Overview of Keller:

Rough outline of main argument:

Biologists have assumed that:

- Genes are the fundamental units of explanation in biology – (What does she mean by this????) Here’s what I think she meant:

- All hereditary phenomena – the consistency of traits across generations, as well as the variation within and across generations – can be traced to or explained by the gene

- “The gene is the locus of structure, function and causal agency”(p. 46) – i.e., it directs all activity in the cell and is the exclusive or at the least, primary or initiating cause of all organismic traits, behavior, etc.

Or, more precisely:

- Uncovering the sequence of base pairs on the human, mouse or C. Elegans genome will allow us to predict and explain the whole organism – it’s diseases, traits, it’s similarity to other members of the species, and it’s divergence from other members of the species. (counterpoint: functional v. structural genomics)

- The role of the gene is to faithfully reproduce traits from one generation to the next (counterpoint: DNA cannot copy itself; it requires enzymes that initiate replication, correct copying mistakes, etc. Moreover, stability is itself a product of evolution; and, sometimes high fidelity of replication is not advantageous, but rather, “expensive” for the cell; so, mutability can be adaptive.)

- Genes are discrete, they are localized at one place in the chromosome (counterpoint: split genes, introns, exons, promotor regions, terminator sequences, alternative splicing, one gene – many proteins!)

- Genes they build proteins, which in turn, build elements of the cell and control organismic function (counterpoint: regulatory v. structural genes)

- Each gene builds one protein

- Removing a gene removes its function; i.e., if you take out a gene, you take out the trait (not so ! Redunancy built in)

- The genome is a “program” – it determins the process of development, such that organisms consistently develop along a prescribed pathway.

Keller “reviews important lessons from molecular genomics” – i.e., she reviews a great deal of data about the nature of the genetic material that she claims undermines all of the above assumptions.

Keller states that her object is to:

“understand how gene talk has affected the course of biological research, ... to examine th particular ways in which terms like gene, gene action, genetic program have participated in shaping the biological landscape.” (p. 139)

THE REAL PUNCHLINE:

But, it seems tht there is more that Keller up to: she means not only to examine unclear or imprecise gene talk, but also to question whether speaking of genes at all should be part of the scientific enterprise. OR, whether there are such things as genes AT ALL!

Keller says that the “gene” is a “concept in trouble,” and cites biologists and philosophers who also make claims that “there is no single fact of the matter about what a gene is,” or, “genes are not physical objects but merely concepts that have acquired a great deal of historic baggage over the past decades.” (pp. 66-67)

As one of you wrote in your critical reflection on the book, it seems that Keller is suggesting that the concept of the gene should go the way of the concept of “ether” in 19^th century physics.

This is a radical claim! IS Keller suggesting that there is no such thing as a gene? That, in the future, biologists will no longer make appeal to the concept of the gene, but rather, “the developmental program”, or “developmental stability” or, “canalization”..?

Do you think that her arguments warrant such a dramatic conclusion?

How do you think that she could have made her arguments, or conclusions more precise?

Chapter Review:

1 – DNA is not capable of guarnateeing its own fidelity of replication – it needs help from a complex machinery of editing, proofreading, and repair. Moreover, such mechanisms not only maintain fidelity, but may also set limits to fidelity fo replication

2 – The “one gene-one enzyme” model of gene action is false. Protein synthesis depends upon cellular regulation, and genes have different functions – structural, regulatory, and so on. The work of protein synthesis is distributed among many “players”.

3 - The assumption of a program inscribed in the DNA requires rethinking. It ought to be replaced with a dynamic concept of a distributed program in which all components of protein production function alternatively as instructions and data.

4 – the observation that there is extensive genetic and functional redundancy challenges the assumption that the genes control consistent developmental processes. Keller prefers the notion of developmental stability or canalization, and suggsts that the science of development might usefully borrow from engineering, etc.

Your questions:

What exactly does Keller mean by “evolvability”? It seems to me that the idea of the capacity to evolve seems problematic. Any time agency or the idea of an inanimate object having the capacity to choose to evolve for its own future benefit is employed, it makes me a bit skeptical.

