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The Way of the Cell: Molecules, Organisms, and the Order of Life

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This is an excellent book of detailed biological philosophy that is often a sheer delight to read. I guess the best comparison I can think of off the top of my head is to Lewis Thomas' thought provoking "Lives of a Cell," but with extremely current science. This is particularly welcome in these days when we are being inundated with the pros and cons of genetics, the emphasis here is off of the genome itself and onto its role in constructing the cell and bringing life into being.

The cell is, to put it simply, the basic unit of life. This beautifully written book investigates the principles of what science knows about the cell, and also their limits. In so doing, it also investigates much of what we know about life. While it gets very detailed at times, it is still quite readable by educated non-specialists.

"Way of the Cell" makes judicious and consistent use of current state of the art principles such as self-organization, self-assembly, and the dynamics of far from equillibrium reactions, yet it doesn't get carried away with them. This book remains solidly rooted to science throughout, even when it probes the boundaries of what we know of the complex processes in living cells.

We are treated to several very interesting, measured, and contemporary accounts of the relationship of form and function, and how cells construct themselves. The author is very much a lyrical poet of nature philosophy as well as a serious biochemist. There are also a number of insights into the history and critical observations of biological science, but the book never becomes history-heavy. It is always foremost a book of wonderment at what science tells us about life.

There is a unique discussion of the origins of life, concluding that the answer lies in the utterly remote past, but with remarkable candor admitting that without novel and powerful methods of historical inquiry, we soon reach a limit to what we can discover about it with much certainty. This is followed by an epilogue about the meaning of life, and the author's personal view that science must remain silent on matters of morality.

This is a book that brings evolution, thermodynamics, information theory, developmental biology, cell biology, and genetics into close and comfortable conjunction, and even a fair degree of synthesis in spots. There are many profound insights here to be gleaned, and even more distinctive new perspectives on old ideas. There is an awful lot of "new wine in old bottles" here in the way the authors approach each topic. There are very few extremes or excessive claims here to criticize, it just all fits together wonderfully.

This is a book that will be particularly appreciated by those who enjoy Lynn Margulis' "system" perspective on organisms, but I think it should be read by anyone interested in deep questions of the nature of life from the perspective of science.

Contents:

Schrodinger's Riddle

The Quality of Life

Cells in Nature and Theory

Molecular Logic

A (almost) Comprehensible Cell

It Takes A Cell to Make A Cell

Morphogenesis: Where Form and Function Meet

The Advance of Microbes

By Descent with Modification

So What is Life ?

Searching for the Beginning

Epilogue

Time and again in this dense, intensely scientific exposition on cellular life, Professor Harold expresses his dissatisfaction with what he calls the "genocentric" view of life. Instead he would like to see a "focus on the cellular templet rather than the molecular gene." He believes this would represent "a significant divergence from the genocentric conception of life that now dominates the scientific literature and even more so, the popular press." (p. 100) Harold makes a strong case for his point of view; indeed, it is this book more than any other that has made me see the overriding influence the immediate molecular environment has on reproduction and growth.

The genome has its "recipe," its code of instructions, but what Harold is at pains to tell us is that without the four-dimensional cellular environment in which the gene's "instructions" are carried out in a step-by-step process, there would be no growth or reproduction.

What this means is that the shape and temperature, the position and abundance of the surrounding cellular elements themselves shape the genetic expression as much as or even more than the genome. All life comes from life. All cells come from cells. There is no acting out of the genetic code outside a cellular environment.

And so we see Harold's frustration and that of other molecular biologists at all the hoopla that has accompanied the sequencing of the genome when it is clear that reading the code is just a very small step toward understanding how the cell reproduces itself and grows. What we need to understand is the intricate environment of the cell and how it interacts with the code leading to the epigenetic assembly of the cell and ultimately of the organism. The complications inherent in such an enterprise are truly mind-boggling in the extreme. Analysis of the four-dimensional factors would overwhelm the fastest computers in existence--all of them at the same time--if somehow we could figure out how to employ them to aid our analysis.

