presented by Mr. Roux. 1917, Res. Microbiol. , 158 , 553, doi: https://doi.org/10.1016/j.resmic.2007.07.005 .

D’Hérelle, F. (1921) Le bactériophage; son rôle dans l’immunité , Masson et cie, Paris.

D’Hérelle, F. (1926) Bacteriophage and Its Significance for Imuunity , Gosudarstvennoye Izdatelstvo, Moscow-Leningrad.

D’Hérelle, F. (1931) An address on bacteriophagy and recovery from infectious diseases, Can. Med. Assoc. J. , 24 , 619-628.

PubMed PubMed Central Google Scholar

Schmalstieg, F. C., Jr., and Goldman, A. S. (2009) Jules Bordet (1870-1961): a bridge between early and modern immunology, J. Med. Biogr. , 17 , 217-224, doi: https://doi.org/10.1258/jmb.2009.009061 .

D’Hérelle, F., and Smith, G. H. (1926) The Bacteriophage and Its Behavior , The Williams & Wilkins Company, p. 629.

Billiau, A. (2016) At the centennial of the bacteriophage: reviving the overlooked contribution of a forgotten pioneer, Richard Bruynoghe (1881-1957), J. Hist. Biol. , 49 , 559-580, doi: https://doi.org/10.1007/s10739-015-9429-0 .

Gratia, A. (1921) Studies on the d’Herelle phenomenon, J. Exp. Med. , 34 , 115-126, doi: https://doi.org/10.1084/jem.34.1.115 .

Article CAS PubMed PubMed Central Google Scholar

Bordet, J., and Ciuca, M. (1921) Remarques sur l’historique des recherches concernant la lyse microbienne transmissible, Compt. Rend. Soc. Biol. , 84 , 745-747.

McKinley, E. B. (1925) Sérum antilytique obtenu par immunisation contre une bactérie normale, Compt. Rend. Soc. Biol. , 93 , 1050-1052.

Northrop, J. H., and Krueger, A. P. (1932) The role of intracellular bacteriophage in lysis of susceptible staphylococci, J. Gen. Physiol. , 15 , 329-332, doi: https://doi.org/10.1085/jgp.15.3.329 .

Northrop, J. H. (1937) Chemical nature and mode of formation of pepsin, trypsin and bacteriophage, Science , 86 , 479-483, doi: https://doi.org/10.1126/science.86.2239.479 .

Bordet, J. B. V. (1931) Croonian Lecture. – The theories of the bacteriophage, Proc. R. Soc. Ser. B , 107 , 398-417, doi: https://doi.org/10.1098/rspb.1931.0005 .

Appelmans, R. (1921) Le dosage du bactériophage, Compt. Rend. Soc. Biol. , 85 , 701.

Gratia, J.-P. (2000) Andre Gratia: a forerunner in microbial and viral genetics, Genetics , 156 , 471-476.

CAS PubMed PubMed Central Google Scholar

Gratia, A. (1922) The Twort–d’Herelle phenomenon: II. Lysis and microbic variation, J. Exp. Med. , 35 , 287-302, doi: https://doi.org/10.1084/jem.35.3.287 .

Summers, W. C. (1991) On the origins of the science in Arrowsmith: Paul de Kruif, Felix d’Herelle, and phage, J. Hist. Med. Allied Sci. , 46 , 315-332, doi: https://doi.org/10.1093/jhmas/46.3.315 .

Gratia, A. (1936) Des relations numeriques entre bacteries lysogènes et particules de bactériophage, Ann. Inst. Pasteur , 57 , 652-676.

Muller, H. J. (1922) Variation due to change in the individual gene, Am. Naturalist , 56 , 32-50.

Summers, W. C. (1993) How bacteriophage came to be used by the Phage Group, J. Hist. Biol. , 26 , 255-267, doi: https://doi.org/10.1007/Bf01061969 .

Schlesinger, M. (1934) Zur frage der chemischen zusammensetzung des bakteriophagen, Biochem. Z. , 273 , 306.

CAS Google Scholar

Grafe, A. (1991) A History of Experimental Virology , Springer-Verlag, Berlin, New York.

Ruska, H. (1940) Die Sichtbarmachung der bakteriophagen lyse im Übermikroskop, Naturwissenschaften , 28 , 45-46.

Kruger, D. H., Schneck, P., and Gelderblom, H. R. (2000) Helmut Ruska and the visualisation of viruses, Lancet , 355 , 1713-1717, doi: https://doi.org/10.1016/s0140-6736(00)02250-9 .

Kirchhelle, C. (2019) The forgotten typers: the rise and fall of Weimar bacteriophage-typing (1921-1935), Notes Records , doi: https://doi.org/10.1098/rsnr.2019.0020 .

Lwoff, A. (1953) Lysogeny, Bacteriol. Rev. , 17 , 269-337.

Otto, R., and Munter, H. (1921) Zum d’Herelleschen Phänomen, Dtsch. Med. Wchnschrft , 47 , 1579.

Otto, R., and Munter, H. (1923) Weitere untersuchungen zum d’Herelleschen Phänomen, 100 , 402-415.

Bail, O. (1922) Elementarbakteriophagen des Shigabacillus, Wien. Klin. Wochenschr. , 35 , 722-724.

Gildmeister, E., and Herzberg, K. (1924) Zur theorie der bakteriophagen (d’Herelle Lysine). 6. Mitteilung über das d’Herellesche phanomen, Zentr Bakteriol Parasitenk I Abt. Orig. , 93 , 402-420.

Bail, O. (1925) Der Kolistamm 88 von Gildemeister und Herzberg, Med. Klein. , 21 , 1271-1273.

Bordet, J. (1925) Le problème de lautolyse microbienne transmissible ou du bactériophage, Annales de l’Institut Pasteur , 1-47.

Bordet, J., and Renaux, E. (1928) L’autolyse bacterienne transmissible ou le bacteriophage, Ann. Inst. Pasteur , 42 , 1283.

Burnet, F. M., and McKie, M. (1929) Observations on a permanently lysogenic strain of B. enteritidis gaertner, Australian J. Exp. Biol. Med. Sci. , 6 , 277-284.

Sankaran, N. (2010) The bacteriophage, its role in immunology: how Macfarlane Burnet’s phage research shaped his scientific style, Stud. Hist. Philos. Biol. Biomed. Sci. , 41 , 367-375, doi: https://doi.org/10.1016/j.shpsc.2010.10.012 .

Burnet, F. M. (1934) The bacteriophages, Biol. Rev. , 9 , 332-350.

Dooren de Jong, E. D. (1931) Studien über Bakteriophagie. I. Über Bac. megatherium und den darin anwesenden Bakteriophagen, Zentralbl. Bakter. Parasitenkund. Abt. I. Orig. , 120 .

