Evolution, the Logic of Biology E-Book

John S. Torday

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 666

Veröffentlichungsjahr: 2017

Beschreibung

By focusing on the cellular mechanisms that underlie ontogeny, phylogeny and regeneration of complex physiologic traits, Evolution, the Logic of Biology demonstrates the use of homeostasis, the fundamental principle of physiology and medicine, as the unifying mechanism for evolution as all of biology. The homeostasis principle can be used to understand how environmental stressors have affected physiologic mechanisms to generate condition-specific novelty through cellular mechanisms. Evolution, the Logic of Biology allows the reader to understand the vertebrate life-cycle as an intergenerational continuum in support of effective, on-going environmental adaptation. By understanding the principles of physiology from their fundamental unicellular origins, culminating in modern-day metazoans, the reader as student, researcher or practitioner will be encouraged to think in terms of the prevention of disease, rather than in the treatment of disease as the eradication of symptoms. By tracing the ontogeny and phylogeny of this and other phenotypic homologies, one can perceive and understand how complex physiologic traits have mechanistically evolved from their simpler ancestral and developmental origins as cellular structures and functions, providing a logic of biology for the first time. Evolution, the Logic of Biology will be an invaluable resource for graduate students and researchers studying evolutionary development, medicine and biology, anthropology, comparative and developmental biology, genetics and genomics, and physiology.

Leseprobe

Evolution, the Logic of Biology

John S. Torday

Departments of Pediatrics, and Obstetrics and Gynecology

Harbor‐UCLA Medical Center, Torrance, California, USA

Evolutionary Medicine Program

UCLA, Los Angeles, California, USA

Virender K. Rehan

Department of Pediatrics

Harbor‐UCLA Medical Center

Torrance, California, USA

This edition first published 2017© 2017 John Wiley & Sons, Inc.

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ISBN: 9781118729267

Cover design: WileyCover image: © Man_Half‐tube/Gettyimages

Dr. Torday dedicates this book to his wife Barbara, his children Nicole Anne and Daniel Philip Torday, his daughter‐in‐law Dr. Erin Kathleen Torday, his granddaughters Abigail Eve and Delia Rose Torday, his parents Steven and Maria Torday, and his mentor Mary Ellen Avery.

Dr. Rehan dedicates this book to his parents Sain Das and Nirmala Rehan, his wife Yu Hsiu and children Amit and Anika Rehan, and his brother (the late) Dr. Sudhir Rehan.

Preface

We shall not cease from exploration

and the end of all our exploring will be

to arrive where we started

and know the place for the first time.

T.S. Eliot, Four Quartets

This book is a sequel to our first publication on the cellular‐molecular basis for vertebrate evolution, which was entitled Evolutionary Biology, Cell‐Cell Communication, and Complex Disease. In it we showed the utility of a cellular‐molecular approach to understanding the evolution of complex physiology from the unicellular state. In the current book, the Ur hypothesis is that all complex physiology has evolved from the cell membrane of unicellular organisms, offering a functional integration of all physiologic properties intersecting structurally and functionally in the unicellular “singularity.” This combined holistic‐reductionistic perspective provides a fundamental insight to the logic of biology never before available.

By tracing the emergence and contingence of novel evolutionary traits backwards in the history of the organism using ontogeny and phylogeny as guide posts, we have been able to deconvolute the lung as an archetype for understanding how and why physiologic traits have evolved from their unicellular origins – how cholesterol evolved from the sterol pathway of bacteria to facilitate oxygenation, metabolism, and locomotion in primitive eukaryotes, only to later recur molecularly, cellularly, structurally, and functionally as the swim bladder of fish, and subsequently as the lung of amphibians, reptiles, mammals, and birds. That “arc” has provided a way of connecting the evolutionary dots to other physiologic traits – skin, kidney, skeleton, brain – by tracing their evolution in tandem with the lung ontogenetically and phylogenetically, in combination with pathophysiologic data to provide the fullest picture for such complex, arcane interrelationships. Such interconnections become more apparent during times of stress like the water‐to‐land transition (see Chapter 2, e.g.). The specific causes of the gene mutations and duplications that occurred during that phase of vertebrate evolution, when seen in the context of having to adapt to terrestrial life, become self‐evident when factored into the prevailing physiologic constraints. This is particularly true of the developmental and phylogenetic properties that are mediated by soluble growth factors and their cognate receptors.

