Creation: How Science Is Reinventing Life Itself

Praise for Creation

Suddenly science is close to understanding the Indian rope trick by which life emerged from non-life four billion years ago. Adam Rutherford has written an engaging account of both the mystery and its impending resolution; he has also provided a fascinating glimpse of the impending birth of a new, synthetic biology.

—Matt Ridley, author of Genome

Rutherford makes his case with contagious enthusiasm. . . . Genuinely amazing biology is in the works, and Rutherford delivers a fascinating overview.

—Kirkus Reviews (starred review)

Engaging . . . May it augur many more top-drawer science books by Rutherford.

—Booklist (starred review)

Prepare to be astounded. There are moments when this book is so gripping it reads like a thriller.

—The Mail on Sunday (UK)

Fascinating . . . The extraordinary science and his argument are worth every reader’s scrutiny.

—The Sunday Telegraph (UK)

Rutherford’s academic background in genetics gives him a firm grasp of the intricacies of biochemistry—and he translates these superbly into clear English.

—Financial Times

About the Author

Adam Rutherford is a science writer and broadcaster. Formerly an editor at Nature, he now presents BBC Radio 4’s flagship weekly program, Inside Science, as well as a host of other documentaries. A geneticist by training, he has a PhD from University College London.

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First published in the United States of America by Current, a member of Penguin Group (USA) Inc., 2013

This paperback edition published 2014

Copyright © 2013 by Adam Rutherford

Penguin supports copyright. Copyright fuels creativity, encourages diverse voices, promotes free speech, and creates a vibrant culture. Thank you for buying an authorized edition of this book and for complying with copyright laws by not reproducing, scanning, or distributing any part of it in any form without permission. You are supporting writers and allowing Penguin to continue to publish books for every reader.

First published in Great Britain in a different format and as

Creation: The Origin of Life / The Future of Life by Penguin Books Ltd.

THE LIBRARY OF CONGRESS HAS CATALOGED THE HARDCOVER EDITION AS FOLLOWS:

Rutherford, Adam, Ph. D.

Creation : how science is reinventing life itself / Adam Rutherford.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-1-101-62262-9

[DNLM: 1. Biogenesis—Popular Works. QH 325]

QH325.R818 2013

576.8’3—dc23 2013013441

While the author has made every effort to provide accurate telephone numbers, Internet addresses, and other contact information at the time of publication, neither the publisher nor the author assumes any responsibility for errors or for changes that occur after publication. Further, publisher does not have any control over and does not assume any responsibility for author or third-party Web sites or their content.

Version_5

For David Rutherford, from whose cells I came

Contents

Praise for Creation

About the Author

Title Page

Copyright

Dedication

Introduction

PART I. THE ORIGIN OF LIFE

CHAPTER 1. Begotten, Not Created

CHAPTER 2. Into One

CHAPTER 3. Hell on Earth

CHAPTER 4. What Is Life?

CHAPTER 5. The Origin of the Code

CHAPTER 6. Genesis

PART II. THE FUTURE OF LIFE

CHAPTER 7. Life, Not as We Know It

CHAPTER 8. Created, Not Begotten

CHAPTER 9. Logic in Life

CHAPTER 10. Remix and Revolution

CHAPTER 11. The Case for Progress

Afterword

Acknowledgments

Annotated Bibliography

Index

Introduction

Imagine you were unlucky enough to get a paper cut opening this book. It’s an annoying but trivial injury, painful but easily mended. Yet the response that this incision triggers is complex, organized, and profound. It’s comparable to the human reaction to a large-scale catastrophe such as a flood or an earthquake. As in those disasters, the first phase is an emergency response.

Everything that occurs in and around your cut happens as a beautiful orchestration of individual living cells. At the precise moment the sharp edge of the paper slices through the outermost surface of your skin, cells embedded throughout your flesh, called nociceptors, spark into action. Via long, stringy nerve fibers that sprout from their surfaces, an electrical signal zaps from your fingertip to cells in the cortex of your brain in a fraction of a second. You perceive pain there, and at the speed of thought your brain fires a message back to groups of muscle cells in your arm, telling them to twitch in a coordinated fashion. The muscle contracts. Your arm recoils. All of this happens within a heartbeat.

