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

Rating:
Summary: Seeing the Forest And the Trees
Review: "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.

Rating:
Summary: WHAT IS LIFE?
Review: Franklin Harold's the WAY OF THE CELL, by analogies with computers and machines, leads the reader closer to understanding the relationship of the 1-D genotype to the 3-D phenotype. In English, how does the DNA blueprint lead to the finished, living organism? He shows the cell as the nanobot machine able to produce the pieces of what we call life. One of his favorite thinkers is Richard Dawkins who says genes build cellular survival machines. On P. 81 Harold tells us, "from genes to cells is a journey without maps."

So what is life? This book is an apology for man's inability to create life in a test tube. Yes, the author ends the book by throwing up his hands but the journey is still exciting. Man's attempt to create life in a test tube is merely his attempt to magnify these cellular sized wonders. By magnifying the lego pieces within the cell Harold shows that man within is filled with a billion tiny oceans teaming with life. Life must lie hidden in the currents which flow within the cellular oceans. When man can navigate these currents he will understand what life is. The author helps to reveal the wonder of this fantastic voyage.

What is life? Man knows it when he sees it. The fact that we can't manufacture life from scratch is no different than not being able to create a second sun from scratch. If life were a book of blank pages, the cell is the printing press that imprints the book with words, sentences and paragraphs. Another analogy Harold uses is that of a river of DNA flowing within cellular banks. The author warns us that analogies are only half truths. Since his book is filled with analogies, the whole truth of what life is can never be told.

Rating:
Summary: WHAT IS LIFE?
Review: Franklin Harold's the WAY OF THE CELL, by analogies with computers and machines, leads the reader closer to understanding the relationship of the 1-D genotype to the 3-D phenotype. In English, how does the DNA blueprint lead to the finished, living organism? He shows the cell as the nanobot machine able to produce the pieces of what we call life. One of his favorite thinkers is Richard Dawkins who says genes build cellular survival machines. On P. 81 Harold tells us, "from genes to cells is a journey without maps."

So what is life? This book is an apology for man's inability to create life in a test tube. Yes, the author ends the book by throwing up his hands but the journey is still exciting. Man's attempt to create life in a test tube is merely his attempt to magnify these cellular sized wonders. By magnifying the lego pieces within the cell Harold shows that man within is filled with a billion tiny oceans teaming with life. Life must lie hidden in the currents which flow within the cellular oceans. When man can navigate these currents he will understand what life is. The author helps to reveal the wonder of this fantastic voyage.

What is life? Man knows it when he sees it. The fact that we can't manufacture life from scratch is no different than not being able to create a second sun from scratch. If life were a book of blank pages, the cell is the printing press that imprints the book with words, sentences and paragraphs. Another analogy Harold uses is that of a river of DNA flowing within cellular banks. The author warns us that analogies are only half truths. Since his book is filled with analogies, the whole truth of what life is can never be told.

Rating:
Summary: Eloquent tribute to the mystique of Biology.
Review: 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!

Rating:
Summary: Eloquent tribute to the mystique of Biology.
Review: 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!

Rating:
Summary: The Way of the Cell:Molecules, Organisms & the Order of Life
Review: 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.

Rating:
Summary: Superb natural philosophy of life with very current science
Review: 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

Rating:
Summary: Difficult, profound; worth the reader's best efforts
Review: 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)

Rating:
Summary: The Mystery of Life
Review: 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.