Wollman, E. (1928) Bactériophagie et processus similaires. Hérédité ou infection, Bull. Inst. Pasteur , 26 , 1-14.

Wollman, E. (1934) Bactériophagie (autolyse hérédocontagieuse) et bactériophages (facteurs lysogènes), Bull. Inst. Pasteur , 32 , 945-955.

Wollman, E., and Wollman, E. (1936) Régénération des bactériophages chez le B. megatherium lysogène, CR Soc. Biol. , 122 , 190-192.

Wollman, E., and Wollman, E. (1937) Les phases de bacteriophages (facteurs lysogènes), CR Soc. Biol. , 124 , 931-934.

Lwoff, A., and Gutmann, A. (1950) Recherches sur un Bacillus megatherium lysogene, Ann. Inst. Pasteur (Paris) , 78 , 711-739.

Lwoff, A., Siminovitch, L., and Kjeldgaard, N. (1950) Induction of the production of bacteriophages in lysogenic bacteria, Ann. Inst. Pasteur (Paris) , 79 , 815-859.

Hershey, A. D. (1975) Fag Lyambda , Mir, Moscow, pp. 7-20.

Hershey, A. D. (1975) Fag Lyambda , Mir, Moscow, pp. 21-64.

Gottesman, M. E., and Weisberg, R. A. (2004) Little lambda, who made thee? Microbiol. Mol. Biol. Rev. , 68 , 796-813, doi: https://doi.org/10.1128/MMBR.68.4.796-813.2004 .

Hayes, W. (1980) Portraits of viruses: bacteriophage lambda, Intervirology , 13 , 133-153, doi: https://doi.org/10.1159/000149119 .

Casjens, S. R., and Hendrix, R. W. (2015) Bacteriophage lambda: early pioneer and still relevant, Virology , 479-480 , 310-330, doi: https://doi.org/10.1016/j.virol.2015.02.010 .

Lederberg, J., and Tatum, E. L. (1946) Gene recombination in Escherichia coli , Nature , 158 , 558, doi: https://doi.org/10.1038/158558a0 .

Lederberg, E. M. (1951) Lysogenicity in E. coli K-12, Genetics , 36 , 560-560.

Campbell, A. (2007) Phage integration and chromosome structure. A personal history, Annu. Rev. Genet. , 41 , 1-11, doi: https://doi.org/10.1146/annurev.genet.41.110306.130240 .

Lederberg, E. M., and Lederberg, J. (1953) Genetic studies of lysogenicity in Escherichia coli , Genetics , 38 , 51-64.

Wollman, E., and Jacob, F. (1957) Sur les processus de conjugaison et de recombinaison chez Escherichia coli . 2. La localisation chromosomique du prophage-gamma et les consequences genetiques de l’induction zygotique, Ann. Inst. Pasteur , 93 , 323-339.

Ptashne, M. (1967) Isolation of the lambda phage repressor, Proc. Natl. Acad. Sci. USA , 57 , 306-313, doi: https://doi.org/10.1073/pnas.57.2.306 .

Ptashne, M. (1986) A Genetic Switch. Gene Control and Phage Lambda , Cell Press & Blackwell Scientific Publications, Cambridge University Press.

Zinder, N. D. (1992) Forty years ago: the discovery of bacterial transduction, Genetics , 132 , 291-294.

Morse, M. L., Lederberg, E. M., and Lederberg, J. (1956) Transduction in Escherichia coli K-12, Genetics , 41 , 142-156.

Fruciano, D. E., and Bourne, S. (2007) Phage as an antimicrobial agent: d’Herelle’s heretical theories and their role in the decline of phage prophylaxis in the West, Can. J. Infect. Dis. Med. Microbiol. , 18 , 19-26, doi: https://doi.org/10.1155/2007/976850 .

Summers, W. C. (2012) The strange history of phage therapy, Bacteriophage , 2 , 130-133, doi: https://doi.org/10.4161/bact.20757 .

Summers, W. C. (2001) Bacteriophage therapy, Annu. Rev. Microbiol. , 55 , 437-451, doi: https://doi.org/10.1146/annurev.micro.55.1.437 .

Almeida, G. M. F., and Sundberg, L. R. (2020) The forgotten tale of Brazilian phage therapy, Lancet Infect. Dis. , 20 , e90-e101, doi: https://doi.org/10.1016/S1473-3099(20)30060-8 .

Myelnikov, D. (2018) An alternative cure: the adoption and survival of bacteriophage therapy in the USSR, 1922-1955, J. Hist. Med. Allied Sci. , 73 , 385-411, doi: https://doi.org/10.1093/jhmas/jry024 .

Gelman, D., Eisenkraft, A., Chanishvili, N., Nachman, D., Coppenhagem Glazer, S., and Hazan, R. (2018) The history and promising future of phage therapy in the military service, J. Trauma Acute Care Surg. , 85 , S18-S26, doi: https://doi.org/10.1097/TA.0000000000001809 .

Chanishvili, N. (2012) Phage therapy – history from Twort and d’Herelle through Soviet experience to current approaches, Adv. Virus Res. , 83 , 3-40, doi: https://doi.org/10.1016/B978-0-12-394438-2.00001-3 .

Zaffiri, L., Gardner, J., and Toledo-Pereyra, L. H. (2012) History of antibiotics. From Salvarsan to cephalosporins, J. Invest. Surg. , 25 , 67-77, doi: https://doi.org/10.3109/08941939.2012.664099 .

Summers, W. C. (1993) Cholera and plague in India: the bacteriophage inquiry of 1927-1936, J. Hist. Med. Allied Sci. , 48 , 275-301, doi: https://doi.org/10.1093/jhmas/48.3.275 .

D’Hérelle, F., and Malone, R. H. (1927) A preliminary report of work carried out by the cholera bacteriophage enquiry, Ind. Med. Gaz. , 62 , 614-616.

D’Hérelle, F. (1929) Studies upon asiatic cholera, Yale J. Biol. Med. , 1 , 195-219.

D’Hérelle, F. (1931) Bacteriophage as a treatment in acute medical and surgical infections, Bull. N Y Acad. Med. , 7 , 329-348.

Kuhl, S. J., and Mazure, H. (2011) D’Hérelle. Preparation of therapeutic bacteriophages, Appendix 1 from: Le Phénomène de la Guérison dans les maladies infectieuses : Masson et Cie, 1938, Paris–OCLC 5784382, Bacteriophage , doi: https://doi.org/10.4161/bact.1.2.15680 .

Eaton, M. D., and Bayne-Jones, S. (1934) Bacteriophage therapy: review of the principles and results of the use of bacteriophage in the treatment of infections, J. Am. Med. Assoc. , 103 , 1769-1776.

