Books : reviews

Franklin M. Harold.
The Way of the Cell: molecules, organisms and the order of life.
OUP. 2001

rating : 2 : great stuff
review : 11 November 2005

This is a profound and enlightening book, illustrating what a non-reductionist biology needs to encompass.

p224. If organisms are ever to be understood as material physical entities, physics will first have to be transformed into a science of complex systems.

Harold achieves this without ever going beyond the single cell: that has sufficient complexity, self-organisation, and epigenetic features of its own to more than make his point.

p17. the cell represents the simplest level of organization that manifests all the features of the phenomenon of life.

This book is not an easy read: I found that I had to digest it slowly over a period of several months, partly because of the depth of the concepts, partly because of the sheer mind-boggling complication and detail of the subject matter. For, despite Harold claiming to have taken pains to ensure that the biology is intelligible to non-biologists (and it certainly is much more intelligible than the average biology journal paper), there is still a dense soup of technical terms, not always explained in advance. However, the effort needed to unpack this is more than worthwhile.

Harold slowly builds up his argument, by showing us cells in all their amazing complexity, subtlety, and variety.

p26. prokaryotes have evolved so as to exploit the full range of energy sources available on earth. We find among them aerobes and anaerobes, all the known kinds of photosynthesis ..., the capacity to oxidise H2, H2S and Fe2+, to reduce sulfate to sulfide and CO2 to methane, and also the machinery for nitrogen fixation.

Biology is at heart an historical science -- the evolutionary route life has taken is important.

p218. Organisms are historical creatures, the products of evolution; we should not expect to deduce all their properties from universal laws. ... We are gravely hampered by having but a single kind of life to ponder

However, at the end of Harold's argument, we see that there is more to explaining the activity of life than by reference to readings of its genetic code, and more to explaining its current form than terms of evolution alone -- function and physics also play important roles in this explanatory task.

p111. Knowledge of the genes and what they encode is nowhere near sufficient to explain how the cell elongates, divides and shortly produces a pair of rods with rounded caps. What we seek to understand emerges from the sociology of molecules, not their chemistry, and carries us into a different layer of reality. ... A growing cell is not a self-assembling set of puzzle pieces, but the product of generative processes mediated by multiple molecules, physiological pathways deployed in space. The reactions that shape a cell have, of course, a chemical dimension; but unlike their fellows in the test tube, many of them display direction, location and timing.

p224. natural selection is not the sole source of order in the living world, but complements order that arises by the self-organization of complex systems.

Harold shows how biology is the science of both informatics and of physics, in addition to being historical. It is where the laws of informatics governing genetic and other information processing devices combine with the laws of physics governing complex dynamical systems in complex phase spaces of physical structures, with its contingent events all being played out over a vast historical timespan.

p39. Transport proteins carry matter; receptors deal in information. ... The role of membranes ... is dual: they separate components while channeling the flow of matter and of information.

p52. energy is the power to do, information is the power to direct what is done

p69. Genes specify the cell's building blocks; they supply raw materials, help regulate their availability and grant the cell independence of its environment. But the higher levels of order, form and function, are not spelled out in the genome. They arise by the collective self-organization of genetically determined elements, effected by cellular mechanisms that remain poorly understood. If the genome is a kind of software, it takes for granted the existence of a particular and unique decoder.

Because of all this complexity, not to mention much evidence being lost in the mists of time, Harold does not believe that we are as near to an understanding of life as some of the more optimistic pundits. The answers are at best partial, and may always remain so.

p232. To the question, What is Life?, science presently offers two answers. The first asserts that living organisms are autopoietic systems: self-constructing, self-maintaining, energy transducing autocatalytic entities. The alternative answer proclaims that living organisms are systems capable of evolving by variation and natural selection: self-reproducing entities, whose forms and functions are adapted to their environment and reflect the composition and history of an ecosystem. The two answers are not identical, but there is substantial overlap between them; they emphasize different aspects of a rounder reality. ... The best answer we can offer at present combines both partial ones: life is the property of autopoietic systems capable of evolving by variation and natural selection.

But Harold is not dismayed by this. For, after all,

p236. the unique claim of science is not that it has all the answers but that it knows the questions, and will not compromise its commitment to the rational search for truth.

