The Century of the Gene

by Keller

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 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.

Genres: Science, Biology, History Of Science, Genetics, Philosophy, Academic, Nonfiction

192 pages, Paperback

First published October 2, 2000

Reviews

[Campbell Rider]

covers very similar ground to her other book (Refiguring Life) but with more focus on genetics and some of the actual science behind it.

The key point of the book is to show that the 'gene' as concept did not really solidify until the beginning of the 20th century with the rediscovery of Mendel's work (Mendel, of course, never used the word 'gene', and Darwin talked about 'gemmules'), and has since been so complicated by new discoveries that it really ought to be retired, especially because of the misleading impact it has on the public's understanding of genetics. Even before Crick & Watson discovered the structure of DNA it was clear that organisms carried some stable mechanism of inheritance, and that perhaps if we could uncover its structure we would have the recipe, structure, blueprint, programme whatever of each living thing.

The simple genetic programme story was almost immediately undermind by the discovery of the complexity of gene expression. A succinct description of the issue is that whereas the 'genetic programme' thesis assumes a one-to-one relationship between code and protein, in actual fact the correspondence is more one-to-many or even many-to-many (this point is taken up quite nicely by a contemporary philosopher called Dan Nicholson, who argues that we can't interpret living things as organic machines partly because machines have quite specific input-output specifications – engineering metaphors lead us to try and find the same mappings in the living world, where it's actually much less straightforward) .

Put simply, the same string of nucleotides can be translated as any number of different proteins via the intervention of signalling and expression factors (for instance, by copying only two sections of the strand and then gluing them together after transcription). Genes are fairly mix-and-matchable, which helps explain how very different organisms can have nearly the same genome. (Keller recounts how researchers spliced the genes responsible for differentiating human cells into eyes into the tissues on the wings of flies – the flies grew eyes on their wings, (weird), but they were perfectly formed fly eyes, not human ones. So the gene that says 'build an eye' actually has the effect of inducing other genes to begin eye construction, and what those genes are varies from organism to organism.)

All of this leads to the conclusion that it is difficult to specify what exactly a gene is. It's now widely accepted that it's problematic to talk deterministically about the gene 'for' something, but when we have genomes, mRNAs, transcription factors, all interacting to express a genetic message, it becomes hard to pin down where exactly that message is (we certainly can't say reductively that it's just 'in' the genome). And this poses problems for the gene-selectionist (Dawkins) attitude to evolutionary change. It's hard to say genes are the fundamental unit of selection when there's no stable concept of what they are.

Keller proposes a 'developmental programme' as opposed to a 'genetic programme' which encompasses all the various extra-genetic factors contributing to development. (My thesis supervisor was part of this conversation in the early 1990s, and argued for what he calls the 'parity thesis' – basically that any causal factor in development should be on par with every other. There's no good reason to causally privilege genetic factors. The point is a salient one, and the standard response has been to say that genes have a privileged status because they're 'informational'. But it's hard to see that as more than just a convenient metaphor that doesn't really cash out in real causal terms.)

[Aeisele · Rating 4 out of 5]

This was a really interesting look at the development of genetics, and where it is today. The chapters were structured really well: it started with an intro, then a history of a certain problem, that problem at mid-century (after the discovery of the double-helix in 1953), and where we are today. All of it very fascinating.

The most interesting aspect of the book is how she argues that natural selection does not work at the level of genes, but of the life cycle. Evolutionists assumed for a while that natural selection works on phenotype (the actual structure of the organism), and that mutations in the genotype (the "information" that does, or does not, get actualized) changes the phenotype (I think this was called the "Neo-Darwinian synthesis", but someone can correct me if I'm wrong). But with new genetics research, scientists have found that there is so much redundacy built into the development process - so that if one gene is missing or transcribed wrong, then enzymes and proteins and other genes "fill in" the gaps, like redundacy in computer programs - that mutation seems to be much more complex. In fact, it appears that what is "selected" in natural selection is no the genotype or the phenotype, but the "life cycle."