In brief, Chapter 1, “Introduction,” sets the stage for a paradigm shift in the way we think about the evolution of vertebrate physiology, based on mechanisms of cell–cell interactions. Chapter 2, entitled “On the fractal nature of evolution,” shows the value added in the cellular‐molecular approach to evolution, beginning with the origins of life. It is predicated on the balancing selection of calcium and lipids as the fundament of vertebrate evolution. We suggest that the cell is the ultimate physiologic fractal, expressing the “first principles of physiology.” Biology mimics the Big Bang of physics, generating its own internal pseudo‐Universe through the entraining of calcium by lipids, which is vertically integrated to generate complex physiology. Chapter 3, entitled “The historic perspective on paracrinology and evolution as lead‐ins to a systems biology approach,” traces the history of cell culture and its influence on our insights to the role of the cell in evolution. That realization was a game‐changer for our understanding of embryology, homeostasis, and repair as a functional continuum. Chapter 4, entitled “Evolution of adipocyte differentiation related protein, or ‘Oh, the Places You’ll Go’ – Theodore Geissel, aka Dr Seuss,” describes the discovery of neutral lipid trafficking within the lung alveolus for stretch‐regulated surfactant production. The realization of the paracrine regulation of surfactant phospholipid substrate provided seminal cellular‐molecular insights to the evolution of the lung and other complex physiologic mechanisms. Chapter 5, entitled “Evolutionary ontology and epistemology,” provides the rationale for reconfiguring the logic of biology and evolution. In this chapter, we delve into philosophical aspects of the cellular‐molecular approach to evolution. The identification of homeostasis as the underlying, overriding mechanism of evolution fundamentally affects the way in which we think of the process. Chapter 6, entitled “Calcium‐lipid epistasis: like ouroboros, the snake, catching its tail!,” delineates the epistatic balancing selection for calcium and lipids as the operating principle for vertebrate biology and evolution. We have gone into detail with regard to calcium/lipid epistatic balancing selection as the founding principle of eukaryotic physiology and evolution. Chapter 7, entitled “The lung alveolar lipofibroblast: an evolutionary strategy against neonatal hyperoxic lung injury,” describes the evolution and role of the lipofibroblast in lung development, homeostasis, repair, and evolution. The lipofibroblast is emblematic of lipid homeostatic balance in eukaryotic physiologic regulation. We exemplify the vertical integration from the molecular to the physiologic/pathophysiologic using the lung alveolus as a model. Chapter 8, entitled “Bio‐logic,” is a further exposition on the cellular approach to understanding the logical basis of physiology as a continuum from unicellular to multicellular organisms. The chapter looks at complex physiology as a “vertically synthetic,” internally consistent, scale‐free process, both developmentally and phylogenetically. Chapter 9, entitled “Cell signaling as the basis for all of biology,” focuses on cell–cell signaling as the mechanistic basis for all of the principles of physiology. Chapter 10, entitled “Information + negentropy + homeostasis = evolution,” explains the functional interrelationships between physical chemistry and biology, catalyzed by circumventing the second law of thermodynamics. Chapter 11, entitled “Vertical integration of cytoskeletal function from yeast to human,” examines the roles of the mechanical “superstructure,” the cytoskeleton and skeleton, as organizing principles for integrated physiology as an existing form that relates all the way back to the origins of life itself. In Chapter 12, entitled “Yet another bite of the ‘evolutionary’ apple,” we go through the reverse logic of physiology emanating from the unicellular state. It may seem redundant, but because of the counterintuitive nature of the approach it is helpful to see this viewpoint in multiple ways. Chapter 13, entitled “On eliminating the subjectivity from biology: predictions,” addresses the value added in seeing physiology and evolution from their origins. Chapter 14, entitled “The predictive value of the cellular approach to evolution,” recapitulates the concept that by starting from the cellular origins of life the underlying principles of seemingly complex, indecipherable physiologic principles can be understood and expanded to all of physiology. Chapter 15, entitled “Homeostasis as the mechanism of evolution,” provides a mechanistic integration for the how and why of evolution. Beginning with the protocell, homeostasis acts as the integrating principle on a scale‐free basis. Chapter 16, entitled “On the evolution of development,” takes the dogma of development and shows how it becomes part of the continuum of evolution using the principles provided in the previous chapters. Chapter 17, entitled “A central theory of biology,” provides the first comprehensive perspective on the “first principles of biology.” By utilizing the unique view provided by cell biology as the common denominator for ontogeny and phylogeny, biology can be seen as having a logic. Chapter 18, entitled “Implications of evolutionary physiology for astrobiology,” demonstrates how the principles of physiology and evolution on Earth can provide a logical way of thinking about extraterrestrial life. Chapter 19, entitled “Pleiotropy reveals the mechanism for evolutionary novelty,” provides a way of thinking about how the return to the unicellular state during the life cycle offers the opportunity for the reallocation of genes to generate novel physiologic traits. Chapter 20, entitled “Meta‐Darwinism,” provides examples of the power of the cellular‐molecular approach to evolution.

