In 1936, Frank Macfarlane Burnet published a paper entitled “Induced lysogenicity and the mutation of bacteriophage within lysogenic bacteria,” in which he demonstrated that the introduction of a specific bacteriophage into a bacterial strain consistently and repeatedly imparted a specific property – namely the resistance to a different phage – to the bacterial strain that was originally susceptible to lysis by that second phage. Burnet’s explanation for this change was that the first phage was causing a mutation in (...) the bacterium which rendered it and its successive generations of offspring resistant to lysogenicity. At the time, this idea was a novel one that needed compelling evidence to be accepted. While it is difficult for us today to conceive of mutations and genes outside the context of DNA as the physico-chemical basis of genes, in the mid 1930s, when this paper was published, DNA’s role as the carrier of hereditary information had not yet been discovered and genes and mutations were yet to acquire physical and chemical forms. Also, during that time genes were considered to exist only in organisms capable of sexual modes of replication and the status of bacteria and viruses as organisms capable of containing genes and manifesting mutations was still in question. Burnet’s paper counts among those pieces of work that helped dispel the notion that genes, inheritance and mutations were tied to an organism’s sexual status. In this paper, I analyze the implications of Burnet’s paper for the understanding of various concepts – such as “mutation,” and “gene,” – at the time it was published, and how those understandings shaped the development of the meanings of these terms and our modern conceptions thereof. (shrink)

In this paper I consider Kenneth Schaffner''s(1998) rendition of ''''developmentalism'''' from the point of viewof bacteriophage biology. I argue that the fact that a viablephage can be produced from purified DNA and host cellularcomponents lends some support to the anti-developmentalist, ifthey first show that one can draw a principled distinctionbetween genetic and environmental effects. The existence ofhost-controlled phage host range restriction supports thedevelopmentalist''s insistence on the parity of DNA andenvironment. However, in the case of bacteriophage, thedevelopmentalist stands on (...) less firm ground than when organismswith nervous systems, such as Schaffner''s C. elegans, areconsidered. (shrink)

The Australian scientist Frank Macfarlane Burnet—winner of the Nobel Prize in 1960 for his contributions to the understanding of immunological tolerance—is perhaps best recognized as one of the formulators of the clonal selection theory of antibody production, widely regarded as the ‘central dogma’ of modern immunology. His work in studies in animal virology, particularly the influenza virus, and rickettsial diseases is also well known. Somewhat less known and publicized is Burnet’s research on bacteriophages, which he conducted in the first decade (...) of his research career, immediately after completing medical school. For his part, Burnet made valuable contributions to the understanding of the nature of bacteriophages, a matter of considerable debate at the time he began his work. Reciprocally, it was while working on the phages that Burnet developed the scientific styles, the habits of mind and laboratory techniques and practices that characterized him for the rest of his career. Using evidence from Burnet’s published work, as well as personal papers from the period he worked on the phages, this paper demonstrates the direct impact that his experiments with phages had on the development of his characteristic scientific style and approaches, which manifested themselves in his later career and theories, and especially in his thinking regarding various immunological problems. (shrink)

Roots presents articles on major discoveries that laid the basis for contemporary molecular and cellular biology. In this article, Norton D. Zinder reviews the first findings about the single‐stranded DNA‐containing bacteriophages and what is known today about the genetics and molecular biology of these phages.

Graphical Abstract2015 marks the centennial of the discovery of bacteriophages, viruses that infect bacteria. Phages have been central to some of biology's most meaningful advances over the past hundred years (shown here); they greatly influence the workings of the biosphere, and are poised to play expanded roles in biomedicine, biotechnology, and ecology.

SummaryIn the 1940s a controversy developed between John H. Northrop (Nobel Laureate, 1946) and Max Delbrück (Nobel Laureate, 1969) on the formation of bacteriophage. From the historiography of molecular biology there emerges a picture of an obstinate Northrop who repudiated the ‘correct’ insights revealed by the experiments of Delbrück. The established reputation of Northrop confronts one with the question of why Delbrück's epoch-making experiments were not convincing for Northrop. It will be argued that this was a consequence of local (...) incommensurability between Northrop's physiological/chemical research style and Delbrück's bacteriological/genetic research style. The analysis of this controversy reveals the elements that made up these two research styles. (shrink)

