Origins Of Molecular Biology Research Articles

"Molecular Biology"-Pleonasm or Denotation for a Discipline of Its Own? Reflections on the Origins of Molecular Biology and Its Situation Today.

The disciplinary identity of molecular biology has frequently been called into question. Although the debates might sometimes have been more about creating or debunking myths, defending intellectual territory and the distribution of resources, there are interesting underlying questions about this area of biology and how it is conceptually organized. By looking at the history of molecular biology, its origins and development, I examine the possible criteria for its status as a scientific discipline. Doing so allows us to answer the title question in such a way that offers a reasonable middle ground, where molecular biology can be properly viewed as a viable interdisciplinary program that can very well be called a discipline in its own right, even if no strict boundaries can be established. In addition to this historical analysis, a couple of systematic issues from a philosophy of science perspective allow for some assessment of the current situation and the future of molecular biology.

Beadle and Tatum and the origins of molecular biology.

Recognition of the innovative nature of the Beadle and Tatum experiment of mutation induction followed by selection has faded in the decades since; Bernard Strauss explains why.

TRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

abstractThe universal genetic code is a translation table by which nucleic acid sequences can be interpreted as polypeptides with a wide range of biological functions. That information is used by aminoacyl-tRNA synthetases to translate the code. Moreover, amino acid properties dictate protein folding. We recently reported that digital correlation techniques could identify patterns in tRNA identity elements that govern recognition by synthetases. Our analysis, and the functionality of truncated synthetases that cannot recognize the tRNA anticodon, support the conclusion that the tRNA acceptor stem houses an independent code for the same 20 amino acids that likely functioned earlier in the emergence of genetics. The acceptor-stem code, related to amino acid size, is distinct from a code in the anticodon that is related to amino acid polarity. Details of the acceptor-stem code suggest that it was useful in preserving key properties of stereochemically-encoded peptides that had developed the capacity to interact catalytically with RNA. The quantitative embedding of the chemical properties of amino acids into tRNA bases has implications for the origins of molecular biology.

Chromosome replication, cell growth, division and shape: a personal perspective.

The origins of Molecular Biology and Bacterial Physiology are reviewed, from our personal standpoints, emphasizing the coupling between bacterial growth, chromosome replication and cell division, dimensions and shape. Current knowledge is discussed with historical perspective, summarizing past and present achievements and enlightening ideas for future studies. An interactive simulation program of the bacterial cell division cycle (BCD), described as “The Central Dogma in Bacteriology,” is briefly represented. The coupled process of transcription/translation of genes encoding membrane proteins and insertion into the membrane (so-called transertion) is invoked as the functional relationship between the only two unique macromolecules in the cell, DNA and peptidoglycan embodying the nucleoid and the sacculus respectively. We envision that the total amount of DNA associated with the replication terminus, so called “nucleoid complexity,” is directly related to cell size and shape through the transertion process. Accordingly, the primary signal for cell division transmitted by DNA dynamics (replication, transcription and segregation) to the peptidoglycan biosynthetic machinery is of a physico-chemical nature, e.g., stress in the plasma membrane, relieving nucleoid occlusion in the cell’s center hence enabling the divisome to assemble and function between segregated daughter nucleoids.

Looking for quantum in life

The 1935 paper ‘‘On the Nature of Gene Mutation and Gene Structure’’ by Drosophila geneticist Nikolai Timofeeff-Ressovsky, radiation physicist Karl Gunter Zimmer, and theoretical physicist Max Delbruck (a student of the physicist Niels Bohr) has held an important place in the historiography of molecular biology. Commonly known as the ‘‘Three-Man Paper,’’ it has been situated at the center of the ‘‘origins’’ narrative in the history of molecular biology. In Phage and the Origins of Molecular Biology, the 1966 festschrift for one of the authors of the Three-Man Paper, Delbruck, some of his colleagues and disciples trace the birth of molecular biology to his attempt to discover ‘‘other laws of physics’’ through his study the phenomena of life and heredity: first he used biophysical methods, such as irradiation and quantum mechanics, to understand the stability of the gene; then he studied the phage, the hydrogen atom of biology, to ask fundamental questions about the nature of heredity. According to Erwin Schrodinger, his theoretical musings in What is Life? were inspired by the ThreeMan Paper, and his somewhat mythologized version of the Three-Man Paper in turn encouraged some physicists to shift their research on the problem of genetics. Indeed, self-proclaimed molecular biologists cherished the Three-Man Paper, suggesting that it exhibits some of the salient features of their discipline: its interdisciplinary approach to the problem of heredity, especially the applications of concepts of physics and of physical instruments; and its pursuit of a reductionist understanding of life based on the action of material genes. At long last, with the publication of Creating a Physical Biology: The Three-Man Paper and Early Molecular Biology, some of the key historical and philosophical issues underlying the Three-Man Paper have been eloquently told with a scholarly attention to analytic precision. First of all, the book offers the first English translation of the Three-Man Paper. Lucidly translated by Brandon Fogel, the Three-Man Paper has been often invoked for its historical and philosophical