The cut will have riven cells from one another in the walls of a blood vessel, a key event in kick-starting the healing process. Opening a capillary causes blood to flood the wound. The scarlet of blood is hemoglobin, the protein molecule that ferries oxygen around your body, and it’s packed into the concave disks of red blood cells shaped like a round mint half-sucked on both sides. Red cells account for just under half of the eleven pounds of blood that the average person carries. Most of the rest is made up of plasma, which is mostly water. But in that plasma, comprising less than 1 percent of blood, are cells that are utterly critical in repairing your wound. These are white blood cells, and their job is to find, fight, and thwart any opportunistic invaders such as bacteria, which immediately start trying to sneak into the body in order to flourish, but in so doing cause you infection.

Meanwhile, the tip of the nerve cell that triggered that pain sends out a signal in the blood that attracts platelet cells. These are the body’s rapid response units, which clump together to form a clot to prevent further blood loss. They also act as emergency beacons, sending out signals to summon dozens of other workers—cells and proteins that protect the wound and initiate the process of rebuilding. Muscular cells in the artery walls spasm in synchronized contraction. Your finger throbs. This twitching restricts blood flow and loss, and helps keep immune cells where the action is. The formation of a clot prevents blood loss and hemorrhage, and marks the first phase of wound healing. Now that the barrier between the inside of your body and the rest of the world is reestablished, the cleanup and restoration can proceed.

After an hour, neutrophils comprise the majority of the cells attending the paper cut. These cells carry detectors on their membranes that pick up the chemical emergency signals pulsing out from ground zero, and move in the direction of the strongest of them. On arrival, neutrophils act as specialist cleaners, enveloping bacteria and vacuuming up debris and detritus, finally killing themselves when their task is complete.

Over the next twenty-four hours, another regiment of cells files into the site; each cell matures into the giant Pac-Man of the immune system, the macrophage (which translates into big eater in Greek). They chomp up the neutrophil carcasses and any other potentially damaging remains they find.

Crucially, the cut itself isn’t simply stuck back together; otherwise we would lose the sensitivity that was there before the injury. Nor is it simply a case of plugging the gap with new skin cells; otherwise we would be lumpy and malformed. Our bodies strive to make repairs as invisible as possible, and to restore the body to its preinjury state. The cut needs to be patched up with new flesh, which is a complex collaboration of cells. And that means the birth of tissue.

As with any reconstruction, the foundations must be laid first. Building-block cells called fibroblasts flood the site of the cut over the next couple of days, reproducing themselves and migrating across the surface of the wound from all directions, extending ruffle-like feelers called pseudopodia—fake feet—as they shuffle along. The march stops when they meet in the middle, forming a layer of foundation for the full reconstruction, and they begin to turn themselves into parts of new blood vessels and new skin tissue. Locked down in position, they produce and ooze collagen to lay down a sort of matrix or scaffold for the rest of the reconstruction project.

Skin, of course, is made of cells, but not just one type. Our skin cells grow, layer by layer, from within, with dead cells sloughing off on the outside in a process of continual renewal. Embedded within this matrix are also a host of other cells, including hair follicles, sweat and oil glands, and the blood vessels that feed the flesh with oxygen and nutrients. All of these types of cells have to be rebuilt into the repair tissue.

A month after you opened this book, the cut is effectively healed. But long after you have forgotten all about it, the cells of your body will continue work on the wound for months, maybe a year, remodeling the site to restore it as well as they can and minimizing any scar. The redness fades as the temporary blood vessels that extended to fuel the repair process retreat, and the temporary collagen matrix that acted as a scaffold for the rebuilding is replaced with a more permanent version. A new piece of living tissue, a new piece of you, has been formed in an act of minor but necessary repair.

The entirety of this reconstruction project has been brought about by thousands of cells working together and producing thousands of new, highly specialized cells that make up tissue: epidermis, glands, veins, and arteries. The fact that we, and all life, can create new living tissue out of cells is the grand idea that unites not only all living things, but every living thing that has ever existed.

