by Paul Nurse
‘A beautifully written exploration of perhaps the most important question in science. I felt I was being given rare access to a truly deep understanding of a complex and profound subject. This is the best introduction to modern biology I’ve read.’
Brian Cox
‘In this vibrant, lively book, Sir Paul Nurse, discoverer of some of the crucial genes that control the division of cells, takes a deep dive into biology by illuminating five of the essential characteristics of “life”. The writing is so spirited and knowledgeable – and the five sections so full of wondrous revelations – that I could not put it down. This is a book that will inspire a generation of biologists.’
Siddhartha Mukherjee
‘A masterful overview of biology that draws together big ideas, luminous details and personal insights. You emerge with a more profound sense of wonder about the diversity, complexity and interconnectedness of living organisms. It’s the biggest question in biology. And this book represents the best answer I’ve ever seen. Paul Nurse is a rare life-form – a Nobel-winning scientist and a brilliant communicator.’
Alice Roberts
‘Paul Nurse is about as distinguished a scientist as there could be. He is also a great communicator. This book explains, in a way that is both clear and elegant, how the processes of life unfold, and does as much as science can to answer the question posed by the title. It’s also profoundly important, at a time when the world is connected so closely that any new illness can sweep from nation to nation with immense speed, that all of us – including politicians – should be as well-informed as possible. This book provides the sort of clarity and understanding that could save many thousands of lives. I learned a great deal, and I enjoyed the process enormously.’
Philip Pullman
‘Paul Nurse provides a concise, lucid response to an age-old question. His writing is not just informed by long experience, but also wise, visionary and personal. I read the book in one sitting, and felt exhilarated by the end, as though I’d run for miles – from the author’s own garden into the interior of the cell, back in time to humankind’s most distant ancestors, and through the laboratory of a dedicated scientist at work on what he most loves to do.’
Dava Sobel
Life is all around us, abundant and diverse, it is extraordinary. But what does it actually mean to be alive?
Nobel prize-winner Paul Nurse has spent his career revealing how living cells work. In this book, he takes up the challenge of defining life in a way that every reader can understand. It is a shared journey of discovery; step by step he illuminates five great ideas that underpin biology. He traces the roots of his own curiosity and knowledge to reveal how science works, both now and in the past. Using his personal experiences, in and out of the lab, he shares with us the challenges, the lucky breaks, and the thrilling eureka moments of discovery.
To survive the challenges that face the human race today – from climate change, to pandemics, loss of biodiversity and food security – it is vital that we all understand what life is.
To Andy Martynoga (Yog), friend and father
and my grandchildren:
Zoe, Joseph, