The Way of the Cell: Molecules, Organisms, and the Order of Life. Franklin M. Harold. Oxford University Press, Oxford, United Kingdom, 2003. 320 pp., illus. $17.95 (ISBN 0195163389 paper).
The author of this book, Franklin M. Harold, is a professor emeritus of biochemistry at Colorado State University in Fort Collins. His scientific interests have centered on the physiology, energetics, and morphogenesis of microorganisms. These interests are amply demonstrated in The Way of the Cell, but the reader soon realizes that Professor Harold is engaging with the wider issues of biology, such as morphogenesis and evolution, to grapple with the nature of life itself.
Harold starts by reminding his readers of Erwin Schrödinger's book What Is Life? (1944) and the extraordinary influence it had in spreading the idea that genetic information in the cell must exist in the form of “aperiodic crystals.” Nearly 60 years later, how much better do we understand the nature of life? There can be no doubt that the composition and structure of these “aperiodic crystals” have been elucidated to a fine degree of detail. Nevertheless, Harold states that although “every biological phenomenon, however complex, is ultimately based on chemical and physical interactions among molecules,…yet, the levels of complexity of cells and organisms must be taken into account in order to understand life, the essential nature of which continues to elude us” (p. 7). Such humility is rare in today's science. The more usual attitude is exemplified by the molecular biologist Walter Gilbert, who has said that when we have the complete sequence of the human genome, “we will know what it is to be human” (Lewontin 2000).
One of the first things students learn in elementary biology is a list of the characteristics of life: fluxes of matter and energy, self-reproduction, organization, and adaptation. This list of mechanical properties, however, has to be supplemented by a more holistic outlook: Whenever a system is assembled from its constituent parts, novel properties emerge that could not have been predicted from the knowledge of those parts alone. In the contemplation of any living organism, both reductionist and holistic approaches are needed. As Harold points out, in recent years “the single-minded concentration on the relatively tractable problems of chemical structures and interactions has been accompanied by neglect of the higher levels of biological order, often to the point of absurdity” (p. 31).
After explaining his general outlook on biology in chapters 1 and 2, Harold then gets down in chapter 3 to a detailed consideration of cell types and their organization into eubacteria, archaebacteria, and eukaryotes. He also takes his readers on a concise tour of the cell. Chapter 4 presents a bird's-eye view of energetics, the gene, and protein synthesis. Presumably it was written with the general reader in mind. However, this chapter is too short to be comprehensive and too long to keep the reader's attention.
Chapter 5, “A (almost) Comprehensible Cell,” gives the author the opportunity to state the rationale for his book. After mentioning the massive compendium by Neidhardt and colleagues (1996) on Escherichia coli and Salmonella, with its 2800 double-column pages and more than 20,000 references, he adds that “the single-minded dissection to the molecular level” gives no idea of the living organism that has been “shattered into bits and bytes…. The time has come to put the cell together again, form, function and history and all.” Harold has heard the siren song of DNA and has sailed on.
Harold continues this theme in chapter 6, which deals with cell division. Taking Virchow (“every cell comes from a pre-existent cell”) as the starting point, he describes the division of the E. coli cell in some detail. Every cell provides the templet on which the daughter cell organizes itself. The continuity of cellular structure, Harold suggests, is a necessary complement to the continuity of genetic information. This is regarded as heresy nowadays in the present climate of research and in the popular press. According to the genetic paradigm, a cell's molecular composition, structural anatomy, form, and behavior are determined by its complement of genes (p. 111). But “knowledge of the genes and what they encode is nowhere near sufficient to explain how the E. coli cell elongates, divides and shortly produces a pair of rods with rounded caps. Upper levels of order can be seen everywhere” (p. 112).
I found chapter 7, “Morphogenesis: Where Form and Function Meet,” to be the most exciting of the book. This chapter describes a score of problems that science has as yet barely begun to solve: For example, how do fungal hyphae grow at the tip? How is the polarity of the brown algal oocyte established? How do amoebae control their shape? How do cells such as Paramecium become asymmetric? Also, there is a brief account of the extraordinary work of Lionel Harrison and Brian Goodwin on Acetabularia (pp. 153–154). These researchers have devised a set of more than 20 differential equations that define a morphogenetic field within the apical region of the cell that controls the growth of the umbrella-shaped cap. Elsewhere, Harold mentions morphogens: diffusible proteins in the developing embryo of Drosophila that bring about a grid of gradients.
Chapter 9 finds the author again in a combative mood as he takes a critical look at evolution. He surveys work suggesting that allowance must be made for evolutionary forces additional to the primary ones of variation and selection. He mentions Stephen Jay Gould, who was among the first to challenge the belief that evolutionary change must always be gradual. Scott F. Gilbert, John M. Opitz, and Rudolf A. Raff did research on embryology that led them to reevaluate homology and morphogenetic fields. Novelty can also be generated from gene duplication and divergence, symbiosis, and embryogenesis. The idea of epigenesis will please those researchers who, like the present reviewer, have seen moderately salt-tolerant algae become strongly halophilic when the salt concentration of the growth medium is increased. (I was sorry to see that Harold is not much impressed by work on the origins of life, and in particular that he did not mention Freeman Dyson's work on the possible origins of metabolism; but we are all entitled to our preferences.) The book ends with another look at the question, “What is life?” And now the definition Harold offers is a far broader one: Life is the property of autonomously reproducing systems that are capable of evolving by variation and natural selection.
This book seems to have been designed with the general reader in mind, but I would hesitate before recommending it to such a person. For one thing, it would take extraordinary dedication for the reader to struggle through a book whose value lies in its detail. More seriously, although the author mentions (briefly) the philosopher Mary Midgley, he has not engaged in any depth her criticisms of modern science. He ends his book by concluding that he has come to think of science “as a kind of game…. It provides no basis for ethical choice, nor the will to act.” General readers cannot, therefore, expect to find anything in this book to help them solve their own human concerns.
However, there are other potential readers who could gain immensely from reading Harold's book. Young scientists trying to decide on a field of specialization will be helped by the breadth of the knowledge evident in the book and by the balanced tone in which it is written. The author notes, “If I were a young investigator, I would not be content to bash promoter sequences; I'd want to go and look behind the ranges, where something new may be hidden” (p. 115). The Way of the Cell can act as a map to those unexplored ranges, just as What Is Life? inspired other young scientists 60 years ago.