The content of this book constitutes a novel, mechanistic, testable, refutable approach to the questions of ‘how and why’ evolution has occurred. This book is dedicated to that sea change.

John S. TordayVirender K. Rehan

1Introduction

There are these two young fish swimming along, and they happen to meet an older fish swimming the other way, who nods at them and says, “Morning, boys. How's the water?” And the two young fish swim on for a bit, and then eventually one of them looks over at the other and goes "What the hell is water?"

David Foster Wallace, Kenyon College Commencement Speech, 2005

The premise of this book is that the Big Bang of the Universe gave rise to inorganic and organic compounds alike. Both are formed by bonds, the former constituted by inertness, the latter doing quite the opposite by giving rise to life itself. Organic chemistry provided the physical space within which negentropy, chemiosmosis, and homeostasis all acted in concert to form the first primitive cells. Single‐celled organisms dominated the Earth for the first 3 or 4 billion years, followed by the generation of multicellular organisms as exaptations. How and why this occurred provides the mechanism for the emergence of human biology, starting with the “first principles of physiology.” Such a rendering is way overdue, since the human genome was published more than a decade and a half ago. Without such an effectively predictive working model for physiology, such information is of little value.

Mind the Gap

Let us go then, you and I,

When the evening is spread out against the sky

Like a patient etherized upon a table…

T.S. Eliot, The Love Song of J. Alfred Prufrock

The Michelson–Morley experiment (1887) refuted the notion of luminiferous aether, a theorized medium for the propagation of light, making way for novel thinking about the fundamental principles of physics at the close of the nineteenth century and the beginning of the twentieth. This second scientific revolution was crowned by Relativity Theory (1905), equating energy and mass, a counterintuitive relationship that changed not only the way we see the world around us, but also how we see ourselves. The understanding of the inner workings of the Bohr atom similarly gave insights to physics and chemistry that were previously inaccessible and inconceivable. The twenty‐first century has been declared the “age of biology,” given our foreknowledge of the genetic makeup of humans and an ever‐increasing number of model organisms. Yet the promise of the human genome – the cure for all of our medical ills – has not transpired 15 years hence. We contend that this is symptomatic of our not having attained the level of knowledge in biology that the physicists had reached at the dawn of the second scientific revolution…we are still mired in the sticky, sludgy, stodgy “aether” of descriptive biology. Deep understanding of the inner workings of the cell, particularly as they have facilitated the evolution of multicellular organisms, will herald such breakthrough science. The way in which the cell acts at the interface between the external physical and internal biological “worlds,” authoring the script for Life, is a reality play without an ending, reiterative and reinventive. Thus life is formulated to continually learn from the ever‐changing environment, making use of such knowledge in order to sustain and perpetuate it.