Does the idea of the evolution of evolvability really challenge “neo-Darwinism”? If so, how? What is Keller’s argument here?

Keller claims that biologists know that the term genes is incorrect, that there are not genes in the traditional sense, but gene talk is still rampant in the discipline. It seems only natural, that when something is discovered to be false, or an idea has out lived its usefulness, we should stop talking in terms of that concept. The idea of "the ether" became unusable and scientists stopped talking in terms of "the ether.” Is this what Keller is suggesting about ‘gene talk”?

With respect to the first article of faith –that hereditary elements, whatever they may be, function as basic units of biology- the belief does not seem to have been warranted by data but possibly by philosophical reasons. Did this article of faith draw on any empirical data? Why did so many maintain this belief? Could one reasonably make appeal in ways to possible arguments from analogy with physics, or an argument from parsimony?

The absence of knowledge of long-term consequences is alarming in that unforeseen consequences can be horribly destructive. My question is, how does this differ from other sciences? Keller is concerned about having a complete, or at least robust, causal story for cellular activity. But do other sciences provide robust causal stories for their respective objects of inquiry?

I would argue that the public policy process, at least in the United States anyway,

is in fact robust enough to handle a certain degree of ambiguity or even vagueness

in the dialogue between scientist and layperson. This is due primarily to the fact

that what public policy is more concerned with is the practical consequences of

scientific development, and not the particular way in which scientists conceive of

certain problems in their respective areas.

Here are some questions that I had:

- What does Keller mean exactly when she says that biologists throughout the 20^th century have believed that the “gene is the core explantory concept of biological structure and function.”(p. 9) And, “The gene is the locus of structure, function and causal agency.”(p. 46) First, what exactly is she attributing to these biologists? By “locus,” does she mean “main cause,” “exclusive cause,” or...? Does she mean to say that they believed that ALL biological phenomena could be explained via the genes? Second, is this an accurate picture of the history of biology in the 20^th century?

- Keller writes that, “It is one of the great virtues of the discourse of gene action... is... that it permitted geneticists to pursue research programs so productively, and for so long, witout even a glimmer, anywhere on the horizon, of how genes act.”(p. 50) What exactly is she suggesting by this? Is she saying that scientists can and should study purportedly casual phenomena whose mechanism of action is unknown? Does this lead to productive research programs? Always? Sometimes? *(Consider, by contrast, Newton’s positing “gravity” as a cause – Leibniz thought that this was bunk – how could Newton posit a causal power whose mechanism of action he did not understand???)

- Keller has a common answer to each question in each chapter. E.g.: What is the source of genetic stability, or faithful reproduction from one generation to the next? “that stability,” she writes, “is the product of a dynamic process.” Or, in response to, What is it that genes do? Do genes produce proteins? She writes, “What protein should a gene make, and under what circumstances? And how does it choose? In fact, it does not. Responsibility for this decision lies elsewhere, in the complex regulatory dynamics of the cell.”(p. 63) This passage raised a number of questions for me. What exactly is she suggesting by saying that “responsibility for this decision lies elsewhere”? What exactly does it mean to attribute “responsibility” for “decisions” about protein production to the “complex regulatory dynamics of the cell”? Are “dynamics” responsible for things? If so, how? Does it make sense to use causal language at all in cases where some event is the product of a “dynamic”?

- Keller suggests that the notion of “gene” as the “locus of structure, function, etc.” is problematic, and should be replaced by concepts of “dynamic processes” or “distributed programs” or “developmental stability”. Yet, she acknowledges that gene talk has been enormously productive in 20^th century biology, and that genes are useful “handles” or “operational shorthand” for experimentation and intervention. She acknowleges in the final chapter of the book that vague or ambiguous scientific language has its uses. Is there a tension in Keller’s view here? And, how exactly are scientists to use the notion of “distributed program” in their research? How is such a “dynamic processes” approach to get off the ground?