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In Search of Cell History: The Evolution of Life's Building Blocks
The origin of cells remains one of the most fundamental problems in biology, one that over the past two decades has spawned a large body of research and debate. With In Search of Cell History , Franklin M. Harold offers a comprehensive, impartial take on that research and the controversies that keep the field in turmoil.
Written in accessible language and complemented by a glossary for easy reference, this book investigates the full scope of cellular history. Assuming only a basic knowledge of cell biology, Harold examines such pivotal subjects as the relationship between cells and genes; the central role of bioenergetics in the origin of life; the status of the universal tree of life with its three stems and viral outliers; and the controversies surrounding the last universal common ancestor. He also delves deeply into the evolution of cellular organization, the origin of complex cells, and the incorporation of symbiotic organelles, and considers the fossil evidence for the earliest life on earth. In Search of Cell History shows us just how far we have come in understanding cell evolution―and the evolution of life in general―and how far we still have to go.
Written in accessible language and complemented by a glossary for easy reference, this book investigates the full scope of cellular history. Assuming only a basic knowledge of cell biology, Harold examines such pivotal subjects as the relationship between cells and genes; the central role of bioenergetics in the origin of life; the status of the universal tree of life with its three stems and viral outliers; and the controversies surrounding the last universal common ancestor. He also delves deeply into the evolution of cellular organization, the origin of complex cells, and the incorporation of symbiotic organelles, and considers the fossil evidence for the earliest life on earth. In Search of Cell History shows us just how far we have come in understanding cell evolution―and the evolution of life in general―and how far we still have to go.
304 pages, Paperback
First published January 1, 2014
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228 people want to read
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Franklin M. Harold
7 books6 followersEmeritus Professor of Biochemistry and Molecular Biology
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Displaying 1 - 9 of 9 reviews
November 23, 2022
The more you know about the intricacies of cellular biology, the more humbling the experience becomes. Even simple-seeming prokaryots like bacteria are not simple at all, and the eurkaryots, cells with a nucleus, are fantastically more complex. Even something that sounds like it would be straightforward, such as a membrane, is precisely constructed of multiple layers, each performing specific functions, and there are multiple perforations to allow nutrients in and waste out. Add to that organelles, each performing specific functions, and mitochondria to power everything, and it is an awe inspiring structure.
As an example, in your organs right now, cells are sensing the presence or absence of chemicals in the bloodstream. When a cell detects that more of something is needed, the precise location for the gene to make it is found along the four billion bases of the copy of DNA stored in the cell nucleus. The two strands of DNA are unwound at the correct place, and RNA polymerase binds to one of them. It reads the information between the gene’s start and stop markers and makes a copy in the form of a single strand of RNA. Some sections are not needed – the so-called junk DNA, which actually serves many purposes, but protein synthesis is not one of them, so these sections are cut out and the remaining sequence spliced back together. The modified RNA, now called messenger RNA (mRNA) is moved out of the nucleus and to a ribosome, which translates the sequence into amino acids, building a long chain of them until it reaches the stop code, and then releases the newly created string, which begins to fold in a precise way to become a protein. Many can fold in multiple ways to create different proteins, and thus 24,000 human genes can create around 100,000 different proteins.
An adult human is composed of about 37 trillion cells of 200 different types. Not all of them have nuclei – red blood cells, which are optimized for hemoglobin transport, do not, but most of them do, and your body must create new ones constantly. As Steven Vogel writes in Cat’s Paws and Catapults,
If you reject the idea of supernatural creation, all of this had to come from somewhere, and that is subject of this book. It is really written for someone with at least an undergraduate understanding of chemistry and biology, and some of the descriptions of processes left me in the dark, as in “they decarboxylate pyruvate to generate acetate, carbon dioxide, and hydrogen gas (hence the name), and couple this reaction to the production of ATP by substrate-level phosphorylation. (p. 159) Well, of course.