College of Medicine, University of South Alabama Mobile, AL 36688-0002, USA wbp501{at}jaguar1.usouthal.edu ' + u + '@' + d + ' '//--> Abstract Recent work in viral genomics has shown that bacteriophages exhibit a high degree of mosaicism, which is most likely due to a long history of prolific horizontal gene transfer (HGT). Given these findings, we argue that each of the most plausible attempts to properly classify bacteriophages into distinct species fail. Mayr's biological species concept fails because there is (...) no useful viral analog to sexual reproduction. Phenetic species concepts fail because they obscure the mosaicism and the rich reticulated viral histories. Phylogenetic species concepts, even when extended to take into account reticulation, fail because there is no non-arbitrary distinction between recombination events that create a new viral species and those that do not. There is good reason to think that bacteriophages, arguably the Earth's most abundant biological agent, evolve without forming species. Introduction The Biology of Viruses 2.1 Bacteriophage life cycles 2.2 Mechanisms of HGT The Species Problem and Species Concepts 3.1 Phenetic species concepts 3.2 The biological species concept 3.3 Phylogenetic species concepts 3.4 The ecological species concept 3.5 Homeostatic property cluster species Viruses and Species Taxonomy Reticular Phylogenies Conclusion CiteULike Connotea Del.icio.us What's this? (shrink)

The year 2015 marks the 100th anniversary of a publication by William Twort, in which he first described lysis of bacterial cultures by a filterable, self-replicating agent. In 1917, Félix d’Herelle, coined the name “bacteriophage” for the proposed agent. Two Belgian teams of microbiologists were among the few to critically examine the nature of the bacteriophage at that time. Although their experimental results agreed, their interpretations did not. Richard Bruynoghe interpreted them as supportive of d’Herelle’s notion of an (...) ultramicroscopic microorganism. Jules Bordet found the proposal of a complex organism unnecessary and saw the bacteriophage as a simple endogenous bacterial enzyme endowed with capacity to induce its own secretion as well as ability to cause lysis of the bacteria. Two decades would elapse before bacteriophages were visualized and confirmed to be organized particles. However, by that time, Bruynoghe’s work, that had only been published in short notes in society proceedings, was virtually forgotten. The present paper revives his original observations and arguments, while also recognizing that Bordet’s alternative hypothesis had scientific merit. (shrink)

In order to explain several discrepancies between the gene-recombination phenomena in phages and in higher organisms, we assume that theT 2 phage, after entering the bacterium, divides in three parts corresponding to the three “chromosomes' whichHershey andRotman have traced in this phage. The three parts are supposed to be able to divide further by rupture or by the action of other “chromosome fragments”. Each fragment is supposed able to reproduce inside the bacterium as a more or less independent unit and (...) before lysis of the bacterium the various parts are assumed to reunite in complete sets of genes each forming a new phage.After discussing the experimental facts supporting these assumptions, we show that the assumptions are in perfect agreement with the theory of the symbiosis of genes, a theory which seems necessary in order to explain the ability of the “chromosome-fragments” to reunite into complete phages.Also the problems arising with respect to the sexual reproduction in bacteria is discussed under the point of view of the symbiosis theory. The assumption is made that the hereditary material is transduced from bacterium to bacterium by ultramicroscopic virus-like particles “genophores”. In several lysogenic bacteria the genophores are supposed still able to act as parasites instead of symbiontes towards some other sensitive bacteria. The experimental facts supporting this assumption are analyzed, and new experimental tests suggested. (shrink)

The Type VI secretion system is a multiprotein and mosaic apparatus that delivers protein effectors into prokaryotic or eukaryotic cells. Recent data on the enteroaggregative Escherichia coli T6SS have provided evidence that the TssA protein is a key component during T6SS biogenesis. The T6SS comprises a trans-envelope complex that docks the baseplate, a cytoplasmic complex that represents the assembly platform for the tail. The T6SS tail is structurally, evolutionarily and functionally similar to the contractile tails of bacteriophages. We have shown (...) that TssA docks to the membrane complex, recruits the baseplate complex and initiates and coordinates the polymerization of the inner tube with that of the sheath. Here, we review these recent findings, discuss the variations within TssA-like proteins, speculate on the role of EAEC TssA in T6SS biogenesis and propose future research perspectives. In the environment, bacteria have to cope with other microbial species and therefore have evolved anti-microbial mechanisms. The bacterial Type VI secretion system transports toxins into bacterial and/or eukaryotic cells using a contractile mechanism. At the architectural level, the T6SS could be viewed as a nano-speargun assembled in the bacterial cytoplasm and anchored to a trans-envelope complex. We describe and speculate on recent findings demonstrating that the TssA subunit is involved in the different stages of T6SS biogenesis. (shrink)

Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 and few other proteins encoded by Herpesviridae, Nef, E1A, NS5A, PB2, HN, L83L, (...) MC155R, other Poxviridae proteins, and some bacteriophages of human associated bacteria. If confirmed experimentally, these findings may aid in dissection of molecular functions of uncharacterized viral proteins and provide a novel rationale for statin and FT/GGT1-based inhibition of viral infections. Prenylation of bacteriophage proteins may aid in moderation of microbial infections. Many human viruses, including HCV, HIV1, ASFV, and a number of Adeno-, Pox-, and herpesviruses, including CMV, encode the substrates for mammalian prenylation enzymes. Prenylation is advantageous for viral infection; its suppression by FT/GGT and FPPS inhibitors has antiviral effects. In bacteriophages, prenylation may aid in moderation of microbial infections. (shrink)

Are bacteriophage T4 and the long-nosed elephant fish valuable in their own right? Nicholas Agar defends an affirmative answer to this question by arguing that anything living is intrinsically valuable. This claim challenges received ethical wisdom according to which only human beings are valuable in themselves. The resulting biocentric or life-centered morality forms the platform for an ethic of the environment. -/- Agar builds a bridge between the biological sciences and what he calls "folk" morality to arrive at a (...) workable environmental ethic and a new spectrum--a new hierarchy--of living organisms. The book overturns common-sense moral belief as well as centuries of philosophical speculation on the exclusive moral significance of humans. Spanning several fields, including philosophy of psychology, philosophy of science, and other areas of contemporary analytic philosophy, Agar analyzes and speaks to a wide array of historic and contemporary views, from Aristotle and Kant, to E. O. Wilson, Holmes Rolston II, and Baird Callicot. The result is a challenge to prevailing definitions of value and a call for a scientifically-informed appreciation of nature. (shrink)

This article shows how Lamarckism was essential in the birth of the French school of molecular biology. We argue that the concept of inheritance of acquired characters positively shaped debates surrounding bacteriophagy and lysogeny in the Pasteurian tradition during the interwar period. During this period the typical Lamarckian account of heredity treated it as the continuation of protoplasmic physiology in daughter cells. Félix d’Hérelle applied this conception to argue that there was only one species of bacteriophage and Jules Bordet (...) applied it to develop an account of bacteriophagy as a transmissible form of autolysis and to analyze the new phenomenon of lysogeny. In a long-standing controversy with Bordet, Eugène Wollman deployed a more morphological understanding of the inheritance of acquired characters, yielding a particulate, but still Lamarckian, account of lysogeny. We then turn to André Lwoff who, with several colleagues, completed Wollman’s research program from 1949 to 1953. We examine how he gradually set aside the Lamarckian background, finally removing inheritance of acquired characters from the resulting account of bacteriophagy and lysogeny. In the conclusion, we emphasize the complex dual role of Lamarckism as it moved from an assumed explanatory framework to a challenge that the nascent molecular biology had to overcome. (shrink)

Unlike the most well‐characterized prokaryotic polymerase, E. Coli DNA pol I, none of the eukaryotic polymerases have their own 5′ to 3′ exonuclease domain for nick translation and Okazaki fragment processing. In eukaryotes, FEN‐1 is an endo‐and exonuclease that carries out this function independently of the polymerase molecules. Only seven nucleases have been cloned from multicellular eukaryotic cells. Among these, FEN‐1 is intriguing because it has complex structural preferences; specifically, it cleaves at branched DNA structures. The cloning of FEN‐1 permitted (...) establishment of the first eukaryotic nuclease family, predicting that S. cerevisiae RAD2 (S. pombe Rad13) and its mammalian homolog, XPG, would have similar structural specficity. The FEN‐1 nuclease family includes several similar enzymes encoded by bacteriophages. The crystal structures of two enzymes in the FEN‐1 nuclease family have been solved and they provide a structural basis for the interesting steric requirements of FEN‐1 substrates. Because of their unique structural specificities, FEN‐1 and its family members have important roles in DNA replication, repair and, potentially, recombination. Recently, FEN‐1 was found to specifically associate with PCNA, explaining some aspects of FEN‐1 function during DNA replication and potentially in DNA repair. (shrink)

