Landmark Experiments in Molecular Biology - 1st Edition - ISBN: 9780128020746, 9780128021088

Landmark Experiments in Molecular Biology

1st Edition

Authors: Michael Fry
eBook ISBN: 9780128021088
Paperback ISBN: 9780128020746
Imprint: Academic Press
Published Date: 6th July 2016
Page Count: 570
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Landmark Experiments in Molecular Biology critically considers breakthrough experiments that have constituted major turning points in the birth and evolution of molecular biology. These experiments laid the foundations to molecular biology by uncovering the major players in the machinery of inheritance and biological information handling such as DNA, RNA, ribosomes, and proteins. Landmark Experiments in Molecular Biology combines an historical survey of the development of ideas, theories, and profiles of leading scientists with detailed scientific and technical analysis.

Key Features

  • Includes detailed analysis of classically designed and executed experiments
  • Incorporates technical and scientific analysis along with historical background for a robust understanding of molecular biology discoveries
  • Provides critical analysis of the history of molecular biology to inform the future of scientific discovery
  • Examines the machinery of inheritance and biological information handling


Researchers and graduate students in molecular biology, biochemistry, and cell biology, and those researching the history of science.

Table of Contents

  • Dedication
  • About the Author
  • Preface
  • Chapter 1. Introduction: Origins, Brief History, and Present Status of Molecular Biology
    • Abstract
    • 1.1 Origins and Early Uses of the Term “Molecular Biology”
    • 1.2 What Is Molecular Biology?
    • 1.3 Further Reading
    • References
  • Chapter 2. Prehistory of Molecular Biology: 1848–1944: The Discoveries of Chromosomes and of Nucleic Acids and Their Chemistry
    • Abstract
    • 2.1 Discovery of the Cell Nucleus and Protoplasm and the Formulation of the Cell Theory
    • 2.2 Chromatin, Chromosomes, and Mitosis Discovered
    • 2.3 The Hoppe-Seyler School of Physiological Chemistry: Incubator to the Discovery of Nucleic Acids
    • 2.4 Unraveling the Chemistry of Nucleic Acids—The Work of Phoebus Levene
    • References
  • Chapter 3. Avery, MacLeod, and McCarty Identified DNA as the Genetic Material: A Celebrated Case of a Clinical Observation That Led to a Fundamental Basic Discovery
    • Abstract
    • 3.1 Pneumonia–“The Captain of the Men of Death”
    • 3.2 From a Clinical Observation to the Discovery of Bacterial Transformation: The Work of Frederick Griffith
    • 3.3 Transformation Was Promptly Confirmed
    • 3.4 Establishment of an In Vitro Transformation System Offered a First Glimpse of the Transforming Principle
    • 3.5 The Latent Period: No Published Results Between Alloway’s 1933 Report and the 1944 Announcement That the Transforming Principle Was DNA
    • 3.6 Enters McCarty: Critical Experiments Identified the Transforming Principle as DNA
    • 3.7 1944: DNA Was Formally Proclaimed to be the Transforming Material
    • 3.8 The Avery, MacLeod, and McCarty Landmark 1944 Paper
    • 3.9 Reception of the Avery, MacLeod, and McCarty Paper
    • 3.10 Multiple Factors Contributed to the Belated Recognition of the Significance of the Discovery of Avery, MacLeod, and McCarty
    • 3.11 The Scientific Establishment Was Ambivalent About the Importance of Avery’s discovery
    • 3.12 After 1944: Additional Experiments Strengthened the Case for DNA as the Transforming Agent
    • 3.13 Epilogue: Avery’s Legacy
    • References
  • Chapter 4. Hershey and Chase Clinched the Role of DNA as the Genetic Material: Phage Studies Propelled the Birth of Molecular Biology
    • Abstract
    • 4.1 The Latent Period 1944–52: Although DNA Was Identified as the Pneumococcal-Transforming Factor It Was Not Universally Recognized as the Genetic Material
    • 4.2 The Discovery of Bacterial Viruses
    • 4.3 Introduction of Bacteriophage as Model System
    • 4.4 Luria and Anderson Had a First Glimpse of Bacteria-Infecting Phage
    • 4.5 The Luria–Delbrück Experiment
    • 4.6 DNA Was Assigned Only a Secondary Role in Early Thinking on the Chemical Nature of Phage Genetic Material
    • 4.7 Despite His Active Studies on Phage Genetics, Hershey Showed at First Only Tacit Interest in the Chemical Nature of the Genetic Material
    • 4.8 First Step Toward the Identification of DNA as the Genetic Material of Phages: Virus Killing by Radioactive Phosphorous Implied a Vital Role for Nucleic Acids
    • 4.9 Laying the Groundwork for the Hershey and Chase Experiment: Phage DNA and Protein Were Shown to be Separable
    • 4.10 The Hershey and Chase Experiment Identified DNA as the Genetic Material of Phage
    • 4.11 Early Reaction to the Hershey and Chase Results
    • 4.12 The Contributions of Avery, MacLeod, and McCarty, of Hershey and Chase, and of Watson and Crick to the Identification of DNA as the Genetic Material
    • 4.13 Epilogue: Hershey’s Peculiar Late Version of the Source of His Experiment With Chase
    • References
  • Chapter 5. Discovery of the Structure of DNA: The Most Famous Discovery of 20th Century Biology
    • Abstract
    • 5.1 Early History of X-Ray Crystallography
    • 5.2 The Emergence of X-Ray Crystallography of Biological Molecules
    • 5.3 Early Studies of Diffraction of X-Rays by DNA Fibers
    • 5.4 Erwin Chargaff’s Discovery of Base Complementarity in DNA
    • 5.5 Studies at King’s College on the Diffraction of X-Rays in DNA Fibers
    • 5.6 First Models of DNA Were Built by Watson and Crick and by Linus Pauling
    • 5.7 Reception of the Double Helix Model of DNA
    • 5.8 After the Discovery
    • References
  • Chapter 6. Meselson and Stahl Proved That DNA Is Replicated in a Semiconservative Fashion: An Elegant Experiment Decided Among Three Competing Theoretical Models of the Mechanics of DNA Replication
    • Abstract
    • 6.1 Theoretical Considerations Bred Three Competing Abstract Models of DNA Replication
    • 6.2 Early Experimental Testing of the Alternative Theoretical Models of Replication
    • 6.3 Herbert Taylor’s Examination of Duplicating Chromosomes Was Consistent With a Semiconservative Mode of Replication
