Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford is a registered trade mark of Oxford University Press in the UK and certain other countries.
Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by license, or under terms agreed with the appropriate reproduction rights organization. Inquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above.
You must not circulate this work in any other form and you must impose this same condition on any acquirer.
Library of Congress Control Number: 2021945899
ISBN 978–0–19–760454–0
DOI: 10.1093/oso/9780197604540.001.0001
Printed by Sheridan Books, Inc., United States of America
To all who believe, as I do, that the true object of science is neither to accumulate knowledge nor to solve practical problems, but to make the world intelligible.
8.
Preface
From birth to death we are immersed in an ocean of life, a cornucopia of living things: not only other humans but also animals, plants, insects, and all manner of crawly creatures. Life is so abundant, ubiquitous, and familiar that we seldom give thought to the nature of living things, and what sets them apart from nonliving ones such as stones, clouds, and running water. The object of this small book is to make the phenomenon of life intelligible to readers who are not biologists by profession. What is life, what makes living things tick, how are they related to the world of physics and chemistry, and how did they come to be as we find them? These are the fundamental questions that define biology, and what we have learned deserves to be part of the mental furniture of anyone who aspires to scientific literacy.
Like other portentous words, “Life” has multiple meanings. In everyday speech it refers almost exclusively to human affairs: we are preoccupied with making a living while also living a good life, and some are obsessed with when life begins. The usage here is entirely different, that of the naturalist. Our subject is the parade of forms that share the quality called Life, those living today as well as those known to us only through fossils. We humans hold a place in these ranks, and not a minor one either, but the show is not primarily about us.
In the latter half of the twentieth century the staid science of biology was transformed from a largely descriptive practice centered on natural history into an intensely experimental pursuit, focused on how living things work at the level of cells and molecules. The project has been spectacularly successful, finding answers to questions that could barely be formulated before the Second World War. The nature and general architecture of cells, the mechanism of heredity, and how energy is captured and harnessed have largely been clarified. Microbes have been fully integrated into the life sciences, and evolution is recognized as the overarching principle that makes sense of the diversity of life. Applications to medicine, industry, agriculture, and warfare increasingly rule our lives. At the same time, the gap keeps widening between “us,” that is, those who speak Science and take its precepts for granted, and the general public, who understand less and less of what we are up to and are
beginning to question our goals and motives. Here, I suspect, is a major cause of the decline in science’s standing in our time. I do not presume to bridge that gulf, but do hope to lay down a few steppingstones.
The torrent of discoveries has cast a flood of light on age-old questions that straddle the line between science and philosophy: What defines the living state, how did mindless matter beget purpose and meaning, and how did life arise from the dust of the cosmos when the world was young? What we have learned underscores how extraordinary living things are. Intricate and complicated, they obey all the laws of chemistry and physics, yet the existence of life could never have been predicted from those laws. Life stands squarely within the material world but at the same time stands apart, flaunting its autonomy, purposeful behavior, and in one instance the capacity to reflect on its own nature. Now that we know most of the basics about the way living things work, we need to integrate all that mass of facts into a comprehensible and coherent framework; in a phrase, to make biology intelligible. The question so what is life? is not one for the laboratory scientist: you can’t get a grant to study that. But it is an inescapable subject for scientists with a philosophical bent, and over the past two decades I have become obsessed with it.
The trouble is that the volume of biological knowledge is now so vast that it overwhelms the capacity, and the will, of anyone who seeks to grasp large chunks of it whole. Increasingly, the mass of particulars obscures their meaning. I therefore intend to set aside as much of the burden of detail as possible, to extract what seem to me the central principles and to highlight the major questions that biologists ask of nature. This unavoidably entails stepping outside the fields in which I can claim technical expertise, and making personal judgments on matters on which scientists disagree. Science is a journey that remains unfinished, a never-ending conversation in pursuit of understanding. My hope is that what I say here will help readers, and even myself, to better grasp the wonderful and perplexing phenomenon of life.
What do we mean by “understanding”? I use this commonplace term in the sense set forth by the Oxford philosopher Mary Midgley: “Understanding anything is finding order in it. . . . It is simply putting [the object] into a class of things meaningful—noting how its parts relate to it as a whole, and how it itself relates to the larger scene around it.”1 I am not here to present an overview of biology (Ernst Mayr has done that, far better than I could), but to examine the framework of ideas that interpret and explain the facts.