Further selected quotes:

p12. Sharp categories are generally something that we put into nature, not something we find there.

p13. No biological phenomenon can be said to be understood until we have found both its functional and its evolutionary explanation---and each of these is sure to be multilayered.

p13. even a machine is not explained by mechanical principles alone, for its construction is guided by the designer's purposes which constrain the blind operation of physical laws. In the case of living organisms, it is their hierarchical organization and their origin in the interplay of random variation and natural selection that should give pause to any radical reductionist.

p15. living things are wholly composed of molecules, and everything they do finds a mechanistic explanation in terms of the actions and interactions of their constituent molecules. But their organization into systems of mounting complexity guarantees the emergence of supra-molecular structures and activities. The more advanced the level of organization, the less informative is it to seek understanding solely in terms of their molecular constituents. It makes little sense to seek the molecular basis of hibernation because that is inherently the function of an organism (though one may hope to find genes and proteins specifically involved in hibernation).

p28. prokaryotes make up the "unseen majority" of life as judged by biomass as well as cell numbers

p28. the volume of a eukaryotic cell is typically a thousand times large than that of a prokaryotic one. ... It seems likely that the complex architecture of eukaryotic cells, especially their extensive system of endomembranes, represents an adaptation to their larger size.

p52. The diversity of regulatory devices is far greater than that of the processes which are subject to regulation.

p53. The use of multiple, unrelated, and redundant regulatory devices is quite typical; the object of the exercise is not simplicity and elegance, but to make both the activity and the production of the enzymes ... exquisitely sensitive .... Control circuits, particularly those seen in eukaryotic cells, are more elaborate than the processes which are regulated, and commonly involve many more components. ... a large share of the cell's genetic information must be devoted to the production of regulatory elements.

p58. no one has discovered a persuasive chemical connection between any particular triplet of nucleotides and the amino acid that this triplet codes for.

p61. the major source of evolutionary novelty now appears to be gene duplication, followed by progressive divergence

p73. the cellular context impinges upon the transfer of information, for the [amino acid] chain will only fold "correctly" in a medium of "appropriate" ionic composition and pH.

p93. To make [network] adaptation robust, the rates ... must be modelled as functions of the ... activity of the complex, not of the concentration of the proteins.

p101. it takes no less than forty minutes to replicate the genome; cells manage nevertheless to divide every twenty minutes, by initiating new rounds of replication before the first one has finished. Consequently a fast-growing cell ... represents two cells about to become four.

p104. A growing cell is a vessel under pressure---about 5 atmospheres in the case of E. coli, comparable to the air pressure in a racing bicycle tire.

p114. Every cell comes from a parent cell, which provides a templet upon which the daughter cell is modeled; and the parent cell's epigenetic landscape acts in concert with its genes to guide the process of reproduction. New gene products ... are generated in a context that already possesses a degree of spatial structure, and they take their places in an existing order.

p124. the cytoskeleton holds together thanks to the continuing expenditure of energy, and it is subject to frequent remodelling. ... Everything is in flux, but in a regulated purposeful manner. Neither morphogenesis nor any other cellular activity of eukaryotic cells can be understood apart from the cytoskeleton.

p142. form and function in amoeboid cells do not depend on a particular set of molecular players ... Any suite of molecules will do, so long as they can be articulated into cellular structures that support the function at hand. Form grows out of this organization of molecules, not their chemistry

p143. The continuing effort to learn how ciliates position cortical organelles during growth, development and regeneration has provided incontrovertible evidence that such patterns are not spelled out in the genome. Instead, the placement of new cellular structures is directed by existing ones: structure begets structure.

p145. structural guidance is a common mode of pattern formation ... there are many examples of modifications that are transmitted from one generation to the next, not by way of the genes but because they are linked to a cellular structure that persists through cell duplication.

p150. Dynamic systems are characteristically maintained in a state remote from equilibrium by a continuous flow of energy. ... physical systems of this kind commonly undergo spatial self-organization, with concurrent enhancement of the energy throughput ... [it] coordinates the random motions of innumerable particles over an extended territory, and may persist indefinitely so long as the supply of matter and energy lasts.