This, to me, is quite amazing, and the author is quite to the point on the implications: the word "gene," while still useful in some experimental contexts, is close to useless in how we really think about life development. There are so many other factors (enzymes, proteins, etc.) that contribute in essential ways to development that saying that our genes somehow determine who we are is completely and utterly wrong-headed.

This conclusion is really interesting to me, and I think this will be the beginning of much more reading on genetics for me - which is the best part of this book. Books that impel you to read more are always good. My only complaint with Fox Keller is that she does not temper the technical language very well. Obviously you need technical language, but you don't have to put that language in technical sentence construction - which is what she does an aweful lot.

In any case, if you're interested in really understanding the idea behind talk of genes, and where its going, read this. It's short too.

[Sharad Pandian · Rating 5 out of 5]

This book might be my gateway drug into genetics.

Keller's final position (only stated in the last paragraph of the book) is that perhaps we should move away from the term "gene" to "other concepts, other terms, and other ways of thinking about biological organization" (147) since too much is expected of it. I defer to scientists regarding this, but the history and philosohical work (of conceptual clarification) is great and accessible to the relative newcomer, so I would recommend it widely.

Here's a convenient summary she provides at the end of the book:

Before reaching its limits, the lexicon of the gene had first to be built up, and the history of genetics in the first three quarters of this century offers eloquent testimony to the versatility and strengths of that core concept. Evidence accumulated over the last quarter century, however, provides a different sort of testimony: it shows us that, even in its youth, Johannsen’s little word, so innocently conceived in the early days of this century, had had to bear a load that was veritably Herculean. One single entity was taken to be the guarantor of intergenerational stability, the factor responsible for individual traits, and, at the same time, the agent directing the organism’s development. Indeed, one might say that no load had seemed too great—as long, that is, as the gene was seen as a quasi-mythical entity. But by the middle part of the century, the gene had come to be recognized as a real physical molecule—in fact, just a bit of DNA—and here, at this point in time, the history of genetics takes its most surprising turn. Both the excitement and the triumph of the new science of molecular biology came from the remarkable evidence it provided suggesting that, incredibly enough, the gene, now understood as a selfreplicating molecule of DNA, was a structure equal to its task. Yet, with the maturation of molecular biology, the impracticality (perhaps even impossibility) of that load has become steadily easier to discern.

New kinds of data gathered over the last few decades have dramatically fleshed out our understanding of the parts played by genes in cellular and organismic processes, and in doing so they have made it increasingly apparent how far the weight of such a load exceeds what any one single entity can reasonably be expected to bear, and hence, how appropriate that it be distributed among many different players in the game of life. Indeed, even taking these burdens separately, evolution has apparently seen fit to distribute each of them among a variety of players.

Thus, for example, in Chapter 1, we saw that, by itself, DNA is not capable of guaranteeing its own fidelity from one generation to another—that it needs the help of a complex machinery of editing, proofreading, and repair. Yet more surprisingly, we have seen that such mechanisms not only maintain fidelity but also play an active role in setting the limits of fidelity, by triggering other mechanisms that actively generate genetic variability under conditions of stress. Similarly, in Chapter 2 we looked at a few of the many new phenomena that have vastly complicated not only the early picture of one gene–one trait but also the more recent picture of one gene–one enzyme. We have long known that the rate of protein synthesis requires cellular regulation, but now we have learned that even the question of what kind of proteins are to be synthesized is, in part, answered by the kind and state of the cell in which the DNA finds itself. In higher organisms DNA sequence does not automatically translate into a sequence of amino acids, nor does it, by itself, suffice for telling us just which proteins will be produced in any given cell or at any stage of development. Like the responsibility for maintaining fidelity, this work too is distributed among the many players involved in posttranscriptional regulation. The same can be said regarding the determination of how a protein functions.