There are more living cells on Earth than there are stars in the known universe. Take bacteria: my crude estimate is that there are something like five million trillion trillion (5,000,000,000,000,000,000,000,000,000,000) bacterial cells on Earth. You are probably about fifty trillion human cells, give or take a few tens of trillion depending on your size. On top of all that we are all walking petri dishes. Healthy humans are born sterile, a clean slate of only our own cells. But in a typical adult the total human cell count is outnumbered ten-to-one by the nonhuman cells that we carry in our guts, on our skin, and every surface inside and out, more often than not in the form of bacteria. But there are also bacteria’s cousins: archaea, as well as larger and more complex hitchhikers such as yeast cells, protists, and the occasional parasitic worm. Right now you are probably carrying more than a thousand alien species, most of whom you don’t even notice, many of whom you couldn’t live without. Mostly, these passengers are a fraction of the size of human cells, so by mass we’re still mostly human. At a cellular level, though, we are mostly other things.

These numbers are so large as to be bewildering. But they do reflect that our planet is flooded with life—and that life is only carried by cells. Though the reconstruction project of your healing paper cut is awesomely complex, at the same time it is utterly mundane: a cut, a wince, and within a few days, new skin to patch it up. Similar processes occur billions of times every minute all over our planet. Not just paper cuts and wound healing but also the fundamental processes of all life take place through cells.

As we shall see, every single one of these cells, including the new skin cells on your finger, was born when an existing cell divided in two. And because of that simple fact, the cells in your cut have an ancestry dating back four billion years to the one exception to this rule—the very first cell. When new cells are born to patch up that cut, they are the latest in a chain that leads back, perfectly unbroken, to the very beginning of life on Earth.

How do we know this? What is a cell? How are cells able to perform this or indeed any process? How a cut heals may seem trivial, a biological act, albeit one of sophisticated orchestration, that is performed without thought. But in asking how such a refined process came to be, we will arrive ultimately at the same questions and answers that address the nature, and the origin, of life.

This is a book about those questions and their possible answers: the origins of our lives, the origin of all life, and the origins of new life. And at the heart of them all is our modern understanding of the cell.

Where life comes from is one of a small handful of the most fundamental questions we can ask. It is a question that has preoccupied humanity throughout its existence. Every culture and every religion has a creation myth: from the ancient Egyptians, who had a god sneezing, spitting, and masturbating to create the world, to the comparatively restrained Christian story in the book of Genesis, where life was created ex nihilo—out of nothing—and humans out of mud.

The true story began to reveal itself in a period of less than a hundred years between the middle of the nineteenth and twentieth centuries, with the emergence of the three great ideas in biology. As we will find out, cell theory, Darwin’s theory of evolution by natural selection, and the discovery of the structure of DNA combine neatly to describe how life works. But they also bring us to the brink of cracking the big question itself: how life began.

Key elements of that narrative are elusive, and contemporary scientists are hard at work on filling in the gaps. With more fervor than at any time before, a model of genesis is emerging, using the weight of modern biology to reconstruct the deep past. It is only very recently, with our solid understanding of the genes, proteins, and mechanics of these living chemical processes, that we can seriously question how they came to be in the first place. Modern biology has revealed complexity rather than simplicity, and has shown that intricate networks of chemical reactions drive reproduction, inheritance, sensation, movement, thought, and all of the things that life does. None of this happens for free: energy is required to fuel these actions. The bottom line is that without energy, you are dead. In order to work out how life began, we have to unpick all of these networks. It is here, in the microscopic and, indeed, atomic world of the cell, that we are finding the clues to understand these processes—the ones that keep you, your cells, and every cell alive, as they have for billions of years.

As in contemporary astronomy and physics, the great theories of biology are now being tested with groundbreaking experimentation. Our exploration of the universe led to the big bang theory of the origin of everything, and at the Large Hadron Collider on the Swiss-French border the biggest experiment ever undertaken has been running to re-create the universe in its most embryonic form, billionths of a second after conception. In performing this act, physicists have unveiled the Higgs Boson, a most elemental particle that featured at the beginning of time and has continuously since then. So, too, the best way scientists can understand the pathway to life on Earth is also to try to re-create it. In the next few years, for only the second time in four billion years, a living thing, probably something akin to a cell, will be born in the laboratory without coming from an existing cell.