I am a mainstream scientist, steeped in a lifetime of research into the workings of microorganisms, but over the years I have acquired my own
glasses through which to view the world. Most of my opinions fall well within the range of conventional thought, with one possible exception. It is fashionable nowadays to minimize the gap between living things and inanimate matter, and to underscore the fact that life is part and parcel of the common physical universe. That statement is assuredly true, but I am even more impressed by the great gulf between things that have life and those that do not. One could say (paraphrasing the geneticist Theodosius Dobzhansky) that nothing in biology makes sense except in the context of chemistry and physics, but everything in biology comes in its own distinctive flavor. Reflection along these lines has engendered an inclination to physiology and complex systems, and a perspective on life drawn from its history. Unlike chemistry and physics which draw on universal laws, biology explores the consequences and ramifications of a singular event, the origin of life. Life as we know it revolves around cells, each of which is an intricate system of myriads of molecules integrated into a unit of form and function. DNA is a database of central importance, but it does not direct cellular operations; those emerge from cell dynamics and are seldom spelled out in the genes. Living things are products, not of design but of the interplay of heredity, variation, and natural selection. Finally, our voluminous knowledge is bracketed by two enduring mysteries: How life began, and how mind arose from matter. I like to describe my attitude as a sort of vitalism, a latter-day or molecular vitalism. Let what I have written here stand as an introduction to an unfashionable point of view.
Acknowledgments
It was my great good fortune to come of age in science at the midpoint of the twentieth century, just as the transformation of biology was gathering speed. Many of the grand masters of molecular, cellular, and evolutionary biology left their mark on my perception of life as a phenomenon of nature, particularly Richard Dawkins, Brian Goodwin, Stephen Jay Gould, Francois Jacob, Lynn Margulis, Ernst Mayr, Peter Mitchell, Jacques Monod, Harold Morowitz, John Maynard Smith, Tracy Sonneborn, Roger Stanier, Gunther Stent, and Carl Woese. I am also much indebted to Ford Doolittle, Nick Lane, William Martin, Nick Money, Denis Noble, Norman Pace, and James Shapiro for conversations and correspondence that made me question what I thought I knew.
Friends and colleagues, some professional scientists and others not, reviewed the manuscript during its gestation: Roy Black, Harold Breen, Stephen Ernst, Donald Heefner, Ronald Merrill, Diana Sheiness, and also three anonymous readers, thank you all. At Oxford University Press I am indebted to my editor, Jeremy Lewis, for letting this book see the light of day; to Bronwyn Geyer, for much help in navigating the shoals of electronic publishing; to Sylvia Canizzaro for meticulous copyediting; and to Saloni Vohra for keeping the project on track despite the pandemic. The diagrams were prepared by Ben Rogers and his team at Vox Illustration.
It’s one thing to be conscious of one’s forerunners and mentors, and quite another to render due credit. In a book that strives especially to be brief there is no place for the nuanced consideration of particulars, nor for the extensive citations that scientific etiquette demands. Instead, I have chosen a sample of the recent literature to acknowledge books and articles directly pertinent to what I have written here, and to provide a portal for further reading. To those who feel, perhaps quite justly, that their contributions have been insufficiently recognized, I offer my apologies and a reminder that it is the way of science for the best of our productions to be absorbed into the common pool of knowledge, while losing their identity—like raindrops falling into a pond. I like to think of this book as summing up a lifetime’s engagement with science, and one last opportunity to pay tribute to some of those who molded
my understanding of life and the universe. One that comes to mind is a craggy Australian in a bush-hat, seated on a log by the side of a trail in the Tidbinbilla Nature Reserve near Canberra. He asked where we had been, and when I told him he said, “You have been walking too fast to look at anything.” Thanks, cobber—lesson taken.
About the Author
Frank Harold was born in Germany, grew up in the Middle East, and studied science at The City College of New York, the University of California at Berkeley, and the California Institute of Technology. His professional career spans forty years of research and teaching, mostly in Colorado. He is presently Professor Emeritus of biochemistry at Colorado State University and Affiliate Professor of microbiology at the University of Washington. Dr. Harold’s research interests centered on the physiology, energetics, and morphogenesis of microorganisms, and widened to include life and its evolution. He is also a keen traveler, hiker, and lifelong student of history. Now retired, he remains engaged as a writer, lecturer, and philosopher without license.
On Life
PART I
THE NATURE OF LIVING THINGS
1
Strange Objects
One of the fundamental characteristics common to all living beings without exception [is] that of being objects endowed with a purpose or project, which . . . they exhibit in their structure and carry out through their performances.