These facts explain why scientists like Harold are insistent upon a holistic approach to biology and why they again and again warn about the limitations of a reductionist approach. Life is just too complicated to be understood by breaking it down into pieces and attempting to put it back together, or to reverse engineer it.

On page 213 there is an interesting comparison of E. O. Wilson's view that there is "progress" in evolution and Stephen J. Gould's emphatic view that there is not. Harold seems to be implying that because organisms have become more complex that there is indeed at least "direction" in evolution. I would go further than this and observe that the rise of complex culture-bearing organisms like humans, who may be able to protect their home planet from a death-dealing meteor, implies if not "progress" in evolution, something equally agreeable. However, I would not say that our rise was inevitable. Indeed, along with Gould I would call it a contingency.

Much of the book, especially chapters three through eight, is a technical exploration of the microbial world of the cell using concepts and terminology not readily accessible to the lay reader. Harold is aware of this, at least for Chapter 4, "Molecular Logic," where he writes on page 35, "...students of biochemistry will find little in [the chapter]...that is new to them, but for the layman it may be like sipping water from a firehose." (!) Professor Harold provides a glossary, but one suspects one is out of one's depth when the words searched for are not in the glossary, but can be found in an ordinary dictionary!

Nonetheless the broad outlines of Harold's message can be discerned without appreciating fully the intricacies of cell metabolism and development. The introductory chapters, "Schrödinger's Riddle" and "The Quality of Life" explore the question that physicist Erwin Schrödinger famously asked in his much admired little book, What Is Life? (1944), a book that very much impressed the young Franklin Harold. In the closing chapters, beginning with Chapter 9 "By Descent with Modification," and especially the engaging Chapter 10 "So What is Life?", Harold looks more generally at evolution. He touches on the new science of complexity and how it relates to biology, and on the thermodynamics of ecosystems and how that affects natural selection. His treatment of some of the controversies in evolutionary theory is both illuminating and balanced, so much so that one would like to quote whole passages. This is obviously a subject Professor Harold has thought long and hard about for many years. Here are some examples of his thought:

"...[F]orm is not directly or rigidly determined by the genotype: the genes define a range within which the phenotype falls, but forms arise epigenetically as the result of developmental processes." (p. 209)

"Organisms are historical creatures, the products of evolution; we should not expect to deduce all their properties from universal laws." (p. 218)

"What we lack is an understanding of the principles that ultimately make living organisms living, and in their absence we cannot hope to integrate the phenomenon of life into the familiar framework of physical law. I am not here to advocate a veiled vitalism, nor to sneak in a creator by the back door. But...until we have forged rational links between the several domains of science, our understanding of life will remain incomplete and even superficial." (p. 218)

"...[W]hile a machine implies a machine maker, an organism is a self-organizing entity." (p. 220)

"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.... DNA is a peculiar sort of software, that can only be correctly interpreted by its own unique hardware.... [S]ending aliens the genome of a cat is no substitute for sending the cat itself--complete with mice." (p. 221)

The way of the cell is the way of life, for the cell is the structural unit of all living organisms on Earth. And Franklin Harold comes close to defining life in a manner that is all-encompassing, concise, and eloquent. Any person who has taken a Biology class should not have a problem with the book, although many times the author uses terminology that does not get defined at the same time, in which case, the reader has to have a good background in Cell Biology or has to browse the glossary.

Harold's eloquence is remarkable. Consider the following quotes:

1. "Over time functional systems would have "crystallized" into successful configurations, and therefore become less receptive to the import of novelty..."
2. "The genetic free-trade zone fragmented into protected enclaves, not abruptly but gradually on a time-scale of millions of years..."
3. "...leaving a huge lacuna in any account of cell evolution, but fostering a crop of stimulating conjectures."
4. "Molecular phylogenists, who draw their opinions from the bedrock of gene sequences, view the matter somewhat differently but still in a glass, darkly."
5. "The better part of valor may be to sit tight and await the tide of new data, but only dullards are proof against the temptations of myth-making."
6. "There is a fine air of whimsy, about those imaginative tales ...They also stop insouciantly around patches of quicksand, such as what brought about early cellular fusions that are not permitted to contemporary prokaryotes..."
7. "The profusion that came after is built like a fugue upon the deep theme of eukaryotic order."
8. "On the outer banks of science, one often suspects that the believer is happy while the doubter is wise; and yet, too critical a spirit is apt to overlook the genuine contribution that complexity studies have already made."
9. "The rocky path from RNA replicators to DNA genes and from catalytic RNA to protein enzymes calls for stout boots and a good head for heights."