    • 6.4 A Critical Experiment by Meselson and Stahl Provided a Practically Unequivocal Corroboration of the Semiconservative Model of Replication
    • 6.5 Alternative Interpretations of the Meselson and Stahl Results Were Refuted
    • 6.6 Postscript: The Distinctive Status of the Meselson and Stahl Experiment
    • References
  • Chapter 7. Defining the Genetic Code: Evolving Ideas on the Nature of the Genetic Code and the Unraveling of Its General Attributes
    • Abstract
    • 7.1 Roles of Theory and Experiment in the Definition of the Genetic Code
    • 7.2 Challenges of the Coding Problem
    • 7.3 Roots of the Idea of Biological Information Transfer and of a Genetic Code
    • 7.4 RNA Assumed Center Stage
    • 7.5 Theory Predicted a Commaless Triplet-Based But Nondegenerate Code
    • 7.6 Experimental Results Proved the Code to Be Nonoverlapping
    • 7.7 The Code Was Experimentally Proven to Be a Sequence of Contiguous Triplet Codons
    • 7.8 Postscript: Place and Merit of Theory and Experiment in the Elucidation of the Nature of the Genetic Code
    • References
  • Chapter 8. The Adaptor Hypothesis and the Discovery of Transfer RNA: Crick’s Prescient Hypothesis of an Adaptor Molecule and the Independent Identification by Zamecnik and Hoagland of Transfer RNA and Activating Enzymes
    • Abstract
    • 8.1 The Early Days: Polymerization of Amino Acids Into Protein Was Believed to Be Catalyzed by Synthetic Reverse Action of Proteolytic Enzymes
    • 8.2 Construction and Characterization of a Cell-Free Protein Synthesis System
    • 8.3 In the Meantime in Cambridge … Crick Presciently Envisaged an Adaptor Molecule
    • 8.4 Back in Boston … Discovery of Amino Acid–Activating Enzymes and of the Actual RNA Adaptors
    • 8.5 The Coding Properties of tRNA Were Shown to Determine the Identity of Incorporated Amino Acids
    • 8.6 Postscript: Back to Crick’s Visionary View of the Adaptor as an Essential Nexus in the Flow of Genetic Information
    • References
  • Chapter 9. The Discovery and Rediscovery of Prokaryotic Messenger RNA: Initial Detection of Messenger RNA Was Overlooked Until It Was Discovered Again
    • Abstract
    • 9.1 Early Experiments With Giant Acetabularia Cells Demonstrated That Nucleus-Dictated Genetic Information Was Transmitted to and Expressed in the Cytoplasm
    • 9.2 RNA Was Linked to Protein Synthesis
    • 9.3 The Ribosome as Carrier of Genetic Information: Emergence of a “One Gene–One Ribosome–One Protein” Hypothesis
    • 9.4 Accumulating Experimental Evidence Contradicted the “One Gene–One RNA–One Ribosome–One Protein” Hypothesis
    • 9.5 Experiment Bred a New Theory: The PaJaMo Experiment and the Hypothesis of an Unstable Messenger
    • 9.6 A First Sighting of Rapidly Turning-Over RNA in Phage-Infected Cells
    • 9.7 Rapidly Synthesized DNA-Like RNA Was Also Identified in Yeast Cells
    • 9.8 Belief in Ribosomal RNA as the Carrier of Genetic Information Persisted In Spite of Contradictory Evidence and the Identification of DNA-Like RNA
    • 9.9 “The Penny Drops”—mRNA Replaced Ribosomal RNA as the Carrier of Genetic Information
    • 9.10 Eureka Moment: Crick Drew a Theory of mRNA While Brenner and Jacob Designed Experiments for Its Detection
    • 9.11 Brenner, Jacob, and Meselson Detected Labile RNA in Phage-Infected Cells
    • 9.12 The Harvard Group Identified a Minor Fraction of Rapidly Turning Over RNA in Uninfected Bacteria
    • 9.13 Despite the Discovery of Ribosome-Associated Labile RNA, It Still Remained to be Shown That This RNA Was the Carrier of Information From DNA
    • 9.14 Phage and Bacterial Proteins, and Implicitly Their mRNA Were Shown to be Collinear With Their DNA Genes
    • 9.15 The Demonstrated Collinearity Between Prokaryotic Gene and Protein Bred a Misleading Preconception That Collinearity Was Universal in All the Living Organisms
    • 9.16 Postscript: The Discovery of mRNA Was Driven by Experiment and Not by Theoretical Propositions
    • References
  • Chapter 10. The Deciphering of the Genetic Code: Nirenberg and Khorana Decrypt the Genetic Code
    • Abstract
    • 10.1 A Crucial First Step: Construction of Cell-Free Protein Synthesis System from Escherichia coli
    • 10.2 Marshall Nirenberg and His Supportive Scientific Environment at the NIH
    • 10.3 The Early Phase: Defined Polynucleotide Sequence Dictated Incorporation of a Specific Amino Acid Into Protein in a Cell-Free System
    • 10.4 The Second Phase: The Nirenberg Team Determined the Base Sequences of All 64 Codons
    • 10.5 Nirenberg’s Style of Doing Science and His Personal Demeanor
    • 10.6 The Independent Decryption of the Code by the Master Bioorganic Chemist Har Gobind Khorana
    • 10.7 After Breaking the Code, Khorana Undertook New Difficult Challenges
    • 10.8 Postscript: The Unsolved Questions of the Origin of the Code and of the Evolution of the Translation Machinery
    • References
  • Chapter 11. The Surprising Discovery of Split Genes and of RNA Splicing: The Discovery of Split Genes and of RNA Splicing in Eukaryotes Defeated the Preconception of the Universality of Gene–mRNA Collinearity
    • Abstract
    • 11.1 First Clue: Most of the Nuclear RNA Broke Down in the Nucleus Without Ever Reaching the Cytoplasm
    • 11.2 A Second Finding: Giant Molecules of Unstable RNA Were Detected in the Nucleus
    • 11.3 First Hints That the Labile Giant Nuclear RNA May Be Related to Messenger RNA
    • 11.4 Relationship of Polysome-Associated mRNA to hnRNA
    • 11.5 Conserved Tags at the 3′- and 5′-Ends of hnRNA and of mRNA Substantiated Their Precursor–Product Relationship
    • 11.6 Split Genes Discovered: Adenovirus mRNA Was Found to Be NonCollinear With the Transcribed Gene
    • 11.7 Postscript: Why Did Theory Fail to Predict Splicing?
    • References
  • Chapter 12. Postscript: On the Place of Theory and Experiment in Molecular Biology
    • Abstract
    • 12.1 Three Cases Illustrate That the Power of Theory Diminishes With Increased Complexity of an Investigated Problem
    • 12.2 Semiconservative DNA Replication
    • 12.3 Definition and Deciphering of the Genetic Code
    • 12.4 Identification and Detection of Prokaryotic mRNA
    • 12.5 The Complexity of Biology Constrains the Power of Theory
    • References
  • Index