Jacques Monod, Chance and Necessity1
A Singular State of Matter
Let me begin by stating the obvious: the objects we see all around us fall neatly into two classes, those that are alive and those that are not. Mountains, rocks, clouds, and rivers are “inanimate.” Their forms, transformation over time, and eventual fate are determined entirely by forces from outside the objects themselves. The hulking bulk of Mount Rainier is said to brood over my hometown of Seattle, benevolent in some moods and menacing in others; Native Americans traditionally consider it a god. But we know now that Mount Rainier was sculpted by volcanic ructions, by ice and water, and these—rather than any volition of its own—will shape its future. Animals, plants, even microbes are different, quite strikingly so. Living things drive and guide their own activities, whose only discernible purpose is their persistence and reproduction. Their forms are produced by forces of their own making, and are quite faithfully passed from one generation to the next with the aid of an internal program. Inanimate objects are made, living things make themselves.
At the same time, living things are part of the same world of physics and chemistry that rules the clouds and threw up Mount Rainier. That became abundantly clear when, beginning in the 19th century, chemists began to inquire what living things are made of. It turned out that living things are made of chemical substances, lifeless molecules. Their chief elements are carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur (CHNOPS), with many other elements present in smaller amounts. Every organism is composed of millions, even billions of molecules, of many hundreds of different kinds. Most of these molecules are found in nature only in the context of living things. Yet the laws that govern the structures and interactions of biological molecules are no different from those that produce inorganic minerals, and most biological molecules can nowadays be synthesized in the laboratory. No “vital force” unique to life has ever been found. So life is chemistry, but chemistry of a very special sort. To borrow an evocative phrase from Stuart Kauffman, it seems that life has explored realms of physics and chemistry that inanimate objects never enter. The more I reflect on this, the more impressed I am by the division of the material world into two classes, things that are alive and things that are not.
As a rule, nature dislikes sharp categories; she prefers her boundaries fuzzy. But in the case of life there are very few ambiguous cases, and most of those vanish on closer inspection. True, one candle lights another, but not by reproduction; the size and shape of each flame are determined by its own wax, not by the donor of the light. Crystals grow themselves and supply seeds for another crop of crystals, but again heredity is not involved. Machines make a subtler instance: intricate and purposeful, machines share many features with living organisms, but even the most sophisticated robot cannot make itself. That day may come and then we shall have to think afresh, but for the present all machines are artifacts of life, accessories to the biological universe but not themselves alive. Freeze-dried bacteria are another intriguing case, because many of them revive when placed in a nutritious medium. They were alive once, and may be alive in the future, but they are not alive now. Still, freeze-dried bacteria underscore a crucial principle to which we shall return: the importance of structure. The only objects that do straddle the line between life and nonlife are viruses. Viruses are obligatory parasites that can only multiply after having infected a suitable host. Simple viruses are “mere” chemicals. They form crystals and some can be made by chemists in the laboratory, yet they grow, multiply, and evolve all too quickly. Besides, their chemical makeup (proteins, nucleic acids, sometimes lipids) assures us that
viruses belong to the universe of living things. One can argue that the virion, the virus particle, is not alive, but the consortium of virus and host surely is. Most readers will probably agree that living and nonliving designate distinct classes of objects, but some will not. Spiritually inclined persons often hold that rivers and mountains also have souls, that everything is alive, and that spirit or mind rather than matter is the essence of the universe. I shall not argue the point, which stems from an altogether different usage of the term “living.” Whatever merit there may be in the spiritual take on the world, it seems to miss one of its most remarkable features: that it holds an abundance of those strange objects, material entities that possess “life.”
We Know Life When We See It
Life and living are fiendishly difficult to define,2 but easy enough to recognize. Life is a quality or attribute of objects that draw matter and energy from their surroundings, build and maintain themselves, and reproduce their own kind. It is a prominent phenomenon of nature, just like the tides, earthquakes, and the change of the seasons; not a product of human activities like buildings, nation-states, or poetry. How living things are constructed and how they work are the stuff of modern biology, which we shall sample in what follows. Let me here underscore some aspects that bear directly on the nature of life, and that are necessary elements of biological literacy.