This act of creation will be a result of the story of biology. The knowledge acquired and the techniques invented in the last two or three centuries—but mostly in the last sixty years—have allowed us to dig into the deep past, but have also led us to invent the future. These two fields are intimately interdependent, a tangled thicket that shows how curiosity enables us to find things out. As we have revealed an ever-greater understanding of the processes at the beginning of evolution, we’ve learned how to profoundly manipulate biology in the present, and vice versa: as we take cells apart and reassemble them synthetically, we learn more about the conditions in which the first cells arose. Just like a mechanic learns how to fix, build, and augment the engine of a car by tinkering with, disassembling, and reassembling its parts, biologists can play with cells once they deconstruct them. The second half of this book explores the modification of life by human agency—at how we are designing, engineering, and building new life-forms for a purpose. It began some thirty odd years ago with what became known as genetic engineering—already a technology that has radically changed farming, disease treatment, medical research, and our understanding of living things. And in the last few years, genetic engineering has evolved and spawned a new field—synthetic biology—with a new approach to living systems that renders them tools.

This is a golden age in biology, and feverish work is occurring all around the world to resolve some fundamental questions. Our journey to this revolutionary point in the earth’s history is the story of biology itself. And that story, too, begins with cells.

PART I

The Origin of Life

CHAPTER 1

Begotten, Not Created

Life is made of cells. For that reason, the vast array of these microscopic, gloopy bags is beyond description. In one single species, us for example, there isn’t an absolute number, but of the fifty trillion or so cells that an adult might have, there are hundreds of types: from astrocytes in the brain to the zymogenic cells of the stomach. Along with that variety comes an assortment of dimensions. The longest cells are neurons in the spine, which stretch all the way to your big toe. If size is important, then you should turn to sex. Among the largest cells in humans are the eggs, just about big enough to see with the naked eye. And the smallest cells are their counterparts, sperm. However, what men lack in size they make up for in numbers: the average adult male can produce ten billion sperm per month, whereas women carry a finite number of eggs, one released every month from alternating ovaries between puberty and menopause. Women are born with all of their eggs already in place—the one that made you was made while your mother was growing inside her mother’s womb, meaning that your first cell began its life inside your grandmother. Other than eggs, almost all cells are invisible to the naked eye, and even with a microscope most look unremarkable: tiny, colorless blobs bound by a fractionally less colorless membrane, generally sitting in a fairly nondescript, dimly lit swill. In labs, when we freeze tissue and slice it into slivers less than one-hundredth of a millimeter thick on glass slides, the cells appear packed together in dense abstract patterns. Or we grow them in broth, where they can be seen free-floating like blurry stars in an off-white sky. We stain cells in hues of pink and purple, and more recently in fluorescent greens and reds, to help visualize their inner workings. But in a live body, most are opaque as jellyfish.

Each type of cell is a highly specialized member of a community, working in unison with others to build a fully functional organism. Every process of our lives is a result of those cells performing their jobs. As you read this sentence, the muscle cells around your eyeball contract and relax to control the movement of your eyes from left to right. If you glance above this page now and look at something in the distance, a ring of muscle cells achieves focus by stretching the clear cells in the lens. You move your eyes effortlessly, but this action requires intricate unconscious coordination. Photons of light pass through your lens and hit the cone and rod photoreceptor cells at the back of your eye, in your retina. There they are harvested and converted into electrical impulses that zoom through neurons, via the optic nerve, up to the brain for processing, perception, and, with luck, understanding. Each movement: every heartbeat, thought, and emotion you’ve ever had; every feeling of love or hatred, boredom, excitement, pain, frustration, or joy; every time you’ve been drunk and then hungover; every bruise, sneeze, itch, or snotty nose; every single thing you’ve ever heard, seen, smelled, or tasted is your cells communicating with one another and the rest of the universe.