Krueger, A. P., and Scribner, E. J. (1941) The bacteriophage: its nature and its therapeutic use, J. Am. Med. Assoc. , 116 , 2269-2277.

Morton, H. E., and Engley, F. B., Jr. (1945) Dysentery bacteriophage. Review of the literature on its prophylactic and therapeutic uses in man and in experimental infections in animals, J. Am. Med. Assoc. , 127 , 584-591.

Kazarnovskaya, S. S. (1932) Bacteriophagy , Izdatelstvo Akademii Nauk, Leningrad.

Tsulukidze, A. (1941) Examples of Bacteriophage Use for War-Time Trauma , Grizmedizdat, Tbilisi.

Pokrovskaya, M. P., Kaganova, L. S., Morozenko, M. A., Bulgakova, and Skatsenko, E. E. (1941) Treatment of Wounds with Bacteriophage , Medgiz, Moscow-Leningrad.

Pavlova, L. I., Sumarokov, A. A., Solodovnikov, Yu. P., and Nikityuk, N. M. (1973) On the issue of using dysentry bacteriophage as a dystentry prophylactis measure (literature review), Zh. Mikrobiol. Epidem. Immunobiol. , 50 , 27-32.

Solodovnikov, Yu. P., Pavlova, L. I., Garnova, N. A., Nogteva, Yu. B., and Sotemsky, Yu. S. (1971) Prohylactic application of the dry polivalent dysentry bacteriophage with pectin in child care centers. Part 2. On estanblishing tactics and scheme of bacteriphage application under modern conditions, Zh. Mikrobiol. Epidem. Immunobiol. , 48 , 123-127.

Solodovnikov, Yu. P., Pavlova, L. I., Emel’anov, P. I., Garnova, N. A., Nogteva, Yu. B., Sotemsky, Yu. S., Bogdashich, O. M., and Arshinova, V. V. (1970) Prohylactic application of the dry polivalent dysentry bacteriophage with pectin in child care centers. Part 1. Results of strictly controlled epidemiological trial (Yaroslavl, 1968), Zh. Mikrobiol. Epidem. Immunobiol. , 47 , 131-137.

Jones, E. H., Letarov, A. V., and Clokie, M. (2020) Neat science in a messy world: the global impact of human behavior on phage therapy, past and present, PHAGE , 1 , 16-22.

Phage and the Origins of Molecular Biology (1966) (Cairns, J., Stent, G. S., and Watson, J. D., eds.) Cold Springs Harbor Laboratory Press, New York.

Fischer, E. P., and Lipson, C. (1988) Thinking About Science: Max Delbrück and the Origins of Molecular Biology , Norton, New York.

Ellis, E. L., and Delbruck, M. (1939) The growth of bacteriophage, J. Gen. Physiol. , 22 , 365-384, doi: https://doi.org/10.1085/jgp.22.3.365 .

Northrop, J. H. (1939) Increase in bacteriophage and gelatinase concentration in cultures of Bacillus megatherium , J. Gen. Physiol. , 23 , 59-79, doi: https://doi.org/10.1085/jgp.23.1.59 .

Delbrück, M. (1940) Adsorption of bacteriophage under various physiological conditions of the host, J. Gen. Physiol. , 23 , 631-642, doi: https://doi.org/10.1085/jgp.23.5.631 .

Delbrück, M. (1945) Effects of specific antisera on the growth of bacterial viruses (bacteriophages), J. Bacteriol. , 50 , 137-150.

Delbrück, M. (1940) The growth of bacteriophage and lysis of the host, J. Gen. Physiol. , 23 , 643-660, doi: https://doi.org/10.1085/jgp.23.5.643 .

Luria, S. E., and Delbruck, M. (1943) Mutations of bacteria from virus sensitivity to virus resistance, Genetics , 28 , 491-511.

Newcombe, H. B. (1949) Origin of bacterial variants, Nature , 164 , 150, doi: https://doi.org/10.1038/164150a0 .

Luria, S. E., and Anderson, T. F. (1942) The identification and characterization of bacteriophages with the electron microscope, Proc. Natl. Acad. Sci. USA , 28 , 127-130, doi: https://doi.org/10.1073/pnas.28.4.127 .

Luria, S. E., and Latarjet, R. (1947) Ultraviolet irradiation of bacteriophage during intracellular growth, J. Bacteriol. , 53 , 149-163.

Avery, O. T., Macleod, C. M., and McCarty, M. (1944) Studies on the chemical nature of the substance inducing transformation of pneumococcal types: induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III, J. Exp. Med. , 79 , 137-158, doi: https://doi.org/10.1084/jem.79.2.137 .

Doermann, A. H. (1952) The intracellular growth of bacteriophages. I. Liberation of intracellular bacteriophage T4 by premature lysis with another phage or with cyanide, J. Gen. Physiol. , 35 , 645-656, doi: https://doi.org/10.1085/jgp.35.4.645 .

Anderson, T. F., and Doermann, A. H. (1952) The intracellular growth of bacteriophages. II. The growth of T3 studied by sonic disintegration and by T6-cyanide lysis of infected cells, J. Gen. Physiol. , 35 , 657-667, doi: https://doi.org/10.1085/jgp.35.4.657 .

Séchaud, J., and Kellenberger, E. (1956) Lyse précoce, provoquée par le chloroforme, chez les bactéries infectées par du bactériophage, Ann. Inst. Pasteur (Paris) , 90 , 102-106.

Delbrück, M. (1945) Interference between bacterial viruses; the mutual exclusion effect and the depressor effect, J. Bacteriol. , 50 , 151-170.

Delbrück, M., and Bailey, W. T. (1946) Induced mutations in bacterial viruses, Cold Spring Harbor Symposia on Quantitative Biology , 11 , 33-37.

Hershey, A. D. (1946) Mutation of bacteriophage with respect to type of plaque, Genetics , 31 , 620-640.

Luria, S. E. (1945) Mutations of bacterial viruses affecting their host range, Genetics , 30 , 84-99.

Luria, S. E. (1948) Sex in bacteria and viruses, Sci. Mon. , 66 , 159-162.

CAS PubMed Google Scholar

Luria, S. E. (1947) Reactivation of ultraviolet-inactivated bacteriophage particles inside double-infected host cells, J. Bacteriol. , 54 , 79.

Hershey, A. D., and Rotman, R. (1949) Genetic recombination between host-range and plaque-type mutants of bacteriophage in single bacterial cells, Genetics , 34 , 44-71.

Benzer, S. (1955) Fine structure of a genetic region in bacteriophage, Proc. Natl. Acad. Sci. USA , 41 , 344-354, doi: https://doi.org/10.1073/pnas.41.6.344 .

Crick, F. H., Barnett, L., Brenner, S., and Watts-Tobin, R. J. (1961) General nature of the genetic code for proteins, Nature , 192 , 1227-1232, doi: https://doi.org/10.1038/1921227a0 .

Hershey, A. D., and Chase, M. (1952) Independent functions of viral protein and nucleic acid in growth of bacteriophage, J. Gen. Physiol. , 36 , 39-56, doi: https://doi.org/10.1085/jgp.36.1.39 .

Salmond, G. P., and Fineran, P. C. (2015) A century of the phage: past, present and future, Nat. Rev. Microbiol. , 13 , 777-786, doi: https://doi.org/10.1038/nrmicro3564 .

Sanger, F., Air, G. M., Barrell, B. G., Brown, N. L., Coulson, A. R., Fiddes, C. A., Hutchison, C. A., Slocombe, P. M., and Smith, M. (1977) Nucleotide sequence of bacteriophage phi X 174 DNA, Nature , 265 , 687-695, doi: https://doi.org/10.1038/265687a0 .

Barderas, R., and Benito-Pena, E. (2019) The 2018 Nobel Prize in chemistry: phage display of peptides and antibodies, Anal. Bioanal. Chem. , 411 , 2475-2479, doi: https://doi.org/10.1007/s00216-019-01714-4 .

Calendar, R. (2006) The Bacteriophages , 2 Edn., Oxford University Press, p. 746.

Weinbauer, M. G. (2004) Ecology of prokaryotic viruses, FEMS Microbiol. Rev. , 28 , 127-181, doi: https://doi.org/10.1016/j.femsre.2003.08.001 .

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The author is grateful to E. E. Kulikov for invaluable comments and help in the preparation of this manuscript.

This work was supported by the Russian Foundation for Basic Research (project no. 19-14-50503).

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A. V. Letarov

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Letarov, A.V. History of Early Bacteriophage Research and Emergence of Key Concepts in Virology. Biochemistry Moscow 85 , 1093–1112 (2020). https://doi.org/10.1134/S0006297920090096

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v.202(2); 2016 Feb

Pick Your Poisson: An Educational Primer for Luria and Delbrück’s Classic Paper

The origin of beneficial mutations is fundamentally important in understanding the processes by which natural selection works. Using phage-resistant mutants in Escherichia coli as their model for identifying the origin of beneficial mutations, Luria and Delbrück distinguished between two different hypotheses. Under the first hypothesis, which they termed “acquired immunity,” the phages induced bacteria to mutate to immunity; this predicts that none of the resistant mutants were present before infection by the phages. Under the second hypothesis, termed “mutation to immunity,” resistant bacteria arose from random mutations independent of the presence of the phages; this predicts that resistant bacteria were present in the population before infection by the phages. These two hypotheses could be distinguished by calculating the frequencies at which resistant mutants arose in separate cultures infected at the same time and comparing these frequencies to the theoretical results under each model. The data clearly show that mutations arise at a frequency that is independent of the presence of the phages. By inference, natural selection reveals the genetic variation that is present in a population rather than inducing or causing this variation.

One of the seminal experiments in the history of genetics owes part of its inspiration to the presence of slot machines at a faculty mixer at the University of Indiana in 1942 ( Luria and Delbrück 1943 ). Salvador Luria himself described this experience in an essay in Phage and the Origins of Molecular Biology , a volume of essays dedicated to Luria’s coauthor, Max Delbrück, for Delbrück’s sixtieth birthday ( Luria 1966 ), and used the experience for the title of his autobiography as well ( Luria 1984 ). Luria’s essay provides an informative and personal background to this experiment and to the thought processes of the authors, as well as to the nature of scientific collaboration 75 years ago ( Luria 1966 ).

A slot machine has a very low probability of a payout during any single spin, but when the payout occurs, it is a jackpot. While not many people would have recognized the statistical underpinnings of slot machines and applied them to the origins of mutations in bacteria, Luria did. Luria had been working with Delbrück on several different biological questions related to viral or phage infections in bacteria sporadically over the preceding two years, but they had also been discussing experiments that could measure the rate at which new mutations arose in bacteria. In a letter to Delbrück in January 1943, Luria outlined the subsequent experiments almost precisely, and Delbrück responded immediately, also recognizing the implications. While waiting for the summer to conduct the experiments together at Cold Spring Harbor Laboratories, Delbrück worked out the theoretical aspects of what they could expect under different hypotheses. The result of that collaboration is “ Mutations of Bacteria from Virus Sensitivity to Virus Resistance ,” which appeared in Genetics in November of 1943 ( Luria and Delbrück 1943 ).

While bacteriophages ( i.e. , viruses that infect bacteria) were instrumental in the early days of molecular genetics, few modern students are likely to have much experience in working with them, so a brief experimental background is in order. A bacterial culture growing in nutrient broth is cloudy. When an aliquot of phages in excess of the number of bacteria is added to the culture, the culture clears because the phages are infecting and then lysing the bacterial cells as the phages reproduce. After a time of continued incubation, the culture becomes cloudy again because phage-resistant bacterial cells proliferate. This growth of virus-resistant bacteria after infection was referred to as secondary growth . The resistant cells could be isolated and grown as pure cultures and continued to exhibit phage resistance over subsequent generations. The resistance after the initial infection also did not depend on the continued presence of the phages, so change to resistance was heritable and stable. The same result occurs when an excess of phages is spread onto an agar plate before the bacteria are plated; most bacteria lyse, but after a time, a few resistant bacterial colonies appear.

Two models were proposed for the origins of these resistant cells in the phage-infected cultures. (While the paper clearly lays out the two models and their predictions, it does not always list them in the same order.) The fundamental question was this: does the phage infection directly induce the bacteria to mutate to resistance, or does the phage infection reveal the presence of preexisting resistant mutants in the culture? The first of these hypotheses is called acquired immunity , while the second is called mutation to immunity .

While there had been a few previous experiments to distinguish between these ideas, Luria and Delbrück wrote, “Neither of these views seems to have been rigorously proved in any single instance.” Interpretation of the results depended in large part on the rates at which spontaneous mutations arose in bacteria. This rate was unknown. Previous attempts to measure the mutation rate had been frustrated by highly variable results, and the lack of reproducible results in these experiments was seen as a significant shortcoming. Part of the genius of Luria and Delbrück was to realize that the fluctuation in previous results was inherent in the underlying question of bacterial variation; rather than being a problem for understanding the origins of mutations, fluctuations in the rates at which resistant mutants arise could help to provide the solution. Their experiment is often referred to as the fluctuation test because of this insight.

