Life Explained

Michel Morange

• Publisher: Odile Jacob
• Year: 2003
• Print ISBN: 9782738147493
• eBook ISBN: 9782738147516
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

"Fifty years ago, Francis Crick and James D. Watson discovered the double-helix structure of DNA, the carrier of genetic information, the basis for heredity. They believed they had, according to Francis Crick's own expression, found "the secret of life." The main aim of this book is to continue the story beyond the double helix and interpret recent developments through transformations that have occurred in biology in the last fifty years. These transformations are often unknown by the general public, as if molecular biology had remained stalled around the double helix. But the return of the question "What is life?" is also the result of events that have occurred outside biology, of a general evolution of ideas that we will undertake to investigate." M. M. Michel Morange is a biologist, and professor at the University of Paris-VI, and at the École normale supérieur. He is director of the Centre Cavaillès d'histoire et de philosophie des sciences. He is the author of La Part des gènes [The Misunderstood Gene]. 

PART ONE

THE DEATH
AND RESURRECTION OF LIFE

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CHAPTER I

The Twilight of Life

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The expression “twilight of life” was first used in 1935, in an article that appeared in the New York Times, to summarize the implications of the crystallization of the tobacco mosaic virus (TMV) by the American chemist Wendell Meredith Stanley.1 This experiment showed that the TMV was no different from the molecules that were habitually manipulated and purified by organic chemists: it was merely a very large molecule.

Stanley’s experiment was spectacular, and it received an enormous amount of publicity. But it was only one of a number of experimental approaches that, by the middle of the twentieth century, had succeeded in depriving organisms of their mystery and substituting in its place the chemistry of macromolecules. Thirty years later a sequel to Stanley’s discovery attracted nearly as much media attention. In 1967, using only simple molecules, the American biochemist Arthur Kornberg managed to replicate the genetic material of a bacteriophage—a small virus that infects bacteria—in the test tube (“in vitro”) by introducing a specific enzyme.2

To understand the philosophical import of these experiments, we need to put them in the context of a long historical debate. From the seventeenth century onward, naturalists had sought to describe the function of organisms in terms of physical principles. The first mechanistic models failed to withstand the decisive test of experiment, however. The development of physiology in the middle of the eighteenth century, and the invention of the term “biology” at the beginning of the nineteenth century, were clear signs of a vitalist reaction to the simplistic reductionism of these models.3

Chemists nonetheless slowly learned first how to isolate the molecules of life, and then how to make them. Although the road that led from the synthesis of urea by Friedrich Wöhler in 1828 to the in-vitro fermentation of sugars by Eduard Büchner in 1897 was hardly straight, it pointed in a single direction. A few years later, another German chemist, named Wolfgang Ostwald, used the phrase “world of neglected dimensions” to describe the terra incognita that lay between the molecules studied by organic chemists and the complex internal structures of cells that could barely be discerned under a light microscope.4 It was this world that biologists forcibly invaded in the opening decades of the twentieth century. The characterization of metabolic pathways and the plodding, but constant, progress in the description of biological macromolecules all followed from the work of Wöhler and Büchner, which, in seeking to naturalize the functioning of organisms, began to pull down the barrier that separated the chemistry of life from that of the inanimate world. From this point of view, the crystallization of the TMV was just another step forward. But the TMV was not a mere macromolecule: it was a virus, and therefore, it was argued, an organism. Even if it was very simple, it was nevertheless on the animate side of the boundary between life and non-life. By crystallizing the TMV, Stanley had crossed this boundary and, at the same time, destroyed it.

In the early decades of the twentieth century, viruses occupied an increasingly important place in biological research. By the late nineteenth century they were considered an extremely small kind of microbe, because they passed through filters that retained other microbes. Impossible to grow in vitro, they were known to be responsible for serious pathologies in humans (influenza and polio, for example) and also for diseases in animals and plants. But while viruses attracted particular attention on account of their medical and economic interest, they were studied mainly because they were seen to be an elementary form of life.5 What is more, because of their small size and simple chemical composition, they appeared to be within reach of the most advanced physicochemical techniques. Some researchers (the Canadian bacteriologist Félix d’Herelle, for example) even thought that they were fossil traces of the first forms of life that had appeared on the planet.