The Paradox of the Phage Group: Essay Review

The 1966 festschrift for Max Delbriick, Phage and the Origins of Molecular Biology, effectively launched the history of molecular biol ogy, and it still echoes resoundingly in the historiography. Just three years after its appearance Delbriick shared the Nobel Prize in Physi ology or Medicine with Alfred Hershey and Salvador Luria "for their discoveries concerning 'the replication mechanism and the genetic structure of viruses.'"1 This volume of admiring essays was no doubt among the testimonials considered by the Caroline Institute of Medicine and its Nobel Committee.2 Gunther Stent's introduction to the collec tion, "Waiting for the Paradox," best articulates the book's underlying argument that the birth of molecular biology can be traced to Del briick's decision to study bacteriophage. As the standard view goes (in Stent's telling), physicists, disenchanted over the uses of the secrets of the atom for mass destruction, read Schrodinger's What is Life? as a vocational call to discover the secret of life.3 First among this band of physical scientists who would renovate biology was Delbriick, who had

Fungal physiology and the origins of molecular biology

Molecular biology has several distinct origins, but especially important are those contributed by fungal and yeast physiology, biochemistry and genetics. From the first gene action studies that became the basis of our understanding of the relationship between genes and proteins, through chromosome structure, mitochondrial genetics and membrane biogenesis, gene silencing and circadian clocks, studies with these organisms have yielded basic insight into these processes applicable to all eukaryotes. Examples are cited of pioneering studies with fungi that have stimulated new research in clinical medicine and agriculture; these studies include sexual interactions, cell stress responses, the cytoskeleton and pathogenesis. Studies with the yeasts and fungi have been effective in applying the techniques and insights gained from other types of experimental systems to research in fungal cell signalling, cell development and hyphal morphogenesis.

Reflections on the Origin, Meaning, and Future of Systems Biology

The term molecular biology is so familiar nowadays that nobody questions its meaning. However, there was no consensus in the beginning about that, and even some people disputed that such a term corresponded to a new science. For instance, Kendrew wrote in a paper on the origin of molecular biology [4] that: “Biochemists point out that molecular biology is their own field, in a strict sense of the words, and sometimes deride the assumption of the phrase as a title by a group whose members were ignorant of biochemistry and indeed often hostile to it. . . One distinguished biochemist has referred to molecular biology as the practice of biochemistry without license.” On the other hand, molecular biologists themselves were by no means unanimous about the nature of their subject. According to Astbury [1], who introduced one of the first definitions, “molecular biology is concerned particularly with the forms of biological molecules and with the evolution, exploitation and ramification of these forms in the ascent to higher and higher levels of organization. Molecular biology is predominantly three-dimensional and structural — which does not mean, however, that it is merely a refinement of morphology. It must at the same time inquire into genesis and function.” Interestingly, this definition does not even mention biological information or genetics. However, by the time the term molecular biology had become popular, in the 1950’s, and many research institutes and university departments had been organized under that name, its meaning had evidently widened to include also molecular genetics [9]. And, as Kendrew points out [4], though molecular geneticists were interested in such matters as the DNA double helix, “the features of that structure that had been important to them had not been geometrical so much as topological:

Present at the flood: How structural biology came about, by Richard E. Dickerson

<i>Present at the flood: How structural biology came about,</i> by Richard E. Dickerson

Physics and the origins of molecular biology

Bohr, Delbrück and Schrödinger were physicists who had important influences on biology in the second half of the twentieth century. They thought that future studies of the gene might reveal new principles or paradoxes, analogous to the wave/particle paradox of light propagation, or even new physical laws. This stimulated several physicists to enter the field of biology. Delbrück founded the bacteriophage group which provided one of the roots of molecular biology. Another was X-ray crystallography which led to the discovery of DNA structure. The strength and success of molecular biology came from the many interactions between geneticists, physicists, chemists and biochemists. It was also characterized by a powerful combination of theoretical and experimental approaches.

The favorable features of tryptophan synthase for proving Beadle and Tatum's one gene-one enzyme hypothesis.

