Genesis of the Gene

A review of What Genes Can't Do by Lenny Moss
(Cambridge MA: MIT Press, 2003)

Stephen L. Talbott

From In Context #11 (Spring, 2004)

Today biochemists can identify and characterize countless substances in the human body — sugars, lipids, proteins, and so on. But one type of substance — the nucleic acids of which genes are composed — is conceived in a manner radically different from all the others. This is why we would be surprised to hear someone say, “I have my father’s oligosaccharide for stubbornness” — whereas we speak of genes that way all the time. Yet oligosaccharides, like genes, are present in every living cell. “Is it possible,” Lenny Moss asks, “that two biologically ubiquitous types of molecules could be so fundamentally different that it would make perfect sense to speak of one as a determinant of, for example, one's stubborn disposition, but only humorous to ascribe as much to the other?”

Not really. And one way to summarize Moss' book would be to say that it gives thorough substance to this negative answer. Moss, a cell biologist who now teaches philosophy at Notre Dame, approaches the task with a historical sensibility. This brings him to understand that two very different genes haunt the scientific imagination. One is thought to predict the traits (or “phenotype”) of an organism. We speak of this gene when we say, “She has the gene for blue eyes” or “He is genetically predisposed to retinal cancer.” The other sort of gene specifies low-level, cause-and-effect developmental pathways. Such genes are said to provide templates for RNA and protein synthesis, but they have no clear and determinate relation to the observable traits of organisms.

We establish the presence of the first gene by finding a heritable pattern for a particular trait, and then by assigning the term “gene” to the hereditary factor — whatever it is and however complex its operation — that is presumed to account for the trait. In Moss' words, this concept began “not with an intention to put a name on some piece of matter but rather with the intention of referring to an unknown something ... which was deemed to be responsible for the transmission of biological form between generations.”

On the other hand, we pursue the second gene by using highly refined biochemical techniques to trace molecular interactions at the level of the chromosome. But between these interactions and the observable traits of an organism there lies all the unfathomable and indeterminate complexity of cell, tissue, organism, and environment. In the organic interaction and mutuality of thousands of substances in every cell, it is impossible to trace unidirectional paths of cause and effect from gene template to manifest trait — this despite the fact that researchers routinely speak as if they were articulating exactly such paths. Moss calls the gene as viewed from the molecular-template standpoint the “epigenetic” or “developmental” gene.

The central thesis of his book is that we are witnessing an unjustified conflation of these two notions in modern genetics. The resulting, composite gene, “held together by rhetorical glue,” is alone what supports the widespread belief that genes are self-contained units of information determining traits — that they are, in other words, blueprints for organisms.

Moss summarizes the conflation this way:

The empirical fruits of several decades of research in molecular, cell, and developmental biology have revealed that what distinguishes one biological form from another is seldom, if ever, the presence or absence of a certain genetic template but rather when and where genes are expressed, how they are modified, and into what structural and dynamic relationships their “products” become embedded. If genes are to be both molecules which function as physical templates for the synthesis of other molecules and determinants of organismic traits and phenotypes, then somehow genes would have to, in effect, provide their own instructions for use. They would have to be able to specify when and where their templates would be put to use, how such products would be modified and targeted, as well as in what structural and dynamic relationship they would reside. Indeed, it is just this sense of genes being able to do this which appears to be conveyed with references to genes as information, as programs, as blueprints, as encyclopedias of life, and the like.

Thus was born the “gene (or genetic program) envisaged as context-independent information for how to make an organism.” The way we speak of genes today, he goes on to say, has been determined “not by those whose hypotheses were successful but rather by those whose metaphors were successful.” And the chief aim of Moss’ book is to demonstrate the inadequacy of the hypotheses thought to undergird the gene as both marker for observable traits and precise, molecular cause of those traits.

The fact is, he argues, that “biological order is distributed over several parallel and mutually dependent systems such that no one system, and certainly no one molecule, could reasonably be accorded the status of being a program, blueprint, set of instructions, and so forth, for the remainder.” For example, cells are structurally and functionally compartmentalized by a complex network of subtle membranes. These membranes regulate the role of gene products (proteins) within the cell and organism by, among other things, controlling the movement of proteins toward different functional compartments. Yet, despite their central importance in the cell, the membranous bodies cannot be reduced to the usual terms of genetic explanation. They “constitute the necessary and irreplaceable templates of their own production and reproduction, are passed along from one generation to the next [extragenetically, via the egg cell], and provide the unavoidable context in which DNA can be adequately interpreted, that is, in which genes can be genes.”

Moss also looks at the “astronomical” complexity of self-maintaining, self-regulating metabolic processes in the cell, noting that genes can neither account for the integration and balance of these dynamic processes nor exist without them. And he also summarizes the ways in which the larger cell regulates the activity of genes through chromatin marking — the chemical modification of DNA. Then he offers a 56-page review of the long and tortuous quest for a genetic understanding of cancer. The upshot of it all is his conclusion that “the stability and intelligibility sought for in idealized genes must be rediscovered in the complex dynamics of process” — process that is always shaped by context.

In sum, Moss wishes to deliver science from the spell of the fairy tale that continues to influence genetic researchers even though its particular elements have been discarded one after another:

Once upon a time it was believed that something called “genes” were integral units, that each specified a piece of a phenotype, that the phenotype as a whole was the result of the sum of these units, and that evolutionary change was the result of the new genes created by random mutation and differential survival. Once upon a time it was believed that the chromosomal location of genes was irrelevant, that DNA was the citadel of stability, that DNA which didn't code for proteins was biological “junk,” and that coding DNA included, as it were, its own instructions for use. Once upon a time it would have stood to reason that the complexity of an organism would be proportional to the number of its unique genetic units.

One other note. Moss points out how contemporary biologists repeatedly suggest we must choose between Darwinian evolution, as conventionally understood, and creationism. But this shows a blatant disregard of history. The teleologies of Aristotle and Kant profoundly shaped the history of biological thinking, but neither Aristotle nor Kant was a creationist. “There was for Aristotle no exceptionalism, no miracles, or divine interventions.” In fact,

There were no references to external causation in Aristotle's biology at all. Aristotle labored to understand the nature of living beings in terms of the elements and movements from which they were constituted. He found in the organism's adapted form — that is, in its mode of existence and attunement to its environment — the organizing principle of the organism, its final cause or purpose unto itself, the for-the-sake-of which it undergoes its formative processes.

What has happened is that the individual organism's development and maturation — its achievement of a highly organized, complex, adapted form — has ceased to be the central problem of biology demanding explanation. Development is seen rather trivially as “the result of a preset centralized [genetic] program.” Attention is then turned to phylogenetic, or evolutionary, issues. In this way the biologist “expels all manner of adaptive agency from within the organism and relocates it in an external force — or as Daniel Dennet prefers to say, an algorithm called ‘natural selection.’”

This shift, which Moss calls the “phylogenetic turn,” conveniently allows the biologist to ignore real organisms as far as possible, and instead to play with the mathematics and logic of genetic “code,” mutations, population genetics, and all the rest. In this game, as Moss shows so well, reality is the loser.

Original source: In Context #11 (Spring, 2004, pp. 7-8); copyright 2004 by The Nature Institute