This makes for engrossing reading, as the mystique of Biology can be overlooked when the text is dry and scholarly. There is delight, however, in reading Harold, similar to what the reader can get from Stephen Jay Gould, Richard Dawkins, and Stuart Kauffman, to name a few. I can imagine Harold entertaining his audience in a seminar with his penchant for combining words elegantly.

Today I was in a seminar where a famous molecular biologist (also a cancer biologist) admitted to a sabotage against the reductionist agenda as more scientists begin to realize that life processes cannot be just explained by the panoply of bioorganic molecules, proteins especially, and the genes that encode them. Harold fiercely stresses that DNA, for all the glorification that it deserves, is not all there is. New properties emerge as biological molecules find themselves in different cellular compartments and environments, at different stages in the development of the organism, and as the organisms themselves explore all possibilities of trading and swapping genes, and even fusing their entire bodies in one. Read this book, and be enveloped by the biological mystique!

"The typical archaeon is likely to be a lithotroph, an anaerobe, and a thermophile." (p 167)

No, the author is not addicted to Latin and Greek. His writing is colloquial and accessible. It's hard to explain, but in its context that sentence above is amusing. This book is an easygoing but fairly detailed tour of cellular life. It brings us down to the level of the cell - even the bacterial cell - and then begins to investigate how things look from that perspective.

From a cell's-eye view, big molecules are important parts of the landscape. Particular types of macromolecules and complexes have just a few (hundred or thousand) representatives, so each is important to the cellular economy. From here, it seems as if we can, almost, understand how a cell lives.

Franklin Harold shows us, in broad strokes with descents into telling detail, what he knows, and what he (and everyone else) does not know at this point about the life of cells. This book gives us a rich picture of life at the most fundamental level, and shows us, too, the puzzles that are the subjects of current research. With his pictures of cellular action, metabolism, and growth, he is attempting to answer Shrodinger's question: what is life?

We know immensely more than we used to about the details of life's machinery. But do we understand how all that intricate, mixed-up chemistry can get up and live? Harold insists that we do not, and that these questions of biochemical detail have so mesmerized us that we no longer are even asking - as if understanding emerges from a pile of facts.

Franklin Harold's motivation is not lack of interest in these details (they occupied him during his years of research), nor an anti-scientific despair that says life can only be understood in some holistic and intuitive way. Rather, it is in the spirit of what is now called Complexity Theory (and used to be called General Systems Theory). Life seems to be an emergent property of the complex system we call the cell, whose many interacting parts we more or less understand if we think about them in isolation, but whose real-time interactions are too complicated and involve too much feedback to be grasped directly.

He pursues this question, too, in reviewing the current state of science as it investigates the origin of life. His agnostic, but still hopeful, take on much of the rather vaporous speculation that fills in for any real results in this area rather appeals to me.

This book is the best sort of popular science: it gives plenty of hard fact and cogent reasoning, but avoids the trap of exhaustive textbook detail. It is a surprisingly slow read: although the author is skilled at telling us what we need to know, he is reasoning along with us about fundamental matters that are part of the dialectic of current research. When you finish this book you will feel that you have been given a straight shot of some of the heady brew that biologists these days are imbibing.

I was educated as a scientist with a focus in biochemistry. Later, I moved on to business and then psychology. I have a good background in comparative religion and philosophy as well, so this book was particularly interesting to me.

The first thing that I liked was Franklin Harolds ability to explain often difficult concepts in an understandable and interesting way. This is often an obstacle to lay readers and he makes this trek as painless as possible. Without understanding some fundamental concepts of biochemisty and living systems theory, it is difficult to look deeply at the main topic which is "what is life."