LAST year we celebrated the 100th anniversary of the birth of George Beadle. He, with Edward Tatum, in 1941, proposed one of the major conceptual advances in biology in the 20th century: the existence of a one gene–one enzyme relationship (Beadle and Tatum 1941).2 Unfortunately, like many biologists proposing exciting hypotheses, they could not provide the experimental evidence that would prove they were correct. At that time, the existing knowledge about gene and enzyme structure was inadequate to permit the relationship's verification. George Beadle was aware of this and undoubtedly regretted his inability to provide support for their hypothesis. In a retrospective article written for Phage and the Origins of Molecular Biology, Beadle (1966)(p. 30) states that at the Cold Spring Harbor Symposium of 1951 “the number whose faith in one gene–one enzyme remained steadfast could be counted on the fingers of one hand—with a couple of fingers left over.” Why? Why was their proposed basic relationship not accepted? Why could they not provide proof for their hypothesis? Beadle and Tatum's principal difficulty was that in the 1940s we knew relatively little about the chemical nature of genetic material. The prevailing view then was that genetic material might be protein. Existing information on DNA structure suggested that it consisted of repetitive nucleotide sequences. If correct, it would be unlikely that DNA could specify the many different proteins present in each organism. Also, it was not yet firmly established that polypeptides consist of linear sequences of amino acids. Therefore, during the early years following Beadle and Tatum's proposal of the one gene–one enzyme relationship, our understanding of the structural features of genes and enzymes was insufficient to allow formulation of a finite molecular relationship. Advances in the 1950s dealt with most of these issues and suggested a plausible experimental strategy that could be applied in comparing the structural features of a gene with that of its corresponding protein. One of the earliest relevant findings, by Avery et al. (1944), suggested that the pneumococcal transforming principle—presumably the genetic material of the organism—was very likely DNA (see Lederberg 1994). Unfortunately, the significance of this finding was not appreciated initially; questions were raised about the purity of the transforming principle, our understanding of the transformation process was incomplete, and doubts existed that pneumococcal genetic material would be structurally comparable to the genetic material of higher organisms. Somewhat later, in the early 1950s, Al Hershey and Martha Chase presented their isotopic labeling studies with bacteriophage-infected Escherichia coli. Their results provided what was considered convincing evidence that phage genetic material is in fact DNA (Hershey and Chase 1952; see Stahl 1998). Most importantly, in 1953, Jim Watson and Francis Crick described the double-helical structure of DNA (Watson and Crick 1953). Their contribution changed forever how genetic material would be viewed by everyone. The realization that each gene probably consists of a linear sequence of nucleotides prompted subsequent thought on the existence of a genetic code, an essential consideration with a direct bearing on the gene-enzyme relationship. During this period Matt Meselson and Frank Stahl established that DNA is replicated by synthesis of complementary DNA strands, revealing the elegant features of DNA structure that provide for its exact replication (Meselson and Stahl 1958). Also of great importance, Fred Sanger showed that an insulin polypeptide consists of a unique linear sequence of amino acids (Sanger 1952; Stretton 2002). The significance of the contributions of Sanger, Erwin Chargaff, and others are described in an article by Horace Judson (Judson 1993). The discoveries cited, and observations by others supporting their conclusions, redefined the gene–enzyme relationship of Beadle and Tatum as the gene-protein colinearity hypothesis. Despite these advances in the 1950s, the technology that would have allowed either isolation of a gene or determination of its nucleotide sequence was lacking. Furthermore, since the concept of the genetic code was yet to be developed, knowledge of Watson and Crick's double-helical structure of DNA was initially of little help to those wishing to experimentally address the structural relationship between a gene and the enzyme it was proposed to specify. In the late 1950s Seymour Benzer demonstrated that one could construct a linear fine-structure genetic map by crossing mutants with genetically separable alterations in the same genetic region (Benzer 1957). His findings were consistent with the interpretation that a gene consists of a specific linear sequence of nucleotides. At approximately the same time, Vernon Ingram identified the amino acid change in the hemoglobin of humans with sickle cell anemia, and he developed the protein “fingerprinting” technique, a method that could be applied in detecting the single amino acid change in any mutant protein (Ingram 1958; see Ingram 2004). These two advances provided an excellent pair of experimental approaches that could be applied immediately in testing the gene–protein colinearity concept.