pp159-160. the fundamental patterns of metabolism, heredity and structural organization were all fixed during that vast span of three billion years when the earth was populated exclusively by microorganisms.

pp162-3. The trademark of prokaryotes is metabolic diversity. ... Where eukaryotes excel ... is in the diversity of shapes, lifestyles and adaptations, their speciality is organization.

p167. The cyanobacteria went on to generate the bulk of the atmosphere's oxygen, and became the progenitors of eukaryotic chloroplasts.

p175. in the absence of discrete organisms and lineages, evolution in its earliest stages was quite unlike that with which we are familiar: its topology had the character of a net rather than a branching tree.

p203. novelty arises from three sources: gene duplication and divergence, symbiosis and epigenesis

p205. Genes did not necessarily arise where they are found, they may have been imported. There is something disturbing about the notion that genes can be transferred from one species to another, let alone between phyla and kingdoms. It violates one's sense of organismal integrity, and calls into question the principle of a lineage defined by the vertical transmission of genes from parent to offspring. But horizontal transfer happens, on a scale that ranges from single genes to entire genomes; it represents a major source of evolutionary novelty, and a significant enlargement of the modern synthesis. One such kind of lateral gene transfer has become painfully familiar: the spread of antibiotic resistance among pathogenic bacteria. ... the genes that confer resistance ... cluster on plasmids ... that pass easily from one bacterial tribe to another.

p206. the wholesale melding of lineages ... "symbiosis"

p211. developmental plasticity widens the range of phenotypes, providing a richer assortment of variants on which selection can act. … evolution is facilitated by a cellular design that loosens the linkage between genotype and phenotype ... the key building blocks have been strongly conserved … organisms diverge by rearrangement of the regulatory circuitry. Regulation is typically mediated by proteins that are relatively unspecialized and can be fitted for new functions with a small number of mutational changes. … in eukaryotes gene transcription is controlled by multiple proteins that interact weakly with DNA and with each other; new proteins bearing additional messages can be added on and summed up with the prior ones.

p221. The informational metaphor is ... a ... half-truth ... Organisms process matter and energy as well as information; each represents a dynamic node in a whirlpool of several currents, and self-reproduction is a property of the collective, not of genes. Form, structure and function are not straightforward expression of the gene's dictates; there is more to heredity than what is encoded, and you can only go from genotype to phenotype by way of epigenetics. DNA is a peculiar sort of software, that can only be correctly interpreted by its own unique hardware. ... The informational metaphor all but ignores the multiple webs of relationships that make up physiology, development, evolution and ecology.

p222. one of the perennial topics in the literature is just what makes a system complex, as distinct from merely complicated. Formalities aside, complexity is not hard to recognize and is commonly more a matter of degree than of kind. Diagnostic features include the emergence in the system as a whole of properties that cannot be assigned to any one of its components, invariance of the whole even though its components fluctuate, and a complementary interplay between local causes and global ones, such that each level constrains the other. Complex systems are commonly (though not necessarily) dynamic rather than static, and open to the input of energy and matter from the environment. Above all, they always display "some kind of non-reducibility: the behavior we are interested in evaporates when we try to reduce the system to a simpler, better-understood one".

pp222-3. Robert Rosen … has spelled out what the irreducibility of complex systems consists of. First, a complex system cannot be fractionated: there is no one-to-one relationship of parts to functions because one or more of the parts play several roles at once. Second, while aspects of a complex system may have simple mechanistic descriptions, there exists no such description that embraces the system as a whole. Third, even those apparently simple partial functions change over time and diverge from what would have been their behavior in isolation. For all those reasons, complex systems are in principle not wholly reducible to simpler ones, and the Newtonian paradigm cannot be applied to them.

p223. what then defines the subclass of complex systems to which organisms belong? Rosen seeks criteria that will be universally applicable to any form of life, even to life beyond the solar system or to fabricated organisms. Such criteria will be independent of any particular material incarnation, and must be drawn from those abstract principles of organization that make living systems living. …
     ... "A material system is an organism if, and only if, it is closed to efficient causation" … if f is any component of a living system and we ask what is the cause of f the question has an answer within the system. … in Rosen's view evolution is secondary: one can imagine life forms that did not evolve (e.g., fabricated ones), but evolution without life is inconceivable.