Duality, Serendipity, and Discovery

The field of biomedical research is characterized by paradoxes, serendipitous observations, and occasional discoveries. This is due to the lack of a central theory of biology, DNA notwithstanding. It is also the reason why we have been unable to solve the challenging “puzzle” of evolution. In lieu of guidelines and principles, we collect anecdotes and make up “Just So” stories based on associations and a posteriori reasoning. This book was written to elucidate how to understand biology based on its origins in unicellular life, evolving in the forward direction of biologic history, both ontogenetically (short‐term history) and phylogenetically (long‐term history). We use the figure‐ground image (Figure 1.1), made popular by gestalt psychology, as a way to express the inherent problem in seeing biologic phenomena as dualities: inorganic‐organic, genotype‐phenotype, proximate‐ultimate, structure‐function, health‐disease, synchronic‐diachronic, ontogeny‐phylogeny. It is the latter duality that was the breakthrough for us, realizing that ontogeny and phylogeny, looked at from a cellular perspective, are actually one and the same process, only seen from different perspectives. With that issue put behind us, we could address the “first principles of physiology,” beginning with the plasmalemma of protists as the homolog for all of the subsequent traits expressed by multicellular organisms.

Figure 1.1 Figure‐ground “faces.”

Biology as “Stamp Collecting”

As working scientists, the authors of this book have been involved in studies of developmental physiology for many decades. One of us (J.T.) was first introduced to the concepts of cell biology in reading Paul Weiss, one of the founders of the discipline, when he took advanced placement biology in high school. It was Weiss who admonished us not to ask “how or why” questions, but merely to describe biologic phenomena. That attitude prevailed in biology until the advent of molecular biology in the 1960s, which demanded that we ask how biologic mechanisms functioned, having finally “reduced” the problem to its smallest functional unit, the cell, like the Bohr atom in physics. Yet this reductionist approach has not solved some of the remaining fundamentals of physics, hence string theory, “branes,” and multiverses. By analogy, we are of the opinion that we must think in terms of the cell as the smallest functional unit of biology. Conversely, stripping away billions of years of biologic information to focus on DNA is a systematic error that is misleading and misguided, in our opinion. This book is intended to demonstrate how the cell‐molecular approach to evolutionary biology provides novel insights to the how and why for the evolution of form and function.

The “why” question has emerged from the New Synthesis of evolutionary biology, particularly after it had embraced developmental biology as evo‐devo. But even at that, the evolutionists were not delving into the mechanisms of evolution, seemingly content with random mutation and population selection as the mechanisms of evolution. For working scientists like ourselves, studying how organs develop across species, this didn’t seem like a reasonable process since we could see the common denominator between ontogeny and phylogeny at the cellular level, suggesting (to us) that some underlying organizing principle was at large. Not to mention that the ongoing serendipitous, anecdotal nature of both biology and medicine, even in the post‐Human Genome Project era, was frustrating given that science is ultimately supposed to be predictive.

Then in 2004 Nicole King published her ground‐breaking paper demonstrating for the first time that the complete multicellular genomic “toolkit” of sponges was expressed in the unicellular free‐swimming amoeboid form during the life cycle. That reversed everything in biology because up until that point in time physiology was described based on biologic traits in their extant form, not based on how they evolved from the unicellular state. That perspective precipitated our hypothesis that the complete phenotypic toolkit was present in the plasmalemma of unicellular organisms, and raised the question as to how the genome determined complex physiology ontogenetically and phylogenetically, from unicellular organisms to invertebrates and vertebrates.

That question was made all the more pertinent because we had published a seminal paper on the cell‐molecular basis of alveolar physiology that had emerged from decades‐long study of how the fetal lung develops at the cell‐molecular level. Those studies were catalyzed by two landmark observations – the physiologic acceleration of lung development by glucocorticoids, and the observation that parathyroid hormone‐related protein (PTHrP) was necessary for alveolar formation. The linking of those two phenomena through the serial paracrine interactions between the lung endoderm and mesoderm culminated in our fundamental understanding of the physiologic principle of ventilation‐perfusion matching – essentially how the distension of the alveolar wall molecularly coordinated surfactant production and alveolar capillary perfusion to maintain both local and systemic homeostasis.

The experimental evidence for the coordinating effects of cell stretching on PTHrP, leptin, and their cognate cell‐surface receptors on surfactant production and vascular perfusion led to the first scientific documentation of the physiologic continuum from development to homeostasis. More importantly, it begged the question as to how these specific cell types evolved the mammalian lung phenotype, given that the molecular ligand and receptor intermediates involved were highly conserved, deep homologies that could be traced at least as far back as the origins of vertebrate phylogeny in fish, if not all the way back to the unicellular state. If that “story” could be told, it would provide insight to both lung physiology and pathophysiology based on first principles – a counterintuitive idea predicted by this cell‐molecular approach.