This book is an imaginative, but scientifically rigorous look at the nature of life. It is not, however, a simple reduction of life to physical and chemical processes. While it draws on these areas, it also invites the imagination to reach further and ponder deeper questions. Whether these will eventually be understood by science remains to be seen, but for not even at the frontiers of scientific knowledge there is much that is still a deep mystery.

This book focuses heavily on the life processes of bacteria as a means of understanding life. This is a simpler system than a eukaryotic (non-bacterial cell with a true nucleus) to consider and I think this is helpful because technically a bacteria is the smallest unit of life. (Viruses are not living things, but rather supermolecular complexes.)

The reader who invests the time to read this fine book will be rewarded by an expansion of his or her mind. It will ignite the imagination of even the most well-read people and yet is accessible to any intelligent laymen who has the patience to slow down and digest some of the foundational concepts.

I highly recommend this book. It is extremely thought provoking.

Recently, an unhappy swarm of scientists or science writers has emerged. Their aim is stamping down the idea that genes are the root of life's processes. They rail against "reductionist science", while extolling life's "marvels" and "mysterious" attainments. It's a curious phenomenon, sometimes comprehensible in its aims, but always flawed in its foundation. The theme counters "the narrowly focussed and reductionist science", although those holding such views remain nameless. Franklin Harold is a member of this swarm, and this book is one attempt to lift the "meaning of life" to some perceived "higher plane". The result is a highly informative description of cellular structures and processes.

Harold's method is at least shorn of the polemics used by some of his colleagues. He wants us to understand that Schrodinger's great question, "What Is Life?" has an evident response. "Note the birds and the butterflies", if you truly want to know about life, Harold urges. To him, life is something to be celebrated, to have "meaning". His view, then, is limited to the individual organism, even if it's a micro-organism. Cells, he advises, offer a view of life providing a grandeur of its own. Micro-organisms, he stresses repeatedly, have been overlooked or poorly considered in recent years. With this book he seeks to restore them to their proper place in science's realm. In doing so, he attempts to detach Darwinian natural selection from the processes that form cellular structures. He comes dangerously close to proposing the steps in building a cell cannot be derived. They are too complex and generated by processes not linked to the replication process of DNA itself.

Harold's model cell is the famous [or infamous, depending on your digestive health] Eschericaria coli, resident of your gastro-intestinal tract. He even offers a detailed "recipe" of what comprises this bacterium with an illustration of its innards. In explaining some of the complex activities present in this bacterium, he offers a new concept to biology - the field. Admitting up front that such an ephemeral process will seem alien to biologists and physicists alike, he offers it as an explanation for the paths he fails to find leading back to the genome. While he struggles to give status to his idea, the reader can only wonder at Harold's evident desperation in offering it. That we don't yet know all the steps that a cell's DNA initiates to accomplish building an organism is hardly justification for such a flimsy thesis. Again, he is but one step from the supernatural, although avidly denying the charge.

In conclusion, Harold lopes back in time to examine some of the theses addressing life's origins. He rightly offers this as science's primary issue. Accepting that life "arose from inanimate matter", he synopsizes the evidence and considers the theories. Stanley Miller's "soup" is described, and Christian de Duve's "proto-metabolic web" is examined. He gives Cairns Smith's clay template for building replicating molecules a brief phrase, then considers Gunter Wachtershauser's foundation of iron pyrites at some length. He doesn't admire any of them, because they bring him too close to what he wishes to avoid - if we understand the simple beginnings, then we can assess how complexity arose. Since Harold can't accept any of them, we are left with our own preference, or none.

In building his case against a "biochemical view of life", Harold provides a wealth of exquisite detail about cells. Enhancing this catalog of cell parts and mechanisms are some fine diagrams, some derived from microphotographs. Each of the complex images provides valuable information even the specialist will find useful. Harold's "References" is an impressive list at first glance, but a close look reveals some unwarrented gaps. The book is worth a close reading [or more!], but must not be allowed to stand alone. Because it can't. [stephen a. haines - Ottawa, Canada]

Times are changing and the rapid increase in our knowledge of the biochemistry of life needs the kind of upgrade we find in this charmingly written and quietly innovative paradigm buster whose opening question is that of the physicist Schrodinger, 'What is Life?' Leading us through a considerable tapestry on the way to its answer, the author points to a biology beyond that we have inherited from the past, and ends the book with an honest confession of the irresolvable enigma in this question. The suggestion of the need for a theory of morphogenesis in the discussion of the complexity of cellular genomics is a harbinger of a much to be hoped-for liberation from the current baffling nature of most books in this field, whose technical complexities seem cover for pulling one's leg with the magic of random self-assembly. Evolution is on the move.

