Landmark Experiments in Molecular Biology

Michael Fry

• Publisher: Academic Press
• Year: 2016
• Print ISBN: 9780128020746
• eBook ISBN: 9780128021088
• Topic: Biological Sciences
• Subtopic: Molecular Biology
• Index: Biological Sciences

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.- 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

Chapter 1

Introduction

Origins, Brief History, and Present Status of Molecular Biology

Abstract

This introduction tracks the origins and early uses of the term “Molecular Biology”; it describes the historical division of this scientific discipline into structural and informational branches and briefly considers its principal tenets and attributes. In the last part of the chapter readers are directed to selected scholarly books and articles on facets of molecular biology that this book does not cover.

Keywords

Molecular biology; structural molecular biology; informational molecular biology; phage group; system biology; synthetic biology; Warren Weaver; Sydney Brenner

Chapter Outline

1.1 Origins and Early Uses of the Term “Molecular Biology” 1

1.2 What Is Molecular Biology? 3

1.2.1 Fundamental Tenets of Molecular Biology 3

1.2.2 Prevalence and Continued Success of Molecular Biology 4

1.3 Further Reading 5

1.3.1 General History of Molecular Biology 5

1.3.2 Monographs, Festschrifts, Autobiographies, and Biographies 6

1.3.3 Articles on Different Facets of Molecular Biology 7

References 8

Since its birth in the 1950s molecular biology has developed into a dominant and exceptionally productive branch of the life sciences. This introduction briefly traces the roots of the term “molecular biology”; it delineates its structural and informational branches and points to their principal tenets. Finally the reader is directed to selected scholarly articles on facets of molecular biology that are not covered in this book.

1.1 Origins and Early Uses of the Term “Molecular Biology”

The term “Molecular Biology” was first coined by the mathematician and science administrator Warren Weaver (1894–1978). Between 1932 and 1955 he served as director of the Division of Natural Sciences at the Rockefeller Foundation, which was the dominant funding agency of scientific research in Europe and America between the two World Wars.^1–6 Weaver recognized early on that tools and techniques of chemistry and physics could be adopted to study life at the molecular level. In this context he introduced the term “Molecular Biology” in a 1938 annual report to the Rockefeller Foundation (cited in Ref. 7, p. 442):

And gradually there is coming into being a new branch of science—molecular biology—which is beginning to uncover many secrets concerning the ultimate units of the living cell […] Among the studies to which the Foundation is giving support is a series in relatively new field, which may be called molecular biology, in which delicate modern techniques are being used to investigate ever more minute details of certain life processes.

Notably, Weaver’s proposal to employ the “delicate” modern techniques (implicitly of physics and chemistry) to study biology at “more minute” (molecular) details did not specify the domains of this new branch of science. When the term “Molecular Biology” began to take root in the 1950s, one of its earliest advocates, the British physicist and X-ray crystallographer William Astbury (1898–1961) (see Chapter 5: “Discovery of the Structure of DNA”) professed in 1951⁸ and reiterated in 1961⁹ that the objective of molecular biology was the investigation of the structure, origins, and functions of biomolecules:

[Molecular biology] implies not so much a technique as an approach, an approach from the viewpoint of the so-called basic sciences with the leading idea of searching below the large-scale manifestations of classical biology for the corresponding molecular plan. It is concerned particularly with the forms of biological molecules, and with the evolution, exploitation and ramification of those forms in the ascent to higher 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.

While the structural view of molecular biology was taking shape a burgeoning informational (genetic) school also claimed proprietorship of molecular biology.^10–13 This school was hatched by the Phage Group, a loose association of researchers who used bacterial viruses (bacteriophages) as a model system (see Chapter 4: “Hershey and Chase Clinched the Role of DNA as the Genetic Material”). Adherents of this school viewed the goal of molecular biology to be the elucidation of the molecular mechanisms of heredity. Leading figures of the Phage Group; Max Delbrück (1906–81), Salvador Luria (1912–91) and Alfred (Al) Hershey (1908–97) exploited induced mutations and genetic recombination to define the nature of genes. Despite its early division into structural and informational branches, molecular biology was and still remains to this day an inexactly defined discipline.¹⁴

1.2 What Is Molecular Biology?

The vague definition of molecular biology was nicely illustrated by the explanation that was given by Francis Crick (1916–2004) of how he became a molecular biologist¹⁵:

I myself was forced to call myself a molecular biologist because when inquiring clergymen asked me what I did, I got tired of explaining that I was a mixture of crystallographer, biophysicist, biochemist, and geneticist – an explanation which in any case they found too hard to grasp.

So what indeed is molecular biology? The historian Michel Morange defined it in its simplest form as: “[…] that part of biological research in which explanations are looked for at the level of molecules, by a description of their structure and interactions”.¹⁶ He was quick, however, to point out that the investigated “molecules” were actually macromolecules. More specifically, molecular biologists are interested in nucleic acids and proteins, whereas other macromolecules such as polysaccharides or long-chain lipids remain in the provinces of biochemistry and cell biology. Even after constraining molecular biology to nucleic acids and proteins and after it branched out into structural and genetic schools, its boundaries remained somewhat arbitrary. Thus, for instance, parts of photosynthesis that have all the attributes of molecular biology were never labeled as bona fide molecular biology.¹⁷

Evolved out of X-ray crystallography, structural molecular biology aimed at determining the atomic structure of macromolecules, their modes of action, and interaction with other molecules. Early spectacular achievements of this branch of molecular biology were the discovery in the 1950s of the double helix structure of DNA and the solution of the three-dimensional structure of the proteins myoglobin and hemoglobin (see Chapter 5: “Discovery of the Structure of DNA”). Employment in the next decades of spectroscopy, electron microscopy, nuclear magnetic resonance, and X-ray diffraction analysis solved the atomic structure of numerous DNA and RNA molecules and of more than 100,000 different proteins. The informational/genetic school of molecular biology used in its earliest phase bacteriophage and bacterial model systems. By combining genetic and mostly biochemical techniques, this school deciphered the genetic code,¹⁸ identified major elements of the protein synthesis machinery, and outlined the mechanics of gene expression.¹⁹ The development in the next decades of methods to sequence proteins and nucleic acid, the advent of recombinant DNA technologies, and the employment of diverse cellular and molecular biology approaches greatly expanded our understanding of the operation and regulation of the genetic machinery.

1.2.1 Fundamental Tenets of Molecular Biology

Because molecular biology is the product of historical circu...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• About the Author
• Preface
• Chapter 1. Introduction: Origins, Brief History, and Present Status of Molecular Biology
• Chapter 2. Prehistory of Molecular Biology: 1848–1944: The Discoveries of Chromosomes and of Nucleic Acids and Their Chemistry
• 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
• Chapter 4. Hershey and Chase Clinched the Role of DNA as the Genetic Material: Phage Studies Propelled the Birth of Molecular Biology
• Chapter 5. Discovery of the Structure of DNA: The Most Famous Discovery of 20th Century Biology
• 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
• Chapter 7. Defining the Genetic Code: Evolving Ideas on the Nature of the Genetic Code and the Unraveling of Its General Attributes
• 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
• Chapter 9. The Discovery and Rediscovery of Prokaryotic Messenger RNA: Initial Detection of Messenger RNA Was Overlooked Until It Was Discovered Again
• Chapter 10. The Deciphering of the Genetic Code: Nirenberg and Khorana Decrypt the Genetic Code
• 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
• Chapter 12. Postscript: On the Place of Theory and Experiment in Molecular Biology
• Index