Nevertheless, the book repaid my efforts to keep going through the technical details to reach the points where the author synthesizes the details into an overarching explanation, where the wonders of evolution come alive. It starts with a beautiful term which I had never heard before: biopoiesis, the development of living matter from nonliving matter. Note that this is not evolution, which is concerned with descent with modification and has nothing to say about the ultimate origins of life, but biopoiesis is an inevitable concomitant in discussion of the forces which caused cells to develop the way they did long long ago. The first mystery to be confronted is that “Living things are made up of lifeless chemicals; their composition, and everything they do, is consistent with the laws of physics and chemistry. And yet there is nothing in those laws that would lead one to expect a universe that harbors life. At the head of the mystery lurk cells, the elementary units of life and the smallest entities that display all its characteristics.” (p. 6)
Although every theory of biopoiesis generates an equal and furious opposite theory, the most widely accepted hypothesis for the emergence of life from non-life is in the deep-sea warm smoker vents. These are not the more well known hot vents ejecting boiling water, but calmer alkaline vents running at around 70ºC. They precipitate rock formations pocked with tiny crevasses about the size of a cell, which may have been where the chemicals and processes necessary for life could have been concentrated until a self-sustaining reaction took place – life.
Once it had begun life was in no hurry to evolve into us. This might have been because the early earth possessed almost no free oxygen to power chemical reactions. What is now known as The Great Oxydation Event did not occur until 2.4-2.0 billion years ago.
Again with the understanding that there are multiple schools of thought, the generally accepted idea is that all life falls into three domains: bacteria, archaea, and eukaryota. It is unknown whether bacteria or archaea arose first, but cellular similarities indicate that eukaryota evolved from archaea as a form of chimera which incorporated some bacterial genes as well. In early life vertical evolution, from one generation to the next, was less important than horizontal evolution, where the early cells passed genes back and forth between each other (which bacteria still do today). It was only when life had attained sufficient stability and efficiency that it become a viable evolutionary strategy to protect the existing genes rather than continue to incorporate new ones.
I have a weakness for cleverly constructed analogies, so I found the author’s introduction to deep time helpful, “Let 1 millimeter, the thickness of a dime, stand for 1 year. Then 1 meter makes a millennium, 1 kilometer 1 million years, and the age of the earth (about 4.5 billion years) spans 4,500 kilometers, a little more than the distance between Miami and Seattle.” (p. 6) There is disputed evidence that life may have arisen as far back as 4 billion years ago, more convincing evidence for 3.8 billion, and firm evidence that by 3.5 billion years ago the dance of life was in full swing. Although evolution continued to operate, major changes did not come for a very long time. “For more than than three-quarters of life’s history, all the life that lived consisted of single-celled microorganisms invisible to the naked eye. By the time multicellular organisms appear in the geological record some six hundred million years ago, the evolution of cells themselves had largely run its course.” (p. 7)
Heredity is manifested in genes, and it is these which have come down through the ages. Genes are potentially immortal, and some of the ones we possess are very ancient indeed. As Richard Dawkins pointed out in The Selfish Gene, bodies are transient vessels whose purpose is to ensure that the great chain of gene transfer remains unbroken. Most genes do slowly change over time, although it is important to understand that it is not always in the direction of greater and greater complexity: if an environment changes so that some genes are no longer necessary they can be lost, and the human genome consists of a number of broken genes that no longer perform the functions they once did, such as one to synthesize Vitamin D. The rate of change for genes can be roughly calculated at about one per four million years, and thus we can estimate, for example, that humans and mice last shared a common ancestor about 120 million years ago.
I appreciate that author Franklin Harold stepped carefully around the many competing theories of cellular evolution, explaining his own positions but including divergent ones as well. Since direct evidence for ancient life is so sparse, scientists must use induction and references to living organisms to try to peer into the distant past. It is impressive to see how one plausible explanation after another is generated to create a complete system, only to topple like a house of cards when new evidence emerges. However, that is how science works: all hypotheses are contingent. If certainty is important to you, pick one of the many supernatural explanations and close your mind to any alternatives.
The book uses a number of excellent examples to help the reader understand the complexity – and the beauty of life at the cellular level. For example, we all know that cells divide, but I never gave any thought to what “divide” actually means:
There are places where this book is heavy going for someone without a background in the life sciences, but I am happy that the author never dumbed down his explanations just to carry the lowest common denominator of readers along. There were parts I did not understand, but the overall grand synthesis of emerging life was profound, beautiful, and fascinating.
As an example, in your organs right now, cells are sensing the presence or absence of chemicals in the bloodstream. When a cell detects that more of something is needed, the precise location for the gene to make it is found along the four billion bases of the copy of DNA stored in the cell nucleus. The two strands of DNA are unwound at the correct place, and RNA polymerase binds to one of them. It reads the information between the gene’s start and stop markers and makes a copy in the form of a single strand of RNA. Some sections are not needed – the so-called junk DNA, which actually serves many purposes, but protein synthesis is not one of them, so these sections are cut out and the remaining sequence spliced back together. The modified RNA, now called messenger RNA (mRNA) is moved out of the nucleus and to a ribosome, which translates the sequence into amino acids, building a long chain of them until it reaches the stop code, and then releases the newly created string, which begins to fold in a precise way to become a protein. Many can fold in multiple ways to create different proteins, and thus 24,000 human genes can create around 100,000 different proteins.