Books like this are important! In this book, the author describes numerous examples of known ways that living processes operate and are controlled. In doing so, he refutes the common idea that God controls everything all the time like some grand micromanager and shows how natural processes in living systems are operating based on their own inherent properties - without the need for intervention by God all the time.
With such a realistic basis, we can then deal with the chaos and cruelty found all around us without having to twist theology around to deal with God not being the source of the suffering and cruelty in this world, past, present, and future.
The author obviously knows how living processes work and deals very well with making his text readable for many people.

The Way of the Cell: Molecules, Organisms and the Order of Life written by Franklin M. Harold is a well-written book that helps us understand why the search for answers of the riddle "What is Life?" is one of the noblest quests. This book is not about biology, biochemistry or any other finished and finite discipline, but about life.

This book deals with what are a recognizable set of properties, to identify the essential features that distinguish living organisms from other things. That riddle embraces and transends the subject matter of all the biological sciences, and much of the phyical science as well. Now, you maybe wondering, is this book too much for the non-scientific? If you have had science in high school, you should be able to figure out this book, which touches on subjects of biology, chemistry, biochemistry, and microbiology. This book is superbly written and very accessible in its explanation making the reader an observer of science so you can understand better what the scientists are working on.

So, what is the realtionship of living things to the inanimate realm of chemistry and physics? As you read on in this book, you'll find out and understand this realtionship. How can molecular interactions account for their behavior, growth, and reproduction? Living things differ from non-living ones most pointedly in their capacity to maintain, reproduce and multiply states of matter charactered by extreme degree of organization.

This book works with research on E. Coli, though a simple organism, it manifests well the example of life, the cell is a unitary whole. This book works with a vivid picture of the cell as opposed to the sub-celluar level of the gene. Heredity is in the genes, but life is in the cells.

If you have ever wanted to know the answer posed by Erwin Schrodinger, "What is Life?" read this book as some of this question will be answered. Other authors to read are: Stephen Jay Gould, Ernst Mayr, and E.O. Wilson are only just a few. This book has a very well appointed bibliography and your reading can start from there. You'll find this book to be an extremely witty, comprehensive and up-to-date work.

"The Way of the Cell: Molecules, Organisms, and the Order of Life" by Franklin Harold
Excellent book. His knowledge of cellular biology is disarming. The book may not be best for the layman, since he is not shy about using long sentences with many technical terms. But for those with enough biology under their belt, the effort to read this book is paid back handsomely. I often wish I could find someone who has read hundreds of scholarly articles, and can condense them while still preserving the nuances, especially the often neglected difference between what researchers have measured from what they have supposed. Professor Harold is such a person. I regularly found myself saying, oh, so that's what we actually know...

A case in point is what molecular biology can and cannot say about the evolution of life on Earth. If you read only Time Magazine articles you might think that since the molecular biologists have gotten involved the details of the tree of life are all sown up. But now reading about the actual experiments and the results, I found that Molecular Biology has shown what paleontology has shown. That all life has much in common. Some creatures are more closely related than others. But there are no smooth transitions between species. And in most cases entire groups of Classes, even Phyla appear out of nowhere and are subsequently weeded out. (In other words, the exact opposite of what Darwin's original theory states.)

Professor Harold has a great gift for presenting complex sets of data and associated analysis. He also seems to be talking out of both sides - though in a way I found endearing. By both sides I mean he will start a section with something like "we know that any molecular mechanisms must have arisen from random, blind variations..." and then by the end of the section he has very clearly presented a biological situation that could not have arisen in many ages of the universe, and will end with something like "...it seems we do not yet understand all the mechanisms involved in the creation of new biological forms."

--Michael Clarage