A few other points are important to recognize as we begin to discuss their results. Phage reproduction and lysis of the cell occur by a burst rather than slowly over time. Thus, mutation to resistance is a binary event that could be treated by binomial statistics. Delbrück trained as a physicist, and although Luria trained as a physician and microbiologist, he had spent a year studying physics at the University of Rome. This training allowed them to recognize that the occurrence of mutations follows a Poisson distribution, a probability distribution familiar to physicists but not so familiar to most biologists. Because a Poisson distribution is the occurrence of an event during a particular time interval, Luria and Delbrück also realized that for bacteria growing in culture, an appropriate measure of time intervals is the number of cell divisions. In addition to their quantitative backgrounds, Luria had the necessary background in microbiology to work with phages. Rather than work with an isolated mixture of different phages, Luria had pure cultures of the phage and had developed reliable methods for working with them. In the paper, the phage is referred to as α; it was subsequently renamed T1. (In his essay, Luria says that he named it α because his typewriter keyboard had such a key, so it was easy to type.)

The key experiment and its results

The basic procedure for the experiment was as follows: a broth culture of Escherichia coli B was grown from a small number of cells. Meanwhile, the phages were plated and spread over the surface of an agar plate with complete medium in numbers in excess of the number of bacteria to be plated. A suspension of the bacteria was then seeded onto the plates. Most of the bacteria lysed, but after a day or two, colonies of resistant bacteria were found on the plate and could be counted.

In a control experiment, 10 samples were taken from the same bacterial broth culture, with the results from three separate experiments shown in their Table 1 . Each sample was shown as a row in the table, while the columns showed different cultures. The reproducibility of their plating methods, which is essential to interpreting the fluctuation in results with the experiment cases, can be seen from a comparison of the results from the 10 samples in one experiment. The three cultures had different average numbers of resistant colonies, but the key parameters can be found by comparing the results for different samples from the same culture. We will discuss the implications of these results later.

The experimental cases to determine the origin of the resistant bacteria followed essentially the same protocol for growing the bacteria and plating them on an excess of phages. The key difference was that rather than taking samples from the same culture to plate, 9–20 different cultures were grown separately and plated at the same time. Thus, in their Table 2 , the columns are a series of individual cultures grown at the same time, while the rows are each a separate culture.

Much more of the paper is devoted to calculating the mutation rate and comparing it to expected values. While I will briefly discuss the importance of this result, it is probably sufficient to look at their Table 4 . The estimated mutation rate to resistance was 2.45 × 10 −8 per bacterium per division cycle. Separate experiments and slightly different methods and assumptions give essentially the same rate. The most important conclusion here is that their method to measure the mutation rate, for example, by calculating based on the number of divisions, did not show the variation that had been found by others, supporting the validity of their theoretical treatment.

Unpacking the Work

The poisson distribution and tables 1 and 2.

For students with experience in statistics and probability, the importance of the results in Tables 1 and 2 may not be so difficult to understand. For students with less background in statistics and probability, these results need to be unpacked and analyzed. After all, they constitute strong evidence that mutations arise at random without regard to their selective advantage or disadvantage, which is a key tenet of evolutionary theory. Let’s look at these data more closely.

Many events we encounter in genetics have two discrete outcomes: peas are wrinkled or round, flies have red or white eyes, and a mutation has occurred or it has not, for example. The frequencies of these two outcomes will follow some binomial probability distribution. (Many introductory statistics classes focus on events that have a continuous set of outcomes, with a probability distribution that follows a curve such as a Gaussian distribution rather than a binomial distribution.) A familiar nongenetics example of a binominal probability distribution is a coin flip: heads and tails are two discrete outcomes, and the probability of each is 0.5 on any single flip. One type of binomial distribution is the Poisson distribution, which expresses the probability of a given number of occurrences of an event that occurs during a fixed time period. Perhaps it is simpler to express this as a question: if we know that some event occurs at a particular rate, what is the probability that we will find x occurrences in the next hour (or some other time interval)? One of the most famous applications of the Poisson distribution involved the number of soldiers in the Prussian army killed per year by horse kicks, but a more familiar example is radioactive decay in a given time period. The Poisson distribution is particularly appropriate when one of the two outcomes is rare compared to the other, which is true in the case of resistance mutations. Most of the bacterial cells do not mutate to resistance in the next cell division, just as most radioactive atoms do not undergo radioactive decay and most Prussian soldiers did not die from a horse kick during a year.

As with other probability distributions, a Poisson distribution is defined by two parameters—the mean and the variance. The mean is the “average” number of colonies appearing on a plate, while the variance is calculated from the differences between each observation and the mean. A key defining feature for events that follow a Poisson distribution is that the mean and the variance are equal. Thus, we need to look at the variances in Tables 1 and 2 and compare them to the mean.

Notice in Table 1 that the mean for each experiment is nearly the same as the variance. The parameter P gives the probability that the amount of variation observed could arise by chance given this mean and variance, and the P -values are quite high for all three of the experiments. In other words, the results in Table 1 agree with expectations when a large population is sampled repeatedly for an event that occurs rarely.

We can now turn to Table 2 , in which the results are quite different. Look, for example, at the 20 cultures in experiment 16. While the average (mean) per sample is 11.35 resistant colonies, none of the individual cultures had close to this number of resistant colonies. In fact, 11 of the 20 cultures had no resistant colonies, and six more cultures had six or fewer colonies. However, three cultures had many more resistant colonies—from 35 to 107. These are Luria’s “jackpots.” A simple visual inspection of the data suggests that the 10 cultures in this experiment must not be separate samples from the same large population. While a visual inspection is helpful, calculation of the variance is more meaningful for drawing conclusions. Note that the variance is much larger than the mean in every experiment, so these results cannot be explained by assuming a Poisson distribution. Clearly, these cultures do not represent different samples from the same large population but instead show that mutations to resistance arise (or not) independently in every sample.

Let’s think about this result and the two hypotheses about the origin of resistant mutations. If the acquired-immunity hypothesis were correct, separate samples should have approximately the same mean number of resistant colonies, and the variance would be equal to the mean. Although the 20 samples in experiment 16 were grown separately, the phages were introduced at the same time in each sample, so if the phages are inducing mutation to resistance, the results should resemble those in Table 1 This hypothesis does not account for the results in Table 2 . However, under the mutation-to-immunity hypothesis, each separate culture mutates to immunity independently of when the phages are applied. By chance, some cultures will have no cells that mutate to immunity, even though the phages have been applied. Other cultures will have cells that mutate to immunity a few cell divisions before being plated and will have only a few resistant colonies. However, a few cultures will have cells that mutated to immunity early in the growth phase, so these cultures will have many resistant colonies.

Mutation rates

While Tables 1 and 2 present the most important results in the paper for understanding the origin of beneficial resistant mutations, it is worth looking at the data more fully to illustrate some other features of the experiment. The general equation for a Poisson distribution is

where x is any given number, and h is the number of mutation hits. From this, the probability that a culture will have no hits (that is, x = 0) is

By taking the natural log and multiplying by −1, h = −ln P 0 . The number of mutations can be calculated directly from the number of cultures that have no mutations.