An adult human is composed of about 37 trillion cells of 200 different types. Not all of them have nuclei – red blood cells, which are optimized for hemoglobin transport, do not, but most of them do, and your body must create new ones constantly. As Steven Vogel writes in Cat’s Paws and Catapults,
To begin with, proteins are not the stablest of compounds, and their stability decreases (they rot faster) as the temperature goes up….That makes maintenance mandatory. The schedule for replacement tells us a lot about an organism’s problems. The most stable structural proteins are the most persistent; the less stable soluble proteins the least...The average half-life for the proteins in an adult human is about eighty days. (p. 238-239)
If you reject the idea of supernatural creation, all of this had to come from somewhere, and that is subject of this book. It is really written for someone with at least an undergraduate understanding of chemistry and biology, and some of the descriptions of processes left me in the dark, as in “they decarboxylate pyruvate to generate acetate, carbon dioxide, and hydrogen gas (hence the name), and couple this reaction to the production of ATP by substrate-level phosphorylation. (p. 159) Well, of course.
Nevertheless, the book repaid my efforts to keep going through the technical details to reach the points where the author synthesizes the details into an overarching explanation, where the wonders of evolution come alive. It starts with a beautiful term which I had never heard before: biopoiesis, the development of living matter from nonliving matter. Note that this is not evolution, which is concerned with descent with modification and has nothing to say about the ultimate origins of life, but biopoiesis is an inevitable concomitant in discussion of the forces which caused cells to develop the way they did long long ago. The first mystery to be confronted is that “Living things are made up of lifeless chemicals; their composition, and everything they do, is consistent with the laws of physics and chemistry. And yet there is nothing in those laws that would lead one to expect a universe that harbors life. At the head of the mystery lurk cells, the elementary units of life and the smallest entities that display all its characteristics.” (p. 6)
Although every theory of biopoiesis generates an equal and furious opposite theory, the most widely accepted hypothesis for the emergence of life from non-life is in the deep-sea warm smoker vents. These are not the more well known hot vents ejecting boiling water, but calmer alkaline vents running at around 70ºC. They precipitate rock formations pocked with tiny crevasses about the size of a cell, which may have been where the chemicals and processes necessary for life could have been concentrated until a self-sustaining reaction took place – life.
Once it had begun life was in no hurry to evolve into us. This might have been because the early earth possessed almost no free oxygen to power chemical reactions. What is now known as The Great Oxydation Event did not occur until 2.4-2.0 billion years ago.
Again with the understanding that there are multiple schools of thought, the generally accepted idea is that all life falls into three domains: bacteria, archaea, and eukaryota. It is unknown whether bacteria or archaea arose first, but cellular similarities indicate that eukaryota evolved from archaea as a form of chimera which incorporated some bacterial genes as well. In early life vertical evolution, from one generation to the next, was less important than horizontal evolution, where the early cells passed genes back and forth between each other (which bacteria still do today). It was only when life had attained sufficient stability and efficiency that it become a viable evolutionary strategy to protect the existing genes rather than continue to incorporate new ones.
I have a weakness for cleverly constructed analogies, so I found the author’s introduction to deep time helpful, “Let 1 millimeter, the thickness of a dime, stand for 1 year. Then 1 meter makes a millennium, 1 kilometer 1 million years, and the age of the earth (about 4.5 billion years) spans 4,500 kilometers, a little more than the distance between Miami and Seattle.” (p. 6) There is disputed evidence that life may have arisen as far back as 4 billion years ago, more convincing evidence for 3.8 billion, and firm evidence that by 3.5 billion years ago the dance of life was in full swing. Although evolution continued to operate, major changes did not come for a very long time. “For more than than three-quarters of life’s history, all the life that lived consisted of single-celled microorganisms invisible to the naked eye. By the time multicellular organisms appear in the geological record some six hundred million years ago, the evolution of cells themselves had largely run its course.” (p. 7)
Heredity is manifested in genes, and it is these which have come down through the ages. Genes are potentially immortal, and some of the ones we possess are very ancient indeed. As Richard Dawkins pointed out in The Selfish Gene, bodies are transient vessels whose purpose is to ensure that the great chain of gene transfer remains unbroken. Most genes do slowly change over time, although it is important to understand that it is not always in the direction of greater and greater complexity: if an environment changes so that some genes are no longer necessary they can be lost, and the human genome consists of a number of broken genes that no longer perform the functions they once did, such as one to synthesize Vitamin D. The rate of change for genes can be roughly calculated at about one per four million years, and thus we can estimate, for example, that humans and mice last shared a common ancestor about 120 million years ago.