The widespread interest in viruses also grew out of their resemblance to genes. Although Gregor Mendel had discovered the laws of genetics in 1865, he had not given a name to the “thing” that enabled characters to be transmitted, nor had he suggested what it might be made of. The reification of the gene, as it might be called—its transformation into an object that could be studied using physical and chemical tools—did not begin until 1910, when Thomas Hunt Morgan’s group at Columbia University demonstrated that genes are linked to chromosomes.6 What made the gene interesting was not only its role in determining characters, but also its capacity for self-replication, which seemed analogous to the capacity for reproduction observed in organisms. At the same time, the gene, like the virus, was sufficiently small that its physicochemical properties could be studied.7 As the smallest “unit of life,” it lay at the intersection of research by biologists on the smallest possible hereditary units within organisms and inquiry by physicists into the structure of the most complex possible molecules.8 It was therefore the ideal research object, possessing the fundamental properties of life (self-replication and variation) in their simplest form. In 1929, the American geneticist Hermann Muller put forward the hypothesis that genes form the basis of life itself.9

The realization that viruses and genes shared a number of salient characteristics—their ability to replicate themselves with variation, their small size, and what was assumed to be their critical role in the earliest phases of life—had already led Muller, in 1922, to propose that viruses (in particular, bacteriophages) were pure genes.10 This identification gave further impetus to the study of viruses, and lent even greater importance not only to Stanley’s experiment on the TMV, but also to research on the bacteriophage being carried out at about the same time by the German-born physicist Max Delbrück.11 There is a striking contrast, however, between the impact of Stanley’s experiment, which helped to expel the last vestiges of vitalism from biology, and the discreet and almost simultaneous movement away from the idea that viruses were a suitable model for the study of organisms. Viruses, it gradually became clear, are obligatory parasites—simple forms of life that use the machinery of host organisms to reproduce themselves. The decline of the virus model occurred in stages. The first doubts were raised in the mid-1930s, at the same time that Stanley succeeded in isolating the tobacco mosaic virus.12 The problem was that, despite a great many attempts, it proved impossible to cultivate viruses in any non-living medium. With greater insight into the fundamental molecular mechanisms of life came a better understanding of the reasons for the strict parasitism of viruses, which were discovered to be nothing more than packets of genetic information protected by a more or less complex envelope of proteins. Viruses have neither the necessary molecular machinery to read this information nor a metabolism capable of constructing such machinery.

The “twilight of life”—the widespread expectation that life’s mystery would finally be dispelled with the unlocking of its secrets—was thus in fact a twilight only for objects that, because they are not autonomous and do not have the extraordinary ability to synthesize chemicals, lack the distinctive characteristics of life. This paradox evaporates, however, if we introduce a distinction between “replication” and “reproduction” that does not arise in the common use of these two terms, and that has been obscured further in recent decades by the genocentric view of the living world promoted by the British ethologist and evolutionary biologist Richard Dawkins.13 To replicate is to make a faithful copy of an object. Photocopies are a form of replication. The duplication of a DNA molecule into two daughter molecules is likewise a process of replication. On the other hand, reproduction in the biological sense implies the existence of a complex autonomous organism and its participation in the creation of a second organism that is similarly autonomous. The term “reproduction” therefore refers to a complex process involving entities with complex structures and functions.

In the case of both viruses and genes, only the term “replication” is appropriate; “reproduction” implies an autonomy that neither one possesses. Confusing these terms—and the distinct processes they describe—has had one very significant consequence, namely that the reproduction of organisms is often reduced to the replication of the molecules that form them. In retrospect we can see that the momentary importance of viruses in the explanation of organic phenomena was due to a “hard” form of reductionism that denies the possibility that characteristics or functions may require a certain...

Table of contents

• Cover Page
• Title Page
• Copyright Page
• Contents
• Preface
• Part one - THE DEATH AND RESURRECTION OF LIFE
• Part two - THE QUESTION IN HISTORICAL PERSPECTIVE
• Part three - CONTRIBUTIONS OF CURRENT RESEARCH
• Part four - A FEW NECESSARILY PROVISIONAL CONCLUSIONS
• Conclusion
• Notes
• Bibliography
• Index