In a book that promises to change the way we think and talk about genes and genetic determinism, Evelyn Fox Keller, one of our most gifted historians and philosophers of science, provides a powerful, profound analysis of the achievements of genetics and molecular biology in the twentieth century, the century of the gene. Not just a chronicle of biology’s progress from gene to genome in one hundred years, The Century of the Gene also calls our attention to the surprising ways these advances challenge the familiar picture of the gene most of us still entertain.
Keller shows us that the very successes that have stirred our imagination have also radically undermined the primacy of the gene—word and object—as the core explanatory concept of heredity and development. She argues that we need a new vocabulary that includes concepts such as robustness, fidelity, and evolvability. But more than a new vocabulary, a new awareness is absolutely crucial: that understanding the components of a system (be they individual genes, proteins, or even molecules) may tell us little about the interactions among these components.
With the Human Genome Project nearing its first and most publicized goal, biologists are coming to realize that they have reached not the end of biology but the beginning of a new era. Indeed, Keller predicts that in the new century we will witness another Cambrian era, this time in new forms of biological thought rather than in new forms of biological life.
Evelyn Fox Keller was Professor Emerita of History and Philosophy of Science at the Massachusetts Institute of Technology. She was the recipient of a MacArthur Fellowship and numerous honorary degrees.
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1. Motors of Stasis and Change: The Regulation of Genetic Stability
How can we, from the point of view of statistical physics, reconcile the facts that the gene structure seems to involve only a comparatively small number of atoms . . . and that nevertheless it displays a most regular and lawful activity-with a durability or permanence that borders upon the miraculous?
Let me throw the truly amazing situation into relief once again. Several members of the Hapsburg dynasty have a peculiar disfigurement of the lower lip ("Hapsburger Lippe") . . . Fixing our attention on the portraits of a member of the family in the sixteenth century and of his descendant, living in the nineteenth, we may safely assume that the material gene structure responsible for the abnormal feature has been carried on from generation to generation through the centuries, faithfully reproduced at every one of the not very numerous cell divisions that lie between . . . How are we to understand that it has remained unperturbed by the disordering tendency of the heat motion for centuries? —ERWIN SCHROEDINGER, What Is Life? (1944)
If the Mendelian revolution marked the turning point of twentieth-century biology, then surely the Darwinian revolution was the great watershed of the nineteenth century. The realm of living organisms could no longer to be fitted into a great "Chain of Being"; it required its own figuration: more of a tree than a chain, and as much a succession of becoming as of beings. The living world became a world in time, and both its occupants and its relational structure were reconfigured as products of its evolutionary history.After the publication of On the Origin of Species in 1859, few could be found among the scientifically literate who still believed in the fixity of species. Moreover, Darwin's evolutionary theory offered his readers a mechanism for the origin and transformation of species-natural selection acting upon individual variation. Yet, for all the power of that theory, a fundamental mystery remained. If change is the essence of life, how are we to account for the remarkable stability with which, in each generation, organisms develop and grow true to the type of their particular species, and with a certainty that endures over the lifetime of that species?
Viewed from the perspective of geological time, species transform and evolve. Yet viewed from the perspective of historical time, they display an unmistakable constancy in form and function. But on this matter-on the "stability of type" (to borrow a phrase from Francis Galton) that is so conspicuously maintained over the course of generations Darwin's theory was silent. However eloquently and powerfully the theory of evolution by means of natural selection might account for changes in biological form and function occurring over eons and reflected in the geological record, it could not begin to explain the reproducibility of that same form and function over the shorter spans of genealogical time. Nor could it offer any account of the persistence of particular individual features from generation to generation, of the clearly recognizable family resemblances that are passed on from parents to offspring.
Of course, Darwin was not privy to the insights of genetics, nor could he have been. He shared with his contemporaries a belief in "blending heredity"-the view that the characteristics of an offspring are, somehow, a blend of the parents' characteristics-but he had nothing to say about how such distinctive features as the Hapsburg lip might endure without dilution. Nor could he offer any kind of answer to the dilemma that was later to plague Schroedinger: How can we understand the reproduction of individual features, generation after generation, with such fidelity as to lend them a "durability or permanence that borders upon the miraculous?"
The fact is that Darwin's preoccupations were different. Throughout his life, he focused his attention on mechanisms of transformation; the mechanisms required for conservation eluded both his understanding and, for the most part, his interest. And while he acknowledged that "our ignorance of the laws of variation is profound" and devoted considerable attention to the ways in which the variation essential to natural selection might arise, nowhere did he express concern about a corresponding ignorance of the laws of constancy.,
The task of searching for the laws of constancy-that is, of accounting for intergenerational stability-thus fell to Darwin's heirs. Indeed, the century of the gene begins with this task-or more specifically with efforts to account for the persistence of individual traits through the generations. Of course, just as with any collective endeavor, the science of genetics arose out of multiple needs and a variety of different interests, and these have been well chronicled by many historians. My focus here, in Chapter 1, is on the particular force that the search for constancy of individual traits exerted on the origins of the very concept of the gene. A crucial component of that concept, I argue, enters the history of genetics even before the word gene was coined, and it enters with the supposition that underlying each individual trait is a hereditary unit so stable that its stability can account for the reliability with which such traits are transmitted through the generations. In other words, the problem of trait stability was answered by assuming the existence of an inherently stable, potentially immortal, unit that could be transferred intact through the generations.