I appreciate that author Franklin Harold stepped carefully around the many competing theories of cellular evolution, explaining his own positions but including divergent ones as well. Since direct evidence for ancient life is so sparse, scientists must use induction and references to living organisms to try to peer into the distant past. It is impressive to see how one plausible explanation after another is generated to create a complete system, only to topple like a house of cards when new evidence emerges. However, that is how science works: all hypotheses are contingent. If certainty is important to you, pick one of the many supernatural explanations and close your mind to any alternatives.
The book uses a number of excellent examples to help the reader understand the complexity – and the beauty of life at the cellular level. For example, we all know that cells divide, but I never gave any thought to what “divide” actually means:
Take E. coli, that workhorse of biochemistry and molecular biology, and of all living creatures the one best understood. A single cell takes the form of a short rod, a cylinder some 2 micrometers long and 0.8 wide, with rounded caps. Under optimal conditions, 20 minutes suffice for each cell to elongate, divide, and produce 2 where there had been 1 before. But what a prodigious task this is! In that brief span of time the original cell will have produced some 2 million protein molecules, potentially of 4,000 different kinds; some 22 million lipid molecules, composing 60 varieties; 200,000 molecules of various RNAs; and nearly 1,000 species of small organic substances, some 50 million molecules in all. (p. 19-20)
There are places where this book is heavy going for someone without a background in the life sciences, but I am happy that the author never dumbed down his explanations just to carry the lowest common denominator of readers along. There were parts I did not understand, but the overall grand synthesis of emerging life was profound, beautiful, and fascinating.
December 14, 2016
The search for cell history is an ongoing journey and this author does a great job of laying out the things we think we know pretty well, as well as discussing the strengths and weaknesses of conflicting hypotheses of the murkier issues. The writing goes from scientifically technical to down right poetic in places, which made it enjoyable to read. I would suggest a reader have some biology education or organic chemistry to not feel overwhelmed but it wasn't so technical that this lowly Bio undergrad felt lost. This book really covers a vast range of knowledge and brings it all together in one well thought out and readable package.
I perhaps could have done without the last few pages on the philosophical musings on the meaning of life itself but I can see how, once you follow that rabbit hole so far down in the search of the origin of life, it expands out into a cosmic question of the meaning of life.
I perhaps could have done without the last few pages on the philosophical musings on the meaning of life itself but I can see how, once you follow that rabbit hole so far down in the search of the origin of life, it expands out into a cosmic question of the meaning of life.
August 23, 2022
I love a book that will tell me what we don’t know. Harold beautifully lays out the state of the science of the origins of life and cell evolution, but clearly marks the boundaries where speculation begins. He acknowledges the uncertainties surrounding the earliest branches of life and whether we're looking at two or three primary branches (Bacteria, Eukarya, and Archaea). He gently questions the enshrinement of genetic information as the end-all of life's propagation, instead pointing out the extra-genetic heritability of structure inherent in the maxim of omnis cellula e cellula: all life is cells (sweeping viruses under the rug for the moment), and all cells came from a cell, which also passed along its structural information such as membranes, cell topology, etc. with the genetic code it contains. Genes may specify phenotype, but life is also passing the unbroken chain of structural organization that permits genes to work. As Harold notes, materials, processes, and structure must arise in tandem to animate the machinery of life. Cellular organization must have been there at the beginning, not a latecomer in the story of life.
To his credit, Harold gives ample space to dissenting views, even when he does not adopt them. For instance, he details without accepting Thomas Cavalier-Smith's insistence that Archaea represents a late offshoot of Bacteria rather than an early and independent branch of the tree of life. Some readers may find fault that he is similarly open-minded in evaluating some latter-day proponents of intelligent design, although he ultimately rejects ID and hews to a naturalist approach.
However, Harold is intellectually honest enough to admit the devilish difficulties in applying the logic of natural selection to the very dawn of life: Darwin can give a satisfactory account of life's diversification though descent with variation once established, but it's much harder to see how autopoietic systems that by their nature consist of multiple interdependent components could arise before the units of selection exist. Harold doesn't state this to usher the god of the gaps in through the back door, but to point out that despite the incredible strides of biology over the previous century, the question of origins remains frustratingly open.
