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book reviews nature genetics • volume 30 • march 2002 251 The cell is the true ‘miracle’ of evolution. The rest was relatively easy, as little had to be invented for the transition to multicellu- larity. In The Way of the Cell, Franklin Harold’s aim is to assess how far we have come towards an understanding of life, and so he rightly focuses on the life of the cell. Particular emphasis—he calls it a celebration—is placed on microorgan- isms, which he feels have not received the attention they deserve, even though they ruled the living world for billions of years and it is from them that the eukaryotic cell evolved. The other emphasis is on organization, which he regards as the basis of life, and which remains too often neglected. The author thinks that the book may be suitable for a general reader, and tries to make cell metabo- lism, protein synthesis and cell division comprehensible to such read- ers. But the description is quite standard, and some sections are very technical, like those dealing with Mitchell’s chemiosmotic ideas, the behavior of cells when shifted to an environment that does not contain amino acids, and bacterial chemotaxis. Harold questions what he regards as a seductive idea, namely that biological orga- nization is fully determined by molecular structures—he thinks it fundamentally wrong, as it disregards that the cell as a whole is necessary to create the proper envi- ronment for assembly to proceed. But we know that many key processes can occur in the test tube, like microtubule formation, actin polymerization and much of metabo- lism. The treatment of cell movement is quite dated. His discussion of cell division, which might reasonably be thought to be fundamental to life, focuses almost entirely on the mechanism of division itself in bac- teria, and the processes involved in the eukaryotic cell cycle are not even men- tioned. After all, the most recent Nobel Prize in medicine was given for progress in just this area. Yet he favors a view that sug- gests that the cell serves as a templet (not a template), which he describes as a source of configurational infor- mation on which the daughter cell organizes itself. But what exactly does this concept mean and how does it help us understand the cell? I cannot see this as a helpful idea. The essence of cell multipli- cation is that the cell grows so as to make itself twice as large, everything is doubled, and then this is divided into two daughters. Only the DNA repli- cates; the rest is essen- tially protein synthesis and interactions. He repeatedly points out that the genes do not provide a blueprint for the cell, but that is well known. It is the activity of the proteins they encode that determines the properties of the cell. But he is right in pointing out that we still have some way to go in explaining apical growth of the hyphae of fungi or the form of ciliates. He favors a dynamical systems approach to morphogenesis along the lines suggested so brilliantly by Alan Turing. I know of no case in all of biology, however, where a reaction-diffusion system like that pro- posed by Turing has been convincingly shown to generate a pattern. Have all organisms descended from a single ancestor in the distant past? How did that life begin? This remains the cen- tral problem—even mystery—in relation to understanding life. Harold would like whatever mechanism is proposed to involve compartmentation of some kind, lipid membranes perhaps. He is also sym- pathetic to the idea of an early ‘RNA world’ and also to the possible key role of thermophilic bacteria. The origin of the eukaryotic cell is claimed to be the most significant event in the evolution of life and he embraces Lynn Margulis’s sugges- tion that endosymbiotic bacteria had a central role. But he is uneasy with the idea that evolution is the result only of changes in genes. In his view, for example, spatial order does not emerge from the genetic program but from the dynamics that gen- erate morphogenetic fields. Those so- called fields, however, are no more than the result of protein interactions, which in turn are determined by the pattern and timing of gene expression. Harold claims that there are no detailed accounts of Darwinian evolution explain- ing any biochemical or cellular system. I take the opposite view and argue that he has not appreciated sufficiently the differ- ence and relation between genotype and phenotype—only DNA replicates and thereby determines the phenotype of future generations. His suggestion that membranes can effectively be inherited ignores that some of their components are proteins and hence are determined by genes. More importantly, he does not con- sider the evidence from genetic algorithms. These use the computer to generate, ran- domly, a number of solutions to a particu- lar problem. Selection of those that show some of the required properties, followed by mating and mutation repeated again and again, can yield surprisingly novel solutions. Signal transduction clearly reflects such a process. Evolution by ran- dom variation and selection is an astonish- ingly powerful process for generating complex functioning systems like the cell. All told, though the book contains some interesting comments and high- lights cells that perhaps do not get the attention they deserve, it does not really help us understand how cells function. In the end, cell biologists may indeed have to turn to more complex models, but better arguments will be required to persuade them that conventional molecular biology will not give them the answers they seek, or that Darwinian evolution cannot account for cellular evolution. Is the cell more than molecules? The Way of the Cell: Molecules, Organisms and the Order of Life By Franklin M. Harold Oxford University Press, $35.00, ISBN 0-19-513512-1, 2001 Reviewed by Lewis Wolpert Department of Anatomy and Developmental Biology, University College London, London, UK © 2002 Nature Publishing Group http://genetics.nature.com

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Page 1: Is the cell more than molecules?

book reviews

nature genetics • volume 30 • march 2002 251

The cell is the true ‘miracle’ of evolution.The rest was relatively easy, as little had tobe invented for the transition to multicellu-larity. In The Way of the Cell, FranklinHarold’s aim is to assess how far we havecome towards an understanding of life, andso he rightly focuses on the life of the cell.Particular emphasis—hecalls it a celebration—isplaced on microorgan-isms, which he feels havenot received the attentionthey deserve, even thoughthey ruled the living worldfor billions of years and itis from them that theeukaryotic cell evolved.The other emphasis is onorganization, which heregards as the basis of life,and which remains toooften neglected.