Douglas Adams once suggested that Earth was not the most appropriate name for our planet, as most of the surface is not solid dirt and rock, but water. Yet if you really wanted to name our home world after a feature that truly differentiates it from the other thousand or so planets that we have found, it would be Cells. Earth, uniquely as far as we know, is bursting with life, and every living thing on our planet is made of cells. Bearing in mind that nine out of ten things that have ever lived on Earth are already extinct, the number of cells that have ever existed is utterly incalculable.

This is a very modern understanding. Biology is a young science, at most 350 years old, and only 150 in terms of a fuller, mature view with comprehensive and universal rules. Physics has an older pedigree. By the mid-seventeenth century, scientists had mapped areas of the cosmos with future-proof accuracy. Isaac Newton was drawing up a set of rules that explained why things move the way they do, and why we can stand on Earth and not float away. But what are now known as the life sciences were a long way behind. The reason for this is that the starting point for most scientific advances is to look at things and work out why they are the way they are. Unlike the stars and planets, no one had even seen—or at least identified—a cell before 1673.

At that time, science itself was forming. Gentlemen scientists such as Newton and Robert Hooke had formed the world’s first scientific body, the Royal Society. But the man who first peered into the minuscule world of the cell at the birth of cell biology was not one of the esteemed, bewigged gentlemen of science. The unlikely beginning of the story of biology must be credited to a Dutch linen merchant named Antonie van Leeuwenhoek.

The business of making and selling cloth was inextricably linked to the development of better optical lenses, as merchants checked the density of fibers and therefore the quality of their fabric using magnifying glasses like a watchmaker’s loupe. Van Leeuwenhoek was a skilled and meticulous lens grinder, working in Delft, the capital of Dutch drapery. He specialized in a technique that involved pulling apart a hot glass rod and squashing the ends back to form a ball, but was secretive about this process, as it had made him the greatest microscopist of his day. Van Leeuwenhoek’s lenses were tiny fat drops not much bigger than a peppercorn, and he attached them to handheld contraptions nothing like current microscopes. His were rectangular copper plates, about one inch by two inches, with a hole at one end to hold the rotund glass-bead lens. On one side there was a silver spike to hold the specimen in front of the lens, held by a screw that could be turned for focusing. It was the fatness of Van Leeuwenhoek’s lenses that gave them their superior magnification.

At least, that was his technological advantage. His other key attribute was insatiable curiosity. Van Leeuwenhoek simply liked looking at small things through his lenses. While I hope the paper cut described in the introduction is entirely imagined, Van Leeuwenhoek deliberately invoked exactly the same repair process out of unbridled curiosity. In a letter published in the Royal Society’s official journal Philosophical Transactions in April 1673, Van Leeuwenhoek wrote, "I have divers times endeavored to see and to know, what parts Blood consists of; and at length I have observ’d taking some blood out of my own hand, that it consists of small round globuls [sic]." We think that he was looking at red blood cells, and this appears to be the very first recorded sighting of individual cells.¹

As his microscopy skills improved he began to look at all manner of bodily samples and fluids. He went on to scrape the matter from between his teeth and observed the bacteria that cause plaque. At the tail end of the seventeenth century, Van Leeuwenhoek was becoming something of a celebrity for his exploration of a microscopic kingdom hidden in plain view. King William III of England and other dignitaries visited him to see what he had seen. One discovery, however, was kept private: his own semen, although he attested in his notes that the sample was acquired not by sinfully defiling myself, but as a natural by-product of conjugal coitus. In this act, which it is perhaps best not to dwell on, he saw sperm for what they are: single cells. He also discovered cells in a bead of water from a local lake and saw what we now loosely call protists: single-celled creatures that include algae and self-powered swimmers.

Van Leeuwenhoek was the first person to definitively see individual red blood cells, sperm, bacteria, and free-living single-celled organisms. This last group he gave a cute name, animalcules, and in the 1670s he sent drawings of his discovery to the Royal Society in London. The fellows expressed skepticism, not least because when they asked Robert Hooke, their resident microscope expert, if he could see the same creatures in water from the Thames, he initially saw nothing.

Hooke’s expertise in looking at tiny things was unparalleled, having published a stunning and popular volume a decade earlier, Micrographia: or Some Physiological Descriptions of Minute Bodies made by Magnifying