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Life Explained

Yale University Press

Chapter One

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. 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 bacterio-phage-a small virus that infects bacteria-in the test tube ("in vitro") by introducing a specific enzyme.

To understand the philosophical import of these experiments, we need to put them in the context of a long historical debate. From the seventeenth centuryonward, 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.

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. 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. 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. 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. 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. 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.

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. 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. 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. 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. 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 degree of complexity in order to be expressed, and seeks to explain them instead by reference to the structure of one or a few elementary components. In reducing the complex phenomenon of reproduction to the mere replication of macromolecules, it went unnoticed that the concept of reproduction itself had been deformed and denatured.

The reduction of life to physicochemical phenomena has had the further consequence-a very important one-of favoring research into the use of organisms for commercial purposes. It is not by accident that the development of this field, biotechnology, should have coincided with the growing domination of a reductionist conception of life.

Chapter Two

In July 2002, the American journal Science announced the in-vitro synthesis of the polio virus (more precisely, the synthesis of a nucleic acid that allows the virus to be produced once it has been inserted into a cell) from simple molecules. The news made front pages around the world.

This kind of media attention may seem rather surprising. After all, the experiment was not entirely novel. As we have already seen, similar studies of a bacterial virus had been made thirty-five years earlier. The excitement surrounding this announcement had to do instead with memories of the devastating effects of the polio virus; admiration for the technological advances in the interval that had made it possible to synthesize the virus using only information contained in data banks, without direct reference to an actual virus; and fears that terrorists, employing the same method, might succeed in once again spreading a virus that was gradually being eradicated through an ongoing and global campaign of vaccination.

But the most curious aspect of this affair (and what led me, in fact, to write this book) was the confused nature of the questions posed by both journalists and scientists regarding the study's implications. Had the experimenters actually created a polio virus? If so, had they created an organism? Was there any difference between their creation and that of the Creator? Is life inside a cell any different from life in a virus? The answers that were given to these questions turned out to be even more confused.

Already in the 1930s it had become apparent that viruses were not adequate models for illustrating the "principle" of life. And yet still today they are assumed, at least by the media, to satisfy this purpose, if only because the mere creation of a virus obliges its authors to deny that they have been playing God. The reason for this is that, beginning in the 1920s, viruses were taken to be genes, and the appearance of genes was thought to be identical with the appearance of life. Despite later developments, this genetic and informational view of life is still dominant in journalistic accounts of recent discoveries.

More than sixty years ago, in his famous essay on life and the origins of the order observed to exist in organisms, the Austrian physicist Erwin Schrödinger argued that this kind of order clearly differs from the one found in the inanimate world, which is based on statistical laws that account for the movement of particles. Schrödinger predicted that the origins of order in the living world would be discovered in the specific molecular structure of those parts of the cell that seemed to be chiefly responsible for its function: genes and chromosomes. Chromosomes were understood to be the carriers of genetic information, which was transmitted from generation to generation, enabling both the structural and functional characteristics of organisms to be reproduced.

Over the next three decades, from the mid-1940s through the 1960s, research in molecular biology provided support for Schrödinger's claims and allowed them to be precisely stated in chemical terms. The active agents in cells, as we now know, are proteins-macromolecules that act as catalysts, activating chemical reactions, receiving and transmitting molecular signals, and endowing cells with form and mobility. Proteins are formed by chaining together smaller molecules-amino acids-in a specific and predetermined sequence. This sequence is not directly transmitted from generation to generation; instead it is indirectly coded in another macromolecule, DNA. Decoding this sequence permits the synthesis of the proteins responsible for the incessant chemical transformations that take place inside the living cell, and for its reproduction. With the discovery of the simple double helix structure of DNA in 1953 by James Watson and Francis Crick, it became possible to understand the ease with which this molecule replicates itself, and also how the information needed for the precise synthesis of proteins could be contained in its nucleotides.

This new informational conception of life made it possible to understand the nature of viruses as well. Viruses generally consist of a single molecule of nucleic acid (RNA or DNA),with one or more protein envelopes that protect the genetic information during its passage from organism to organism. 3 It is this information that permits the synthesis of the enveloping proteins and of the few enzymes necessary for the replication of the genetic material. By itself a virus cannot replicate: it does not produce the energy required either for protein synthesis or for the replication of its own nucleic acid molecules; it is unable to manufacture the molecular components of its macromolecules; and it does not possess the highly complex molecular structures that allow genetic information, stored in the form of nucleic acids, to be translated into proteins. The structure of DNA and its role in coding the information needed for protein synthesis are now so familiar that we are apt to forget that the discovery of these fundamental molecular mechanisms of life came as a great surprise and source of wonder. Nothing in the many studies that have been carried out since has cast the least doubt upon the elegance and functional efficiency of these mechanisms, which have been retained by evolution to ensure the nearly exact reproduction of life forms.

It was tempting to suppose that the long-sought explanation of living phenomena had been found in the perfection of these very mechanisms-all the more so because they operate identically in all organisms. Little wonder, then, that by the 1960s Crick, Monod, and other molecular biologists were convinced that they had discovered the secret of life. To be sure, a great many details remained to be worked out, not least among them the mechanisms involved in cellular differentiation and the embryonic development of multicellular organisms, including the formation of highly complex structures such as the brain. But the constitutive principle of life had been identified: the genetic code, which is to say the rule of perfect correspondence between the structure of DNA (molecular memory) and that of proteins (the active agents of life and cellular form).

For several years this understanding was confined to the theoretical level. Then, in the early 1970s, molecular tools were developed that made it possible to modify genetic material for the purpose of altering the properties of organisms. Most experiments had the basic aim of clarifying the role of various genes in the development or the functioning of a given organism. But it was only a short step from the basic to the applied, from understanding a gene's function to modifying the genome in order to create a new type of organism. Bacteria were manipulated to produce animal or human proteins; plants were made resistant to various pathogenic agents, or to toxic substances such as weed killers; laboratory animals (especially mice) were genetically modified. The ability to modify an organism at will and to endow it with new properties (within the limits of the current understanding of gene function), and in this way to exert control over the evolution of life, was a striking indication of the progress that had been made in our understanding of the living world.

(Continues...)

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Excerpted from Life Explained by MICHEL MORANGE Copyright © 2003 by Odile Jacob . Excerpted by permission.
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