The author thinks thatthe book may be suitablefor a general reader, andtries to make cell metabo-lism, protein synthesis andcell division comprehensible to such read-ers. But the description is quite standard,and some sections are very technical, likethose dealing with Mitchell’s chemiosmoticideas, the behavior of cells when shifted toan environment that does not containamino acids, and bacterial chemotaxis.

Harold questions what he regards as aseductive idea, namely that biological orga-nization is fully determined by molecularstructures—he thinks it fundamentallywrong, as it disregards that the cell as awhole is necessary to create the proper envi-ronment for assembly to proceed. But weknow that many key processes can occur inthe test tube, like microtubule formation,actin polymerization and much of metabo-lism. The treatment of cell movement isquite dated. His discussion of cell division,which might reasonably be thought to befundamental to life, focuses almost entirely

on the mechanism of division itself in bac-teria, and the processes involved in theeukaryotic cell cycle are not even men-tioned. After all, the most recent NobelPrize in medicine was given for progress injust this area. Yet he favors a view that sug-gests that the cell serves as a templet (not a

template), which hedescribes as a source ofconfigurational infor-mation on which thedaughter cell organizesitself. But what exactlydoes this concept meanand how does it help usunderstand the cell? Icannot see this as ahelpful idea. Theessence of cell multipli-cation is that the cellgrows so as to makeitself twice as large,everything is doubled,and then this is dividedinto two daughters.Only the DNA repli-cates; the rest is essen-

tially protein synthesis and interactions.He repeatedly points out that the genes

do not provide a blueprint for the cell,but that is well known. It is the activity ofthe proteins they encode that determinesthe properties of the cell. But he is right inpointing out that we still have some wayto go in explaining apical growth of thehyphae of fungi or the form of ciliates. Hefavors a dynamical systems approach tomorphogenesis along the lines suggestedso brilliantly by Alan Turing. I know of nocase in all of biology, however, where areaction-diffusion system like that pro-posed by Turing has been convincinglyshown to generate a pattern.

Have all organisms descended from asingle ancestor in the distant past? Howdid that life begin? This remains the cen-tral problem—even mystery—in relationto understanding life. Harold would like

whatever mechanism is proposed toinvolve compartmentation of some kind,lipid membranes perhaps. He is also sym-pathetic to the idea of an early ‘RNAworld’ and also to the possible key role ofthermophilic bacteria. The origin of theeukaryotic cell is claimed to be the mostsignificant event in the evolution of lifeand he embraces Lynn Margulis’s sugges-tion that endosymbiotic bacteria had acentral role. But he is uneasy with the ideathat evolution is the result only of changesin genes. In his view, for example, spatialorder does not emerge from the geneticprogram but from the dynamics that gen-erate morphogenetic fields. Those so-called fields, however, are no more thanthe result of protein interactions, which inturn are determined by the pattern andtiming of gene expression.

Harold claims that there are no detailedaccounts of Darwinian evolution explain-ing any biochemical or cellular system. Itake the opposite view and argue that hehas not appreciated sufficiently the differ-ence and relation between genotype andphenotype—only DNA replicates andthereby determines the phenotype offuture generations. His suggestion thatmembranes can effectively be inheritedignores that some of their components areproteins and hence are determined bygenes. More importantly, he does not con-sider the evidence from genetic algorithms.These use the computer to generate, ran-domly, a number of solutions to a particu-lar problem. Selection of those that showsome of the required properties, followedby mating and mutation repeated againand again, can yield surprisingly novelsolutions. Signal transduction clearlyreflects such a process. Evolution by ran-dom variation and selection is an astonish-ingly powerful process for generatingcomplex functioning systems like the cell.

All told, though the book containssome interesting comments and high-lights cells that perhaps do not get theattention they deserve, it does not reallyhelp us understand how cells function. Inthe end, cell biologists may indeed have toturn to more complex models, but betterarguments will be required to persuadethem that conventional molecular biologywill not give them the answers they seek,or that Darwinian evolution cannotaccount for cellular evolution. �

Is the cell more than molecules?The Way of the Cell: Molecules, Organisms and the Order of LifeBy Franklin M. HaroldOxford University Press, $35.00, ISBN 0-19-513512-1, 2001

Reviewed by Lewis WolpertDepartment of Anatomy and Developmental Biology, University College London, London, UK

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