Antimicrobial resistance (AMR) poses an increasing threat to patient care and population health and there is a growing need for novel therapies to tackle AMR. Bacteriophage (phage) therapy is a re-emerging antimicrobial strategy with the potential to transform how bacterial infections are treated in patients and populations. Currently, in the UK, phages can be used as unlicensed medicinal products on a ‘named-patient’ basis. We make an ethical case for why it is crucially important for the UK to invest in (...) Good Manufacturing Practice (GMP) for both ongoing unlicensed and future licensed phage therapy. Access to phages produced to GMP (GMP phages) will ensure effective patient care and better outcomes as well as health systems benefits. The UK also has the potential to become a global leader in the timely and cost-efficient manufacturing and supply of a therapy that meets internationally recognised standards. (shrink)

This book explains the role of simple biological model systems in the growth of molecular biology. Essentially the whole history of molecular biology is presented here, tracing the work in bacteriophages in E. coli, the role of other prokaryotic systems, and also the protozoan and algal models—Paramecium and Chlamydomonas, primarily—and the move into eukaryotes with the fungal systems Neurospora, Aspergillus and yeast. Each model was selected for its appropriateness for asking a given class of questions, and each spawned its own (...) community of investigators. Some individuals made the transition to a new model over time, and remnant communities of investigators continue to pursue questions in all these models, as the cutting edge of molecular biological research flowed onward from model to model, and onward into higher organisms and, ultimately, mouse and man. (shrink)

Artificial genetic constructs that direct the synthesis of self‐replicating RNA molecules are used widely to induce gene silencing, for bioproduction, and for vaccination. Interestingly, one variant of the self‐replicon has not been discussed in the literature: namely, transgenic organisms that synthesise alien replicons. For example, plant cells may be easily genetically modified to produce bacteriophages or insect viruses. Alien replicon‐producing organisms (ARPOs) may serve as a unique tool for biocontrol or to selectively influence the characteristics of a target organism. The (...) ARPO approach would have to meet strict biosafety criteria, and its practical applications are problematic. However, a discussion on ARPO applicability would be valuable to outline the full set of options available in the bioengineering toolbox. In this paper, RNA replicons for bioengineering are reviewed briefly, and the ARPO approach is discussed. (shrink)

The identification of proteins that interact with proliferating cell nuclear antigen (PCNA) has recently been a rapidly expanding field of discovery. PCNA is involved in many aspects of DNA replication and processing, forming a sliding platform that can mediate the interaction of proteins with DNA. It is striking that many proteins bind to PCNA through a small region containing a conserved motif; these include proteins involved in cell cycle regulation as well as those involved in DNA processing. Sequential and regulated (...) binding of motif-containing proteins to PCNA may contribute to the ordering of events during DNA replication and repair. Results from bacteriophages and archaea show that the structural basis for the interaction of this motif with PCNA is extremely ancient. The analysis of how such functional motifs have been recruited to proteins in present day organisms helps us to understand how these complex systems arose from ancestral organisms. BioEssays 22:997–1006, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

CRISPR, a recently developed gene-editing tool, has become synonymous with rapid biological advancement. While gene editing had been performed in life sciences research for decades, genetic engineering with CRISPR is much more straightforward, faster, and less expensive—and thus, the technology has been rapidly democratized. CRISPR was built on a natural mechanism, the method by which bacteria resist infections from viruses called bacteriophage. Once infected, bacteria may recognize specific genetic sequences of the invading bacteriophage virus and chop its genetic (...) material into pieces. This bacterial immune response, discovered through basic research, has been exploited by scientists to develop a gene-editing tool... (shrink)

Exploration of immune systems in prokaryotes, such as restriction‐modification or CRISPR‐Cas, shows that both innate and adaptive systems possess programmed cell death (PCD) potential. The key outstanding question is how the immune systems sense and “predict” infection outcomes to “decide” whether to fight the pathogen or induce PCD. There is a striking parallel between this life‐or‐death decision faced by the cell and the decision by temperate viruses to protect or kill their hosts, epitomized by the lysis‐lysogeny switch of bacteriophage (...) Lambda. Immune systems and temperate phages sense the same molecular inputs, primarily, DNA damage, that determine whether the cell lives or dies. Because temperate (pro)phages are themselves components of prokaryotic genomes, their shared “interests” with the hosts result in coregulation of the lysis‐lysogeny switch and immune systems that jointly provide the cell with the decision machinery to probe and predict infection outcomes, answering the life‐or‐death question. (shrink)