In experiment 16 cited earlier, 11 of 20 (0.55) cultures had no hits, so h = −ln(0.55) = 0.60 mutations per culture. Because the number of cell divisions in each culture was known and the number of bacteria was known (5.6 × 10 8 in this experiment), the mutation rate per cell division can be easily computed by dividing the number of mutations per culture by the number of cells in the culture. Similar rates were found for every culture.

The genetic basis for resistance was not known at the time of these experiments. Subsequent analysis indicates that the mutation to resistance probably occurred in the fhuA gene of E. coli , which acts as the receptor for the T1 phage. It is not straightforward to compare these rates to more modern methods to estimate mutation rates, which arrive at estimates of about 10 −8 per base pair per generation.

Connections to Genetic Concepts

The most important connection that this makes to a key genetic concept—in fact, the key genetic concept that this paper demonstrated—is that mutations occur at random with respect to selective pressure. How does variation arise in a population, and what happens to it over time?

Mutations do not arise because they are beneficial to the organism. Mutations arise at random. Some will prove to be beneficial when a selective agent is applied, but selection does not produce the beneficial mutation. This is such a key concept that it may be taken for granted, but we take it for granted only because Luria and Delbrück demonstrated it to be true.

Suggestions for Classroom Use

Much of the theoretical background is difficult to understand unless a reader is well versed in differential equations. Fortunately, the most important concepts that the paper demonstrates do not require advanced courses in mathematics and statistics. But other important aspects of the experiment also should not be overlooked.

Detailed questions

The goal of these questions is to stimulate you to think about the design of the experiment, some of the assumptions that were made, and some key insights used in the techniques.

What is the assumption that was made to connect the occurrence of mutations to the number of cell divisions?
Based on what we now know about the mechanisms by which many mutations arise, why was this such an important assumption? In other words, by using cell division as their measure of time intervals, they were (consciously or unconsciously) connecting the occurrence of mutations to what other cellular process?
Luria and Delbrück made the point that the resistant bacteria that arose during secondary growth continued to be resistant even when grown in the absence of phages. Why is this so important?
Why is it important that pure cultures of the phages were used rather than mixed cultures, as some of the previous investigators had done?
What other very familiar and significant set of experiments in the history of genetics likewise relied on having “pure” cultures rather than a mixture?
Why was it important that the number of phages was in excess of the number of bacteria?
The various experiments reported in Tables 1 and 2 resulted in different means for the number of resistant colonies. While the significance of the data lies in the comparison between the means and the variance for an experiment, what might be some reasons that different experiments would have different means?
Explain how the “jackpots” arose, with some speculation about what connection this made in Luria’s imagination. Or, to ask this another way, how does the fluctuation in the number of different resistant colonies from experiment to experiment, which was considered a significant problem for previous studies, provide insights into the events that occurred here?
What are some of the reasons that these different measures of mutation rate are hard to compare or that they cannot be compared?
What contemporary methods are used to measure the rate of spontaneous mutation?
What are some of the reasons that the rates of spontaneous mutation (measured by nucleotide per generation) are so similar in many different organisms?
The acquired-immunity hypothesis is essentially that cells acquire heritable characteristics in response to environmental conditions. While this is clearly not generally true, there may be some unusual circumstances in which this occurs. How does the CRISPR response of bacterial cells resemble acquired immunity?
Assuming that the probability of resistant “hits” is the same in each case and similar to what was observed by Luria and Delbrück, what would be the chance that resistance to three drugs would appear in a given small culture from your experiment? (This requires using the Poisson distribution.)
In fact, resistance to all three antibiotics occurs much more frequently than is predicted from your response to part a. What are some reasons that resistance to three antibiotics simultaneously might occur more often than predicted?

Literature Cited

Luria S. E., 1966. Mutations of bacteria and of bacteriophage , pp. 173–179 in Phage and the Origins of Molecular Biology , ed. by Cairns J., Stent G. S., Watson J. D. Cold Spring Harbor Press, Cold Spring Harbor, NY. [ Google Scholar ]
Luria S. E., 1984. A Slot Machine, a Broken Test Tube: An Autobiography . HarperCollins, New York. [ Google Scholar ]
Luria S. E., Delbrück M., 1943. Mutations of bacteria from virus sensitivity to virus resistance . Genetics 28 : 491–511. [ PMC free article ] [ PubMed ] [ Google Scholar ]

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one-step growth experiment

Quick reference.

The classic procedure that laid the foundation for the quantitative study of the life cycle of lytic bacterial viruses. A suspension of bacteria was mixed with enough viruses to ensure that a virus attached to each host cell. Free viruses were removed, and at periodic intervals thereafter aliquots were withdrawn and subjected to plaque assay (q.v.). The number of plaques per aliquot remained constant for an initial period of time. Aliquots taken after this latent period showed a progressive increase in plaque numbers. During this time, infected cells were lysing and liberating infectious phage, each capable of producing a plaque. Once all cells had lysed, a plateau was reached, and so the curve describing plaque counts during the experiment showed a single step. The eclipse period refers to the time between viral attachment and the assembly of the first progeny phage. It is during this period that replication and assembly of the phages is occurring. Cells must be artificially lysed to determine when the earliest infectious particles appear. The latent period is longer than the eclipse period because the host cell does not normally lyse until many progeny have been assembled. See Chronology, 1939, Ellis and Delbrück; burst size, plaque.

From: one-step growth experiment in A Dictionary of Genetics »

Subjects: Science and technology — Life Sciences

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One Step Growth Curve Experiment of Virus

One step growth experiment is An experiment by which molecular events that are occurring during reproduction of virus can be observed.

It reveals the fundamental nature of virus replication process.
This process was first performed by Ellis & Delbruck in 1939 by using T2 bacteriophages.
They also determined the plague counting method for the enumeration of bacteriophages.
In this experiment, only a single or one cycle of virus growth is observed.
Therefore, it is called as one step growth experiment.
Excess number of host cells are allowed to infect with phage particles.
This makes the infection synchronous. That means the simultaneous infection of large number of particles to the host cell is taking place.
Observation made on such host cell culture is similar to observation made on single host cell infected by a phage.
In the experiment, excess host cells are infected with phage particles at a ratio of 1:10.
This is done to prevent the adsorption of more than one virus per cell.
Mixture is incubated for a short period of time (5 min).
This incubation allows the adsorption of phage particle on host cell.
If the bacteria are in excess, all the phage particles will be adsorbed.
Such mixture is then diluted to such an extent (1:1000) that the virus particles released after first round of replication cannot adsorb to uninfected cell.
Thus, only one step of virus growth can occur.
Samples of diluted mixture are then removed at regular time interval & used for plaque count.
This gives a measure of infectious centers i.e. the infected bacteria & number of virus particles (i.e. No. of plaques per ml).
When a log no, of plague forming units/ml is potted against time, a curve is obtained & it is termed as one step growth curve .
This one step growth curve shows the various events that are occurring during the virus replication cycle.