The origins of molecular biology: A Pedagogical tool for the professional development of pre‐college science teachers

AbstractWe examine the science and pedagogy behind a historical approach to the professional development of pre‐college science (primarily biology) teachers. Our intention is to reach professional scientists, who, as a group, are uniquely qualified to provide experience and insights essential to this approach. The underlying research for this article has been carried out during an 8‐week summer course for selected rural high school science teachers at the Oklahoma Medical Research Foundation in Oklahoma City, Oklahoma. Now configured as part of the broader Oklahoma Science Project, the Summer Course has been held during each of the past 10 years. The result of our experiences is a learning model that incorporates a research dynamic based on peer interactions and Robert K. Merton's concept of specified ignorance. This dynamic is organized around carefully chosen research topics based on simple, quantitative assays that played important roles in the development of our current understanding of genetic chemistry. These assays are starting points for rationally conceived research projects developed by the teachers themselves. We illustrate this approach with the plaque assay for bacterial viruses.

Félix d’Herelle and the Origins of Molecular Biology, by William C. Summers

<i>Félix d’Herelle and the Origins of Molecular Biology,</i> by William C. Summers

Erwin Schrödinger and the origins of molecular biology.

ERWIN Schrodinger (1887–1961) was a distinguished physicist who won the Nobel prize in 1933 for his pioneering work on wave mechanics. Yet, to biologists his name is permanently connected with a little book, entitled What Is Life? , that was greatly influential in inspiring a number of pioneers

History of phage research as viewed by a European

The history of phage research as the origin of molecular biology is related as seen by a scientist located at that critical time in Geneva. The preponderant influence of Max Delbrück on these developments is traced as a consequence of his personal charisma. Jean Weigle, former professor of experimental physics in Geneva and later research fellow with Delbrück, acted as an important ambassador to the European groups.

History of phage research as viewed by a European

The history of phage research as the origin of molecular biology is related as seen by a scientist located at that critical time in Geneva. The preponderant influence of Max Delbruck on these developments is traced as a consequence of his personal charisma. Jean Weigle, former professor of experimental physics in Geneva and later research fellow with Delbruck, acted as an important ambassador to the European groups.

Max Perutz's achievements: how did he do it?

Protein ScienceVolume 3, Issue 10 p. 1625-1628 Invited TributeFree Access Max Perutz's achievements: How did he do it? David Eisenberg, Corresponding Author David Eisenberg [email protected] UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute, and Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90024–1570UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute, and Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90024–1570Search for more papers by this author David Eisenberg, Corresponding Author David Eisenberg [email protected] UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute, and Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90024–1570UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute, and Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90024–1570Search for more papers by this author First published: October 1994 https://doi.org/10.1002/pro.5560031001Citations: 14AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Bragg WL, Perutz MF. 1954. The structure of haemoglobin: Fourier projections on the 010 plane. Proc R Soc Lond Ser A 225: 315– 329. Fermi G, Perutz MF, Shaanan B, Fourme R. 1984. The crystal structure of human deoxyhaemoglobin at 1.74 Å resolution. J Mol Biol 175: 159– 174. Haurowitz F. 1938. Das Gleichgewicht zwischen Hämoglobin und Sauerstoff. Hoppe-Seyler 254: 266– 274. Judson HF. 1979. The eighth day of creation: Makers of the revolution in biology. New York: Simon & Schuster. Kendrew JC, Dickerson RE, Strandberg BE, Hart RG, Davies DR, Phillips DC, Shore VC. 1960. Structure of myoglobin: A three-dimensional Fourier synthesis at 2 Å resolution. Nature 185: 422– 427. Perutz MF. 1970. Stereochemistry of cooperative effects in hemoglobin. Nature 373: 726– 739. Perutz MF. 1980. Origins of molecular biology. New Scientist 85 (1192): 326– 329. Perutz M. 1984. Review of Rutherford by David Wilson. London Review of Books 6 (7): 7– 8. [Also reprinted in Is Science Necessary?] Perutz M. 1985a. Early days of protein crystallography. Methods Enzymol 114: 3– 19. Perutz M. 1985b. That was the war: Enemy alien. The New Yorker Aug. 12 1985. pp 35– 54. [Also reprinted in Is Science Necessary?] Perutz M. 1989. Is science necessary? New York: E.P. Dutton. Perutz M, Johnson T, Suzuki M, Finch JT. 1994. Glutamine repeats as polar zippers: Their possible role in inherited neurodegenerative disease. Proc Natl Acad Sci USA 91: 5355– 5358. Perutz MF, Muirhead H, Cox JM, Goaman LC. 1968. Three-dimensional fourier synthesis of horse oxyhemoglobin at 2.8 Å resolution: The atomic model. Nature 219: 131– 139. Perutz MF, Rossmann MG, Cullis AF, Muirhead H, Will G, North ACT. 1960. Structure of haemoglobin: A three-dimensional Fourier synthesis at 5.5 Å resolution, obtained by X-ray analysis. Nature 185: 416– 422. Rossmann MG. 1960. The accurate determination of the position and shape of heavy-atom replacement groups in proteins. Acta Crystallogr 13: 221– 226. Citing Literature Volume3, Issue10October 1994Pages 1625-1628 ReferencesRelatedInformation

The Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the New Biology by Lily E. Kay

TECHNOLOGYAND CULTURE Book Reviews 883 embedded in both federal science policy and legal interpretation as a crucial incentive to innovation. SheilaJasanoff’s study of risk assessment at the Environmental Protection Agency—what she too efifacingly calls “a modest exemplar of the way to study ‘science after ’40’ ”—demon­ strates how much political scientists can teach us about interpreting the regulatory structure so central in the postwar state. As those of us working in the field know all too well, the documentary sources for the history of recent science present some unique chal­ lenges. Beyond the more or less straightforward problems of classified and proprietary material, electronic technologies that do not leave paper trails, and the massive quantities of material, there are more subtle issues about how our sources may be shaping our histories. In a thoughtful analysis of the cold fusion episode, Bruce Lewenstein shows how media coverage “framed” its meaning for the public and the scientific community alike, in ways that future historians will have to consider. Joan Wamow-Blewett surveys the efforts to preserve the record of recent science and technology and provides an invaluable guide to disciplinary history centers, archival projects, and publications. As might be expected, corporations and government agencies are saving the records and funding the research. Reading through the list with Lewenstein’s critique in mind raises some troubling questions about the sources of our sources and how they may be framing the meaning of recent science in ways we have not even really begun to consider. Stuart W. Leslie Dr. Leslie teaches the history ofscience and technology atJohns Hopkins University and recendy published The Cold War and American Science: The Military-Industrial-Academic Complex at MIT and Stanford. The Molecular Vision ofLife: Caltech, the RockefellerFoundation, and the Rise of the New Biology. By Lily E. Kay. NewYork: Oxford University Press, 1993. Pp. x+304; illustrations, notes, index. $49.95. It can reasonably be claimed that molecular biology is one of the defining sciences of the late 20th century. Not only is it an intellectual enterprise with remarkable scholarly fruits, it is also widely seen to underpin biotechnology in a manner that seemingly exemplifies the relationships between science and high technology. The early histories such as the 1966 Festschrift for Max Delbruck, Phage and the Origins of MolecularBiology, portrayed a straightforward historical progression seen through the lens of one key school. As professional historians took over, however, developments seemed to become more complex. Even the phrase “molecular biology” proved to have been problematic: its most significant early use in the 1930s was by Warren Weaver, not an intellectual giant but an officer of the Rockefeller Foundation. His work has attracted studies of the foundation’s proactive strategies, which have 884 Book Reviews TECHNOLOGYAND CULTURE proved to be among the liveliest and most dynamic aspects of the history of science as a whole. Major contributors have included Pnina Abir-Am and Robert Kohler in their studies focused on molecular biology and the Rockefeller, respectively. In a series of papers and in his recent book Partners in Science, Kohler showed the complex factors underlying the motivations of foundation officers such as Warren Weaver and their clients, including such luminaries as Linus Pauling. From the work of Abir-Am, we are now aware that there were many institutional traditions underpinning modern molecular biology. Cambridge, England, is one site that is attracting much attention; Paris’s Pasteur Institute, home of Jacob and Monod, was also crucial. Many other key developments, whether associated with Morgan, Beadle, or Delbruck, took place at Caltech, whose own history has in its turn been recounted by Judith Goodstein. Now Lily Kay has brought together much of the existing work to give us a coherent account ofthe evolution ofmolecular biology in Pasadena. Although this work would not have been lessened by a greater acknowledgment of the contribution ofothers, it does go beyond existing literature in the strength of its claims about the way in which goals of social control in the vision of key players—as patrons in the Pasadena area, sponsors at the Rockefeller, and researchers at the university— underpinned the endeavor of molecular biology. In the era of the seamless web, complex...

The early days of yeast genetics

In a series of illustrated scientific reminiscences much along the lines of Phage and the Origins of Molecular Biology, the history of yeast genetics is recorded as viewed by the protagonists themselves, who describe how specific topics or lines of investigation in which they were involved develope

OVATOOMB: other viruses and the origins of molecular biology.

Evolution de l'interet porte aux virus depuis le debut du 20eme siecle, a savoir depuis la decouverte des maladies infectieuses tant des plantes que des animaux jusqu'a l'utilisation des virus en tant que materiel de recherche en biologie moleculaire