The recent historiography of molecular biology features key technologies, instruments and materials, which offer a different view of the field and its turning points than preceding intellectual and institutional histories. Radioisotopes, in this vein, became essential tools in postwar life science research, including molecular biology, and are here analyzed through their use in experiments on bacteriophage. Isotopes were especially well suited for studying the dynamics of chemical transformation over time, through metabolic pathways or life cycles. Scientists labeled phage with (...) phosphorus-32 in order to trace the transfer of genetic material between parent and progeny in virus reproduction. Initial studies of this type did not resolve the mechanism of generational transfer but unexpectedly gave rise to a new style of molecular radiobiology based on the inactivation of phage by the radioactive decay of incorporated phosphorus-32. These ‘suicide experiments’, a preoccupation of phage researchers in the mid-1950s, reveal how molecular biologists interacted with the traditions and practices of radiation geneticists as well as those of biochemists as they were seeking to demarcate a new field. The routine use of radiolabels to visualize nucleic acids emerged as an enduring feature of molecular biological experimentation. (shrink)

Whenever the state of a biological system is not determined solely by present conditions but depends on its past history, we can say that the system has memory. Bacteria and bacteriophage use a variety of memory mechanisms, some of which seem to convey adaptive value. A genetic type of heritable memory is the programmed inversion of specific DNA sequences, which causes switching between alternative patterns of gene expression. Heritable memory can also be based on epigenetic circuits, in which a (...) system with two possible steady states is locked in one or the other state by a positive feedback loop. Epigenetic states have been observed in a variety of cellular processes, and are maintained by diverse mechanisms. Some of these involve alternative DNA methylation patterns that are stably transmitted to daughter molecules and can affect DNA–protein interactions (e.g., gene transcription). Other mechanisms exploit autocatalytic loops whereby proteins establish the proper conditions for their continued synthesis. Template polymers other than nucleic acids (e.g., components of the cell wall) may also propagate epigenetic states. Non‐heritable memory is exemplified by parasitic organisms that bear a signature of their previous host, such as host‐controlled modification of phage DNA or porin hitchhiking in predatory bacteria. The heterogeneous nature of the examples known may be indicative of widespread occurrence of memory mechanisms in bacteria and phage. However, the actual extent, variety and potential selective value of prokaryotic memory devices remain open questions, still to be addressed experimentally. BioEssays 24:512–518, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA‐directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site‐specific transcriptional repression or (...) activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. (shrink)

During the 1940s and 1950s, the Australian microbiologist F. Macfarlane Burnet sought a biologically plausible explanation of antibody production. In this essay, we seek to recover the conceptual pathways that Burnet followed in his immunological theorizing. In so doing, we emphasize the influence of speculations on individuality, especially those of philosopher Alfred North Whitehead; the impact of cybernetics and information theory; and the contributions of clinical research into autoimmune disease that took place in Melbourne. We point to the influence of (...) local experimental and intellectual currents on Burnet’s work. Accordingly, this essay describes an arc distinct from most other tracings of Burnet’s conceptual development, which focus on his early bacteriophage research, his fascination with the work of Julian Huxley and other biologists in the 1920s, and his interest in North Atlantic experimental investigations in the life sciences. No doubt these too were potent influences, but they seem insufficient to explain, for example, Burnet’s sudden enthusiasm in the 1940s for immunological definitions of self and not-self. We want to demonstrate here how Burnet’s deep involvement in philosophical biology – along with attention to local clinical research – provided him with additional theoretic tools and conceptual equipment, with which to explain immune function. (shrink)

The generation of panels of mutant mice by homologous recombination has greatly increased the ability to assess the function of particular gene products in vivo. The ability to control the developmental stage, the tissue and the nature of the mutation would be an important innovation. A recent report(1) demonstrates that the conservative site‐specific recombination of bacteriophage P1, namely Cre‐lox, can be used successfuly in combination with homologous recombination to generate temporal‐and cell‐restricted mutations in vivo. The technical advance allows a (...) greater flexibility in gene targeting and will have a significant impact on how complex gene functions are studied in vivo. (shrink)