• This curve gives three distinct phases - 1]. Latent Period 2]. Burst or Rise Period 3]. Plateau Period

One step growth curve of virus

I]. Latent Period:

It is the period from infection to cell lysis.
During this, there is no release of new virus particles from infected cells.
Therefore, the plaque count remains constant.
T phage has latent period of 22 to 23 min at 37°C.
This period can be divided into two phases as ' Eclipse ' period & ' Intracellular Accumulation ' period.
Time from infection until intracellular accumulation of phages is called as 'Eclipse' period.
T2 bacteriophage has eclipse period of about 11.5 min at 37°C.
In this, gene expression, protein synthesis & genome synthesis occurs.
The time from initiation to the end of intracellular accumulation of phages is called as 'Intracellular Accumulation' period.
During this, phage proteins & genomes assemble into new phage particles.
T2 bacteriophage requires the period of about 11 to 12 min. at 37° C for this period.

II]. Burst Period or Rise Period

The time from initiation of infected host cell lysis to the end is called rise or burst period .
At the end of latent period, each infected cell lyses & liberates a crop of new virus particles.
During this phase, there is release of new viral particles from infected cells & therefore, plaque count increases rapidly.
T2 bacteriophage has the rise period of about 10 min. at 37°C.
Due to the asynchrony of infection the rise period is slightly extended.

III] Plateau Period :

This period represents the end of all infected host cell lysis.
The newly liberated phage particles fail to meet uninfected host cells due to high dilution.
Therefore, during this phase, the plaque count remains constant.
T2 phage enters in plateau in about 30 min. at 37°C.
Burst Size - Burst size is defined as the number of virus particles produced from the infection of a single cell. The burst size is calculated using following formula -

T2 phage has a burst size of less than 100 phages/cell.
Burst size varies from 20 to 3000 virions/cell for different viruses.

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Practical Advice on the One-Step Growth Curve

Series: Methods In Molecular Biology > Book: Bacteriophages

Protocol | DOI: 10.1007/978-1-4939-7343-9_3

Department of Pathobiology, University of Guelph, Guelph, ON, Canada
Department of Food Science, University of Guelph, Guelph, ON, Canada
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada

The one-step growth experiment is fundamental to the description of a new bacteriophage. The following protocol is optimized for those working with rapidly growing bacterial cultures.

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Citations (95)

Related articles, a microtiter plate assay at acidic ph to identify potentiators that enhance pyrazinamide activity against mycobacterium tuberculosis, α-synuclein seeding assay using rt-quic, ultrasensitive rt-quic seed amplification assays for disease-associated tau, α-synuclein, and prion aggregates, cyanide measurements in bacterial culture and sputum, high-throughput and longitudinal analysis of aging and senescent decline in caenorhabditis elegans, tracking cell wall-anchored proteins in gram-positive bacteria, use of galleria mellonella as an animal model for studying the antimicrobial activity of bacteriophages with potential use in phage therapy, using the zebrafish larval model of infection to investigate antibiotic efficacy and combination treatments against staphylococcus aureus, quantification of phagocytosis using flow cytometry.

Ellis EL, Delbrück M (1939) The growth of bacteriophage. J Gen Physiol 22:365–384
Hyman P, Abedon ST (2009) Practical methods for determining phage growth parameters. Methods Mol Biol 501:175–202
Symonds ND (1968) Experiment 14 – One-step growth curve and the Doermann experiment. In: Clowes RC, Hayes W (eds) Experiments in microbial genetics. Blackwell, Oxford, pp 75–78
Kelln RA, Warren RA (1971) Isolation and properties of a bacteriophage lytic for a wide range of pseudomonads. Can J Microbiol 17:677–682
Kropinski AM (2009) Measurement of the rate of attachment of bacteriophage to cells. Methods Mol Biol 501:151–155

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THE GROWTH OF BACTERIOPHAGE

Affiliation.

1 William G. Kerckhoff Laboratories of the Biological Sciences, California Institute of Technology, Pasadena.
PMID: 19873108
PMCID: PMC2141994
DOI: 10.1085/jgp.22.3.365

1. An anti-Escherichia coli phage has been isolated and its behavior studied. 2. A plaque counting method for this phage is described, and shown to give a number of plaques which is proportional to the phage concentration. The number of plaques is shown to be independent of agar concentration, temperature of plate incubation, and concentration of the suspension of plating bacteria. 3. The efficiency of plating, i.e. the probability of plaque formation by a phage particle, depends somewhat on the culture of bacteria used for plating, and averages around 0.4. 4. Methods are described to avoid the inactivation of phage by substances in the fresh lysates. 5. The growth of phage can be divided into three periods: adsorption of the phage on the bacterium, growth upon or within the bacterium (latent period), and the release of the phage (burst). 6. The rate of adsorption of phage was found to be proportional to the concentration of phage and to the concentration of bacteria. The rate constant k(a) is 1.2 x 10(-9) cm.(8)/min. at 15 degrees C. and 1.9 x 10(-9) cm.(8)/min. at 25 degrees . 7. The average latent period varies with the temperature in the same way as the division period of the bacteria. 8. The latent period before a burst of individual infected bacteria varies under constant conditions between a minimal value and about twice this value. 9. The average latent period and the average burst size are neither increased nor decreased by a fourfold infection of the bacteria with phage. 10. The average burst size is independent of the temperature, and is about 60 phage particles per bacterium. 11. The individual bursts vary in size from a few particles to about 200. The same variability is found when the early bursts are measured separately, and when all the bursts are measured at a late time.