In the first part of this chapter, I trace the increasing hold this assumption of the intrinsic stability of hereditary elements came to have on geneticists in the first part of the century, its apparent vindication in the middle of the century, and its gradual dissolution over the last few decades. To be sure, genetic stability remains as remarkable a property as ever, and it is clearly a property of all known organisms. The difficulty arises with the question of how that stability is maintained, and this has proven to be a far more complex matter than we could ever have imagined. Furthermore, we will see that the maintenance of genetic stability turns out to be inextricably bound up with the generation of variability. Thus, in the second part of this chapter, I return to Darwin's concerns, taking up the companion issue of transformation and discussing some of the surprising challenges that new research on mechanisms of conservation pose to the simple neo-Darwinian picture of evolution by the cumulative operation of natural selection on randomly generated small mutations.
Finally, a word about the relation between the stability of "type" (that is, the stability with which organisms, in each generation, develop and grow true to the type of their particular species) and the stability of individual traits. For a long time, it was assumed that genes are as capable of explaining the development of individual traits as they are of explaining the development of whole organisms, and therefore that genetic stability sufficed to account for what I will later on in this book call developmental stability. I use the term to refer to the reliability with which organisms of a particular species undergo the passage from fertilization to maturity, generation after generation, each time reproducing a phenotype that is clearly recognizable as characteristic of that "type." Thus, while genetic stability is a property of all organisms, developmental stability is a term primarily applicable to multicellular organisms that pass through embryonic stages of development-that is, metazoan organisms. The differences between these two kinds of stability may be significant, but discussion of such differences must be deferred until after I have said more about the relation between genes and development. Accordingly, in my fourth and final chapter I return to the particular challenges raised in attempting to account for developmental stability.
EXPLAINING GENETIC STABILITY
August Weismann (1834-I9I4)-one of the great zoologists of the latter part of the nineteenth century-put the problem succinctly: "When we find in all species of plants and animals a thousand characteristic peculiarities of structure continued unchanged, through long series of generations; when we even see them in many cases unchanged through out whole geological periods; we very naturally ask for the causes of such a striking phenomenon . . . How is it that . . . a single cell can reproduce the tout ensemble of the parent with all the faithfulness of a portrait?"Z In these brief remarks, written in 1885, Weismann defined the challenge for a science of heredity-indeed, one might read the entire history of genetics as an attempt to answer the question he posed. But Weismann did more than pose the question: he also proposed something of an answer, and the form of his answer helped set the science of heredity on the particular track it would follow for the next sixty years or more.
Whatever the mechanism by which a single cell reproduces the traits of the parent, Weismann assumed the existence of particulate, self-reproducing elements that "determine" the properties of an organism; appropriately enough, he called these elements determinants. This assumption was hardly unique to Weismann-in fact, Darwin himself had hypothesized the existence of some such elements (his gemmules). The Dutch botanist Hugo de Vries, a near-contemporary of Weismann's (1848-1935), also hypothesized the existence of elementary hereditary units. As he wrote, "Just as physics and chemistry are based on molecules and atoms, even so the biological sciences must penetrate to these units in order to explain by their combinations the phenomena of the living world. 113 De Vries called his units pangens, a term he introduced in 1889 in an effort to salvage the best of both Darwin's gemmules and Weissman's determinants...
1. Motors of Stasis and Change: The Regulation of Genetic Stability
2. The Meaning of Gene Function: What Does a Gene Do?
3. The Concept of a Genetic Program: How to Make an Organism
4. Limits of Genetic Analysis: What Keeps Development on Track?
Conclusion: What Are Genes For?
Notes
References
Acknowledgments
Index
What People are Saying About This
In The Century of the Gene Evelyn Keller gathers together her considerable skills as a mathematician, physicist, historian and philosopher and applies them to the central problem of the last 100 years of biology, namely the relation of the genes to the building of an organism. The scholarship is masterly, not only because of her wide reading of the literature, but her deep, penetrating understanding of what she reads. To cap it all she writes clearly and elegantly so that the book is a pleasure to read. This is a conspicuously intelligent book.
John Bonner
In The Century of the Gene Evelyn Keller gathers together her considerable skills as a mathematician, physicist, historian and philosopher and applies them to the central problem of the last 100 years of biology, namely the relation of the genes to the building of an organism. The scholarship is masterly, not only because of her wide reading of the literature, but her deep, penetrating understanding of what she reads. To cap it all she writes clearly and elegantly so that the book is a pleasure to read. This is a conspicuously intelligent book. — John Bonner, Princeton University
Richard Lewontin
Evelyn Keller has the disturbing ability to make you think again from scratch about things you thought you had already understood. It is a long time since I have thought so hard about fundamental problems in genetics as I did when reading The Century of the Gene. — Richard Lewontin, Harvard University
Günter P. Wagner
In this elegantly written book Evelyn Fox-Keller tells the fascinating story of how the heuristic power of genetic experimentation interacts with the narrative power of the word "gene." Both are built on and reinforce each other. I never saw an equally convincing and well informed narrative on how language mediates the interaction between experimental research and its social context. — Günter P. Wagner, Yale University
Dorothy Nelkin
Genes have captured the scientific and popular imagination. But in The Century of the Gene, Evelyn Fox Keller provides us with a powerful analysis of the limits of the gene as an explanatory concept. Indeed, the success of molecular biology and greater understanding of biological development have exposed the wide gap between genetic information and biological meaning, undermining the very concept of the gene. Yet gene talk with all its historical baggage persists in shaping both science and popular perceptions. Keller argues convincingly for a new language, for new concepts that will enable us to deal with the real complexity of biological organization. This is a critically important book to be very widely read. — Dorothy Nelkin, New York University