For many years, there has been a gap in our capacity to study the structure and organization of chromosomal DNA molecules. The very small genomes of some viruses and bacteriophages (≤ 50,000 bp or 50 kb) are amenable to analysis by conventional gel electrophoresis, while the extremely large DNA molecules (> 100,000 kb) comprising the chromosomes of higher eukaryotes have been analysed under the light microscope, using a range of banding and in situ hybridization techniques. However, intact DNA molecules with (...) sizes between these two extremes have been largely inaccessible experimentally. This gap has recently been bridged with the development of two‐dimensional electrophoretic procedures that allow the separation and purification of chromosome‐sized DNA molecules ranging from ∼ 50 kb to several thousand kb.1–3 There are currently two variations of the technique in use: pulsed field gradient (PFG) gel electrophoresis1,2 and orthogonal‐field‐alteration gel electrophoresis (OFAGE).3 Both are based on a common principle, differing primarily in the geometry of the electrodes. Already, they have been employed to determine the approximate chromosome sizes and numbers for a variety of lower eukaryotes, including yeast and several protozoa.2–10 These ‘molecular karyotypes’ provide fundamental information about the genomic organization of each organism, and allow very rapid construction of linkage maps. Surprisingly, they have also revealed a remarkable plasticity in the genomes of several lower eukaryotes. (shrink)

DNA methylation constitutes one of the pillars of epigenetics, relying on covalent bonds for addition and/or removal of chemically distinct marks within the major groove of the double helix. DNA methyltransferases, enzymes which introduce methyl marks, initially evolved in prokaryotes as components of restriction‐modification systems protecting host genomes from bacteriophages and other invading foreign DNA. In early eukaryotic evolution, DNA methyltransferases were horizontally transferred from bacteria into eukaryotes several times and independently co‐opted into epigenetic regulatory systems, primarily via establishing connections (...) with the chromatin environment. While C5‐methylcytosine is the cornerstone of plant and animal epigenetics and has been investigated in much detail, the epigenetic role of other methylated bases is less clear. The recent addition of N4‐methylcytosine of bacterial origin as a metazoan DNA modification highlights the prerequisites for foreign gene co‐option into the host regulatory networks, and challenges the existing paradigms concerning the origin and evolution of eukaryotic regulatory systems. (shrink)

RNA processing in Escherichia coli and some of its phages is reviewed here, with primary emphasis on rRNA and tRNA processing. Three enzymes, RNase III, RNase E and RNase P are responsible for most of the primary endonucleolytic RNA processing events. The first two are proteins, while RNase P is a ribozyme. These three enzymes have unique functions and in their absence, the cleavage events they catalyze are not performed. On the other hand a relatively large number of exonucleases participate (...) in the trimming of the 3′ ends of tRNA precursor molecules and they can substitute for each other. Primary processing is the first event that happens to the nascent RNA molecule, while in secondary RNA processing, the substrate is a product of a primary processing event. Although most RNA processing occurs in RNP particles, it seems that only in secondary RNA processing is the RNP particle required for the reaction. Bacteria and especially bacteriophages contain self‐splicing introns which in cases were probably acquired from other species. (shrink)