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COMMENTS

Replication
This is particularly true of virus replication. Two very significant experiments that illustrated the fundamental nature of viruses were performed on bacteriophages. The first of these was done by Ellis and Delbruck in 1939 and is usually referred to as the "single-burst" experiment or "one-step growth curve" (Figure 4.1). This was the ...
PDF One-step Phage Growth Curve I. Objectives Ii. Introduction
In this laboratory experiment, we shall attempt to repeat the Ellis-Delbruck experiment. There are a number of steps and manipulations to perform and you are cautioned to be deliberate in your technique. III. LABORATORY SUPPLIES Bacterial culture or host suspension 5 ml/group Phage lysate, 0.1 ml in small tt 1 tt/group Phage base plates 8/group
Phage group
However, as Ellis describes, Delbruck soon dispelled this initial reaction of disbelief by his own analysis of the phenomenon, and promptly joined in the work with enthusiasm, bringing to it his training in mathematics and physics, and intense interest in genetics. Their initial collaborative findings were published in 1939. ... This experiment ...
Luria-Delbrück experiment
Luria-Delbrück experiment. The two possibilities tested by the Luria-Delbrück experiment. (A) If mutations are induced by the media, roughly the same number of mutants are expected to appear on each plate. (B) If mutations arise spontaneously during cell divisions prior to plating, each plate will have a highly variable number of mutants.
Max Delbrück
Max collaborated with Ellis to investigate "The growth of bacteriophage" (Ellis and Delbrück 1939). This article describes the beginning of modern phage work: presenting one-step-growth curves and a way to determine the concentration of bacterial viruses in solution. It makes use of statistical arguments from physics, thereby creating a ...
History of Early Bacteriophage Research and Emergence of Key Concepts
Ellis showed Delbruck his experiments on the bacteriophage life cycle (first versions of the one-step growth experiments), which impressed Delbruck so much that he switched to work with bacteriophages together with Ellis. In 1939, they published the paper "The growth of bacteriophage" . This work went far beyond a simple one-step growth ...
How Bacteriophage Came to Be Used by the Phage Group
While Delbruck is often credited with "inventing" the so-called one-step growth experiment, Ellis noted that this result formed a cornerstone of d'Herelle's concept of phage multiplication: in d'Herelle's words, "the increase in the number of corpuscles does not take place in a continuous progressive fashion, but by succes-sive liberations."'"
One-Step Growth Experiment
One-Step Growth Experiment - How it all started. The development of the one-step growth experiment in 1939 by Max Delbrück and Emory Ellis marks the beginning of modern bacteriophage research. The experiment involves mixing a culture of susceptible bacteria such as E. coli with bacteriophage particles, and the phages are allowed a short ...
THE GROWTH OF BACTERIOPHAGE
The growth of phage can be divided into three periods: adsorption of the phage on the bacterium, growth upon or within the bacterium (latent period), and the release of the phage (burst). 6. The rate of adsorption of phage was found to be proportional to the concentration of phage and to the concentration of bacteria.
Pick Your Poisson: An Educational Primer for Luria and Delbrück's
Background. One of the seminal experiments in the history of genetics owes part of its inspiration to the presence of slot machines at a faculty mixer at the University of Indiana in 1942 (Luria and Delbrück 1943).Salvador Luria himself described this experience in an essay in Phage and the Origins of Molecular Biology, a volume of essays dedicated to Luria's coauthor, Max Delbrück, for ...
The Luria-Delbruck Experiment
explorebiology.orgSalvador Luria and Max Delbruck performed a Nobel Prize winning experiment to show that new mutations arise spontaneously, favoring Darwin'...
One-step growth experiment
one-step growth experiment. The classic procedure that laid the foundation for the quantitative study of the life cycle of lytic bacterial viruses. A suspension of bacteria was mixed with enough viruses to ensure that a virus attached to each host cell. Free viruses were removed, and at periodic intervals thereafter aliquots were withdrawn and ...
PDF Luria-Delbruck (1943) experiment
Luria-Delbruck (1943) experiment. S. E. Luria and M. Delbruck (1943). Mutations of bacteria from vrius sensitivity to virus resistance. Genetics 28:491. [Presented by: Steve Carr ([email protected]), 14 January 2014] Background. Max Delbruck (1906 -1981) & Salvador Luria (1912 -1991) Shared 1969 Nobel Prize in Physiology or Medicine.
One Step Growth Curve Experiment of Virus
One step growth experiment is An experiment by which molecular events that are occurring during reproduction of virus can be observed. It reveals the fundamental nature of virus replication process. This process was first performed by Ellis & Delbruck in 1939 by using T2 bacteriophages. They also determined the plague counting method for the ...
Luria-Delbrück, revisited: the classic experiment does not rule out
We re-examined data from the classic Luria-Delbrück fluctuation experiment, which is often credited with establishing a Darwinian basis for evolution. ... [25] Jones M, Thomas S and Rogers A 1994 Luria-Delbruck fluctuation experiments: design and analysis Genetics 136 1209-16. Go to reference in article; Google Scholar [26] Jaeger G and ...
Practical Advice on the One-Step Growth Curve
Ellis EL, Delbrück M (1939) The growth of bacteriophage. J Gen Physiol 22:365-384 Hyman P, Abedon ST (2009) Practical methods for determining phage growth parameters. Methods Mol Biol 501:175-202 Symonds ND (1968) Experiment 14 - One-step growth curve and the Doermann experiment.
Luria-Delbrück, revisited: the classic experiment does not rule out
The Luria-Delbrück paper also did not consider the possibility of neither model fitting the experiment. Using Bayesian model selection, we find that the Luria-Delbrück experiment, indeed, favors the Darwinian evolution over purely Lamarckian. However, our analysis does not rule out the combined model, and hence cannot rule out Lamarckian ...
THE GROWTH OF BACTERIOPHAGE
The growth of phage can be divided into three periods: adsorption of the phage on the bacterium, growth upon or within the bacterium (latent period), and the release of the phage (burst). 6. The rate of adsorption of phage was found to be proportional to the concentration of phage and to the concentration of bacteria.
PDF Founder of phage genetics
Fischer recounts that Delbruck's entry In 1937, for scientific rather than ideo- ... An Account of Max Delbruck, building another biologist, E.L. Ellis, was Pioneer of Molecular Biology ...
Viruses experiments
Notes virus experiements ellis and delbruck 1939 single burst experiment method bacteriophage particles added to culture of rapidly growing bacteria after few. Skip to document. University; High School. Books; ... Ellis and Delbruck 1939 - Single burst experiment Method 1. Bacteriophage particles added to culture of rapidly growing bacteria 2.
THE GROWTH OF BACTERIOPHAGE
5. The growth of phage can be divided into three periods: adsorption of the phage on the bacterium, growth upon or within the bacterium (latent period), and the release of the phage (burst). 6. The rate of adsorption of phage was found to be proportional to the concentration of phage and to the concentration of bacteria.
[PDF] THE GROWTH OF BACTERIOPHAGE
A plaque counting method is described, and shown to give a number of plaques which is proportional to the phage concentration, which is independent of agar concentration, temperature of plate incubation, and concentration of the suspension of plating bacteria. 1. An anti-Escherichia coli phage has been isolated and its behavior studied. 2. A plaque counting method for this phage is described ...
Luria-Delbruck, revisited: The classic experiment does not rule out
ogram, Emory University, Atlanta, GA 30322, USAE-mail: [email protected]. We re-examined data from the classic Luria-Delbruck uctua. ion experiment, which is often credited with establishing a Darwinian basis for evolution. We argue that, for the Lamarckian model of evolution to be ruled out by the experiment, the experiment must ...