By Stuart Newman

from GeneWatch 31-1 | Jan-July 2018


Making Sense of Genes by Kostas Kampourakis, Cambridge University Press, 2017, 314 pp. DOI: 10.1017/9781316422939


Making Sense of Genes is an elegantly written book containing many refreshing insights about how the notion of the gene was developed in the late 19th century and how it is used and misused today. It has deservedly garnered several appreciative reviews noting its conceptual range and lucid descriptions of current research findings. Rather than depending on facile metaphors for gene function ("blueprints," "programs") like most other popular treatments of biology, the author, Kostas Kampourakis, deftly deconstructs them, showing why they have been adopted, but how they mislead. He convincingly shows that while the notion that there are genes "for" specific characters, such as height or aggressive behavior, is based on multiple misconceptions, the idea of genes "for" some diseases, including metabolic disorders and cancers, may have some merit, even though strict causation is rarely straightforward.

Something seems off-kilter, however, as the author navigates the worlds of biology and medicine, where genes remain the perennial touchstones, with what seems to be a vertiginous grasp on the notion. There is the "classical" gene of early breeders and hereditarians, the cytological gene of the early 20th century, and the molecular gene from the 1950s on. It becomes very clear that these are not all the same thing. Kampourakis even winds up questioning whether the concept of the gene has any continuing relevance in the modern discourse of epigenetic modifications of DNA, alternative splicing of messenger RNAs, and conditional regulatory elements. Not mentioned, though consistent with his other examples, is the wide prevalence of intrinsic disorder of proteins, by which a given gene product takes on different structures and functions in different tissues or at different stages of development. This last phenomenon might be the real deal-breaker for the idea of genes, and ultimate reason that full sense cannot be made of them.

The book's treatment is thus all too reminiscent of the 1884 novella Flatland, by E. A. Abbott, in which the narrator, A Square, inhabits a two-dimensional world. An encounter with A Sphere, who intersects and passes through Flatland, turns Square into an evangelist for the existence of Spaceland against the skepticism of his polygonal compatriots. The latter, nonetheless, have no trouble seeing through the cluelessness of the "points" who live in Lineland. Analogously, while a perceptive guide, like Kampourakis, can gesture at the inadequacy of understanding organisms via genes or their associated molecules, he cannot really explain why, or how to do better, without expanding the terms of reference.

Dimensions are missing from Kampourakis's narrative, but what are they? A major one is evolution. The author has written an entire book on the subject (Understanding Evolution, Cambridge, 2014), but it barely makes an appearance in this one. The roles of inheritable molecules in a present-day organism cannot be understood disconnected from the roles they had in the organism's ancestors. An interesting section of the book is devoted to the puzzling phenomena of gene "knockouts," experimental or naturally occurring animals in which a gene that in most members of a population might be essential and fatal if lost, is absent in an individual or family, but with no adverse consequence. In one recent study (not discussed, but similar to ones that are), a woman was identified with a nonfunctional version of a gene whose protein product is essential for cutting and pasting chromosomes following fertilization. While she was fertile (unlike mice that lack this gene) and had a healthy child, the child's chromosome break points were atypical. This indicates that gene products not normally involved in the recombination process have taken it on, but perform it differently.

In discussing such phenomena Kampourakis correctly notes that no character or function is dependent on just one gene and that others can often take over when a key one is absent, thus concluding that "the gene-character relation can be very difficult to understand" (p. 168). But without an evolutionary perspective one can miss the fact that a given gene can be required for the origination of an essential function, with further evolution serving to protect and reinforce the function by integrating other genes to its realization. In some cases, the originating gene can even be sidelined. The fact that a gene's significance can change over its evolutionary trajectory (something that has been termed "developmental system drift") is a critical aspect of making sense of that gene.

This is particularly relevant for understanding morphological characters, body parts of specific shapes and forms in animals and plants that were the main interest of both Charles Darwin and Gregor Mendel. Here the missing dimension in Kampourakis's discussion of genetics (in common with just about all other treatments), is consideration of the material properties of developing tissues. The author has helpful things to say about the multilevel causation of embryonic development, stating, for example, that "most distortions and misunderstandings of how genetic inheritance takes place have occurred because of the failure to take developmental processes into account" (p. 189). But in contrast to his general contention that gene variants or conditional activity function as enigmatic "difference makers" in impenetrably complex developmental systems, the products of some genes can in fact directly cause forms to appear in a fashion that is mechanistically straightforward. They do so by mobilizing physical forces and effects (cell-cell adhesion, molecular diffusion, tissue phase separation, and so forth) to cause embryos to form multiple layers, interior spaces, segments, appendages, buds, and branches. While genes and their products can have large effects (as the author describes) by tipping the balance in a complex stew of causation, sometimes, in concert with physics, they can act as prime movers in developmental or evolutionary transitions.

From the evidence in this book, the gene has been such an unstable and mutable notion in the century and a half since it was first advanced that one wonders whether its survival was due to its fitness as scientific concept, or if there were extraneous reasons. Plant and animal breeding were performed for thousands of years before the gene concept arose, providing us with virtually all the currently used domesticated varieties. The concept's relevance to research has been waning for some time: molecular biology has been increasingly stymied by attempts to express its findings in terms of the gene, and the elucidation of the roles of DNA and RNA in protein synthesis over the last seven decades could almost certainly have occurred without the notion. And finally, as the book describes, there are other modes of inheritance and heritable change than DNA.

I suggest that persistence of the gene idea owes a lot to its social roles. It has aided elites in dividing out-groups from one another through "scientific" racism and sexism, in separating indigenous and other traditional farmers from their agricultural resources via forced dependence on fertilizers and herbicides, and by patents, among other appropriative applications of DNA-based technologies. Kampourakis, to his credit, notes the eugenicist motivations of early hereditarians and their 20th century successors, but does not carry this part of the story to the present, including the current proposals by commercially connected academics to engineer future generations of people by CRISPR technology. Subsequent efforts at making sense of genes would benefit from incorporating these normally buried ideological and social dimensions in the historical and scientific narratives.

Stuart A. Newman, PhD, a founding member of the Council for Responsible Genetics, is a professor of cell biology and anatomy at New York Medical College and editor of the journal Biological Theory.

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