With the assumption of inactivation of small traits in bacteriophages “chromosomes” by ultraviolet irradiation the probability of multiplicity reactivation of irradiated phages is calculated. The result appears to be in agreement with the experimental results ofDulbecco.In the mathematical treatment of the problem a distinction is made between ordinary genes, with probability of inactivation negligible relative to the probability of inactivation of the whole phage, and a few vulnerable centers or genes whose probability of inactivation is not negligible. The hypothesis of (...) the existence of vulnerable centers appears necessary in order to explainDulbecco's experimental results.Postulant que de petites sections des „chromosomes” du bactériophage sont inactivés par l'irradiation ultraviolette, on a calculé la probabilité de réactivation par infection multiple des bactériophages traités par les rayons ultraviolets. Les résultats obtenus s'accordent avec les résultats expérimentaux de M.Dulbecco.Dans la tractation mathématique des problèmes une distinction a été faite entre les gènes ordinaires — dont la probabilité d'inactivation prise individuellement peut Être négligée relativement à la probabilité d'inactivation du phage entier — et quelques centres vulnérables ou gènes dont la probabilité d'inactivation ne pourrait Être négligée.L'hypothèse de l'existance des centres vulnérables s'est démontrée nécessaire à l'explication des résultats expérimentaux de M.Dulbecco.Die Wahrscheinlichkeit der Reaktivation durch multiplen Infektionen ist unter Voraussetzung, dass die Ultraviolett-Bestrahlung kleine Teile der Bakteriophagenchromosomen inaktiviert, berechnet. Das Ergebnis entspricht den experimentellen ResultatenDulbecco's.In der mathematischen Behandlung des Problems ist ein Unterschied gemacht worden zwischen gewöhnlichen Genen — wovon jeder eine geringe Wahrscheinlichkeit der Inaktivierung hat, in Bezug auf die Wahrscheinlichkeit der Inaktivierung der ganzen Bakteriophage — und einige verletzbare Stellen oder Genen, wovon die Wahrscheinlichkeit der Inaktivierung grössenordnungsmÄssig höher liegt. Die Hypothese über die verletzbaren Stellen war notwendig um die experimentellen ResultateDulbecco's zu erklÄren. (shrink)

How much bacterial evolution occurs in our intestines and which factors control it are currently burning questions. The formation of new ecotypes, some of which capable of coexisting for long periods of time, is highly likely in our guts. Horizontal gene transfer driven by temperate phages that can perform lysogeny is also widespread in mammalian intestines. Yet, the roles of mutation and especially lysogeny as key drivers of gut bacterial adaptation remain poorly understood. The mammalian gut contains hundreds of bacterial (...) species, each with many strains and ecotypes, whose abundance varies along the lifetime of a host. A continuous high input of mutations and horizontal gene transfer events mediated by temperate phages drives that diversity. Future experiments to study the interaction between mutations that cause adaptation in microbiomes and lysogenic events with different costs and benefits will be key to understand the dynamic microbiomes of mammals. Also see the video abstract here: https://youtu.be/Zjqsiyb5Pk0. (shrink)

The encounter between two fundamentally different approaches in seminal research in molecular biology-the problems, aims, methods and metaphysics - is delineated and analyzed. They are exemplified by the microbiologist Oswald T. Avery who, in line with the reductionist mechanistic metaphysics of Jacques Loeb, attempted to explain basic life phenomena through chemistry; and the theoretical physicist Max Delbrück who, influenced by Bohr’s antimechanistic views, preferred to explain these phenomena without chemistry. Avery’s and Delbrück’s most important studies took place concurrently. Thus analysis (...) of their contrasting approaches lends itself to examination of the Weltanschauungen view concerning the role of fundamental (metaphysical) assumptions in scientific change, that is, the view that empirical research cannot be neutral in regard to the worldviews of the researchers. This study shows that the initial ostensible disparity (non-integratibility) of the two approaches lasted for just a short time. Ironically it was a student of Delbrück’s school, James Watson, who (with Crick) proposed a chemical model, the DNA double helix, as a solution to Delbrück’s problem. The structure of DNA has not been seriously challenged over the past half century. Moreover, Watson’s and Crick’s work did not call into question the validity of Delbrück’s research, but opened it up to entirely new approaches. The case of Avery and Delbrück demonstrates that after initial obstacles were overcome the different fundamental attitudes and the resulting research practices were capable of integration. © 2008 Stazione Zoologica Anton Dohrn. (shrink)

In the early twentieth century, viruses had yet to be defined in a material way. Instead, they were known better by what they were not – not bacteria, not culturable, and not visible with a light microscope. As with the ill-defined “gene” of genetics, viruses were microbes whose nature had not been revealed. Some clarity arrived in 1929 when Francis O. Holmes, a scientist at the Boyce Thompson Institute for Plant Research reported that Tobacco mosaic virus could produce local necrotic (...) lesions on tobacco plants and that these lesions were in proportion to dilutions of the inoculum. Holmes’ method, the local lesion assay, provided the first evidence that viruses were discrete infectious particles, thus setting the stage for physicochemical studies of plant viruses. In a field where there are few eponymous methods or diseases, Holmes’ assay continues to be a useful tool for the study of plant viruses. TMV was a success because the local lesion assay “made the virus visible” and standardized the work of virology towards determining the nature of the virus. (shrink)