Of course, all the protein and RNA molecules participating in such higher-order regulation need themselves to be synthesized and hence must in some sense be “encoded” in the DNA; moreover, awareness of this need is surely what sustains the widespread assumption of a genetic program directing the proceedings. But in Chapter 3, I argued that the assumption of a program inscribed in the DNA also requires rethinking, and I suggested in its place the more dynamic concept of a distributed program in which all the various DNA, RNA, and protein components function alternatively as instructions and as data. Indeed, I argued that the notion of a distributed program accords far better with the picture of cellular regulation and development that has emerged over the last quarter of a century than does the earlier notion of a genetic program.

Finally, in Chapter 4, I explored recent findings of extensive genetic and functional redundancy that fall outside the genetic paradigm and that, in doing so, return us to a problem of central concern to many embryologists in the early part of the century. This is the problem not of genetic stability but of developmental stability—of the conspicuous robustness of developmental processes and their capacity to stay on track despite inevitable environmental, cellular, and even genetic vicissitudes. Can the language of genetics be revised to encompass such effects, or does it need to be supplemented by altogether different concepts and terms? Engineers have developed a conceptual toolkit for the design of systems—like airplanes, for example, or computers—in which reliability is the first and foremost criterion. As such, their approach might be said to be directly complementary to that of geneticists, and I suggest that the latter might profitably borrow some of the concepts and terms developed in the study of dynamic stability to enlarge their own conceptual toolkits. (144-7)

[Craig Werner · Rating 4 out of 5]

Excellent summation of the state of genetic knowledge at the start of the new century. Obviously, things have moved along a bit since then, but Keller's approach is historical, so the book maintains its value. She does a nice job explaining why geneticists (and those working in related fields like embryology) were asking the questions they asked at particular points in the process. What's most striking is how little meaning remains in the word "gene," even as it plays a huge role in public (mis)understanding of science. The shift from reified entity to dynamic system is one that's happened in many/most fields of science and readers with just a tiny bit of patience for scientific detail will come out of The Century of the Gene knowing why.

[Paula Koneazny · Rating 3 out of 5]

Keller isn't a great stylist, but does a good job of covering the complex topic of genetics in a manner that is comprehensible for the non-scientist reader. Since I'm reading this book a dozen years after it was first published (2000), I am certain that much of what she reports here has been superseded by new research & thinking in the field. I am curious about that, in the same way that I'm curious about developments in cosmology post String Theory, for example. I suffer from a perpetual outdatedness exacerbated by the primitive notions about science that were inculcated in me during 12 years of Catholic education back in the 50s and 60s. Such primary instruction so often intrudes and blocks new learning (what I know about American History suffers from the same distortion). One of the more intriguing notions that I've come away with after reading The Century of the Gene is that the gene is not a thing, but a complex web of functional, regulatory & developmental processes; "What then should we count as the beginning and end of a gene?" Another is the possibility that "mechanisms for evolvability could themselves have evolved" which would be "a serious provocation for neo-Darwinian theory, for it carries the heretical implication that organisms provide not just the passive substrate of evolution but their own motors for change; it suggests that they have become equipped with a kind of agency in their own evolution."

[Robert · Rating 1 out of 5]

Though well written, Keller rehashed the obvious in this tedious and lengthy treatise of the gene. The work should have been kept more to an essay or traditional treatise rather than a full out novel. There were some good factual pieces of information within the pages, but truly nothing that is really original. I give this 2 stars, and even that is a stretch.

[Matt Heavner · Rating 4 out of 5]

This book is really a historical (and very scientific) look at the meme of the gene. I don't think the phrase meme was ever used (but Richard Dawkins was quoted/cited - just not for a meme). The book was a great review of the history of thought about "genes" in the 1900s.

[Erica · Rating 5 out of 5]

Evelyn Fox Keller is not only a genius, she is wise in a way that surpasses all understanding. I have not read this one yet, so you will buy it for me.

[Mehmet · Rating 4 out of 5]

tekrar oku.

[Harleen]

Has all background on genetics

[David · Rating 4 out of 5]

Review at my site