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© Academic Press 2016
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About the Author

Michael Fry

Department of Biochemistry, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, POB 9649, Bat Galim, Haifa, 31096, Israel

Affiliations and Expertise

Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel


"The title of the book perfectly summarizes Michael Fry’s aim: to present in a simple educational way the most beautiful and significant experiments in the history of molecular biology. The most significant contribution of this publication is probably the beautiful and precise experimental illustrations that have been specially drawn to accompany an equally precise and complete description of the experiments described in the book. Michael Fry has also added a long list of references, to the original articles, to the comments made by the scientists involved, and to the work of historians. This book will be useful, but the historian will not be wholly happy with it. What is missing.... in the book in general, is a meta-level of interpretation not limited to that of the participants, a meta-level mixing analysis of the context, philosophical issues not limited to the too general debate on the opposition between theory and experiment, and a precise study of the dynamics of the events that led to the discovery. Maybe Michael Fry was too modest and too admiring of the work that was accomplished to do what a historian would expect: resurrect the context that even the participants have often forgotten and sometimes never clearly distinguished, to show how tortuous the pathway of discovery was, how the ideas that led to the truth were often wrong. This ‘unvarnished’ history, leaving as much space to mistakes as to successes, is the only one that can be truly useful to future scientists." -- Professor Michel Morange, History and Philosophy of the Life Sciences

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