He does also note that the picture of evolution has complexified since Darwin's day. Rather than a smooth, linear, incremental continuum of favorable adaptations, the current view is a much messier thicket of early genetic promiscuity through lateral gene transfer, symbiosis and endosymbiosis, and saltatory bursts of innovation punctuating long periods of traditional natural selection. It seems that it takes a long time for new possibility spaces to open in the energy landscape, but once they do, there's a rush to fill them.
Harold does reflect briefly on what this new view on life means, if anything. He tenders some cautious opinions about the anthropic principle and how our universe is uniquely suited for life, without committing to any particular reason it is so (and certainly not any supernatural one). He's under no pretense that he has the answers to this but I find his openness to the biggest questions absolutely refreshing. This is an excellent read if you too are inspired by the deep mysteries of life and existence and want to understand what the world of cells has to tell us about those questions.
To his credit, Harold gives ample space to dissenting views, even when he does not adopt them. For instance, he details without accepting Thomas Cavalier-Smith's insistence that Archaea represents a late offshoot of Bacteria rather than an early and independent branch of the tree of life. Some readers may find fault that he is similarly open-minded in evaluating some latter-day proponents of intelligent design, although he ultimately rejects ID and hews to a naturalist approach.
However, Harold is intellectually honest enough to admit the devilish difficulties in applying the logic of natural selection to the very dawn of life: Darwin can give a satisfactory account of life's diversification though descent with variation once established, but it's much harder to see how autopoietic systems that by their nature consist of multiple interdependent components could arise before the units of selection exist. Harold doesn't state this to usher the god of the gaps in through the back door, but to point out that despite the incredible strides of biology over the previous century, the question of origins remains frustratingly open.
He does also note that the picture of evolution has complexified since Darwin's day. Rather than a smooth, linear, incremental continuum of favorable adaptations, the current view is a much messier thicket of early genetic promiscuity through lateral gene transfer, symbiosis and endosymbiosis, and saltatory bursts of innovation punctuating long periods of traditional natural selection. It seems that it takes a long time for new possibility spaces to open in the energy landscape, but once they do, there's a rush to fill them.
Harold does reflect briefly on what this new view on life means, if anything. He tenders some cautious opinions about the anthropic principle and how our universe is uniquely suited for life, without committing to any particular reason it is so (and certainly not any supernatural one). He's under no pretense that he has the answers to this but I find his openness to the biggest questions absolutely refreshing. This is an excellent read if you too are inspired by the deep mysteries of life and existence and want to understand what the world of cells has to tell us about those questions.
September 7, 2017
An utterly boring treatment of a potentially fascinating subject.
June 20, 2019
In total an excellent review of the topic at hand. I subtracted one star for increasing repetitiveness toward the end and the entry of personal reflections about "god and life" into the text. I am fine with the latter, but I would have liked to see it moved into its own, speculative chapter.
Otherwise highly recommended to readers with an entry-level background in microbiology.
Otherwise highly recommended to readers with an entry-level background in microbiology.
August 19, 2015
Excelente livro. Um bom estado da arte sobre o que se entende da origem da vida, origem dos metabolismos, das células e da célula eucariótica. Bem compreensivo, mas consegue deixar um conteúdo pesado leve (pra mim).
January 4, 2023
The author's conclusion is that there are too many gaps and unknowns for science ever to know much about the evolutionary paths that led to of eukaryotes (nucleated cells). But the story he tells is fascinating nonetheless; and his forty years cutting-edge research as related leaves no doubt about his clear, authoritative mastery. Caveat: readers who never studied cell biology may find the technical sections challenging.
September 26, 2020
Probably best read with an undergraduate's knowledge of chemistry and biology under your belt. With that as a caveat, this is a truly great book on the deep history of the emergence of life on earth from the first protocells more than 3 billion years ago to the explosion of eukaryotic life that leads to plants, animals and humans.
suspended
September 30, 2016Sorry for the false review I wrote previously, it was a misunderstanding of the article which led me to misunderstand the idea of the book, but thanks to Jerry A Coyne in "Why Evolution is True" and to Matt Ridley in "Genome: The Autobiography of a Species in 23 Chapters" they've made everything cleared to me, and so after finishing my Graduation Project I'll definitely come back to this book to finish it
Displaying 1 - 9 of 9 reviews