Perhaps the first thing you notice when you begin to explore the universe of living things is its staggering diversity. There are cabbages and there are kings, both living but grossly different. We have towering redwoods, the tiny spiders that live in the crevices of their bark, bacteria and protozoa in the guts of those spiders, and mushrooms all around. What do these have in common, apart from being alive? At first sight nothing at all, but that turns out to be fallacious. When we examine not the forms and workings of the organisms but their chemical makeup, we find a surprising degree of uniformity. All of them are made up of substances of the same kind, such as proteins, nucleic acids, lipids, and a collection of small “metabolites,” substances that occur in nature only in the context of living things. This is not to say that all organisms are chemically the same, far from it; but it clearly indicates that all living things are related, members of a huge extended family. We might have guessed that from the obvious fact that we can eat one another (as Darwin did), but the
unity of biochemistry underscores a fundamental truth: all life on earth is of one singular kind.
A second, subtler general feature of living things is “organized complexity,” visible at every level from chemistry and structure to whole ecosystems. The common term “organisms,” in use since the 18th century, implies both organization and complexity. Scholars continue to bicker over just what is meant by complexity, but it is clearly a function of the number of parts and the ways they interact. An airplane is visibly more complex than a bicycle, which in turn surpasses a wheelbarrow. The number of molecules that make up even the simplest organism staggers the mind. A typical individual bacterium is likely to be a short cylinder, not unlike a propane tank in shape but only 2–3 micrometers long and one micrometer in diameter. Far too small to see with the naked eye, we would have to line up 500 of them end to end to reach the thickness of a dime; it would take a thousand billion to fill a thimble. But this minute speck of life holds some 2 to 3 million protein molecules, of several thousand sorts; 20 million molecules of fatty lipids; and some 300 million small molecules and ions. Let’s not forget water, the most abundant constituent, some 40 billion molecules. All this in just one tiny cell; an amoeba, a thousand times larger by volume than the bacterium, holds correspondingly more molecules.
Complexity of composition is common in nature; a pinch of mud may rival a cell in the number of components. But the complexity of a cell is different; it has purpose (Box 1.1), and that is what the word “organization” conveys. These are very particular molecules, most of which serve a function (colloquially, a purpose) in the operation of the organism and are assembled into a dynamic interactive system. Many are components of minuscule machines that zip together amino acids to make proteins, transport cargo around the cell, or rotate like a propeller to make it move. Almost all the molecules are arranged in space in a particular pattern that is reproduced in every organism of a given kind. Clearly it takes an awful lot of parts, each one in its proper location, to make a whole, a collective, that operates as a unit to persist and reproduce. It is this organized complexity, its nature and origin, that have come to fascinate me.
The first manifestation of organized complexity was recognized in the mid-19th century: all organisms, large and small, are constructed from basic units that came to be called “cells.” Many—in fact, the great majority—are “unicellular”: they consist of a single cell. A minority, which includes all the creatures large enough to see with the unaided eye (animals, plants, fungi)
Box 1.1 Biological Order
Order, organization, function, and purpose are slippery terms, but one can hardly think seriously about life without them. I do not wish to enter into the subtleties of definition, but since they recur throughout this book let me be clear about their usage. Order refers to regularity and predictability. Patterned wallpaper is a classic example, the solar system is another. Cell architecture is highly reproducible from one generation to the next and represents a higher level of order. Organization is a special category of order, defined by the mathematician John von Neumann as order that has purpose. The parts of an airliner are arrayed in an orderly manner to the end that the collective, the “plane,” can fly. Likewise, the molecular parts of a cell are so arranged as to enable the cell as a whole to persist and reproduce. Most of the molecules and structures that make up a cell have functions, in the sense that their loss impairs the performance of the cell as a whole. Gene mutations commonly have that effect. Parts that serve some function can be said to be there for a purpose. The term as used in this book does not imply conscious intent, nor design by any transcendent entity. The only purpose manifest in the existence and operations of cells and organisms is their own persistence and multiplication. If life, or indeed the universe, has any higher purpose it does not leap to the eye.
are “multicellular,” aggregates of numerous cells, millions or billions of them. The human brain alone consists of some 100 billion cells. Each cell is itself an organism, a unit of life that makes and reproduces itself. It is invariably enclosed in a surface structure made up of one or several membranes, that keep the cell’s interior (its “cytoplasm”) separate from the world outside and distinctive in composition and activities. And here is another remarkable feature that should be shouted from the rooftops: cells arise only by reproduction, every cell from a previous cell, and never ever appear de novo out of nonliving matter. Truly, as W. S. Beck said many years ago, “The cell is the microcosm of life for in its origin, nature and continuity resides the entire problem of biology.”3
As microscopes grew sharper and more powerful, they revealed ever more structure and organization within cells. Initially the term “cell” signified little more than a blob of “protoplasm” bounded by a surface (the “plasma membrane”), with a central dot called the kernel, or “nucleus.” By now we