More importantly, the functional genomic linkage between lung evolution in complex climax organisms – mammals and birds – and homologous mechanisms in emerging unicellular eukaryotes, formed the basis for fundamental insights into the evolution of all visceral organs. The advent of cholesterol, which Konrad Bloch referred to as a “molecular fossil,” was critical for the evolution of eukaryotes from prokaryotes. The insertion of cholesterol into the cell membrane of eukaryotes enabled vertebrate evolution by facilitating endocytosis (cell eating), increased gas exchange (due to the thinning of the eukaryotic cell membrane), and increased locomotion (due to increased cytoplasmic streaming). And vertebrate evolution is founded on those three biologic traits – metabolism, respiration, and locomotion. Therefore, all of the visceral organs – lung, kidney, skin, skeleton, brain, and so forth – likely evolved from the plasmalemmae of unicellular organisms, providing a unified, common homolog for all of these organs. The existence of vertebrate physiologic mechanisms based on functional cell‐molecular homologies, rather than on the tautologic “Just So” stories for physiologic structure and function that currently prevail, would no longer hamper forward progress in understanding the “how” and “why” of biology and medicine.

Up until now, the void between descriptive and mechanistic physiology has been filled by either top‐down descriptive physiology, or bottom‐up abstract philosophy and mathematics. With the insights gained from the “middle‐out” ligand‐receptor approach we have employed to understand lung evolution, we are now enabled for a paradigm shift from post‐dictive to predictive physiology and medicine.

Historically, physicists became actively involved in biology after the Second World War as an alternative source of employment, having successfully developed and deployed the atomic bomb. The Greek philosophers understood the unity of life intellectually as far back in written history as the fifth century BCE, but had no scientific evidence for it. Beginning with quantum mechanics, physicists felt empowered to comment on the meaning of life, given that they had discovered the operating principle behind the atom and had unleashed its power. Bohr was the first modern physicist to address the question of “what is life” by applying the conceptual principle of the duality of light to biology in his Como lecture in 1927. He went on to explain that this seeming duality was a technical glitch due to the different ways in which the wave and packet forms of light were measured, a phenomenon he referred to as complementarity. This was a metaphor that poets such as Robert Frost (in his poem The Secret Sits) have reconciled more facilely, in our opinion:

We dance round in a ring and suppose,

But the Secret sits in the middle and knows.

Or for that matter, the glib comment in Robert Frost’s published notebook: “Life is that which can mix oil and water.” Erwin Schrödinger later wrote a monograph, entitled What is Life?, in which he tried to apply physical principles to the question of the vital force. Others followed, such as the Nobelist Ilya Prigogine, and the polymath Michael Polanyi, who expressed their considered opinions that biology was “irreducible.” More recently, in his Nobel Prize acceptance speech, Sydney Brenner stated that the problem of biology is soluble, citing his CELL project to map all of its intracellular pathways. Of course, the greatest of all physicists, Albert Einstein, kept the problem of “life” at arm’s length, yet it was his intuitive insight that led him to E = mc2, transcending the stigma of descriptive physics by equating mass and energy. He had already seen the “forest for the trees” at 16 years of age, dreaming that he was traveling in tandem with a light beam (see Einstein by Walter Isaacson). Like scientific feng shui, he was able to conceive of the fundamentals of the physical world – Brownian movement, the photoelectric effect, and relativity theory – all in his wunderjahr of 1905. Of course, he famously said that “G_d does not play dice with the Universe,” so he would not have agreed with the conventional stochastic approach to evolution.

But perhaps the solution to the evolution puzzle is not based on random mutation and population selection – biology and medicine are on the threshold of a conceptual breakthrough on a par with such breakthroughs as heliocentrism and relativity theory. By subordinating descriptive biology to cell‐molecular signaling in development, homeostasis, and regeneration as the essence of evolution, the fundamental mechanism of life, we will be able to understand the “Inner Universe” of physiology, starting from its origins, resynthesizing biology from the bottom up. Embracing this approach to physiology would be a game changer.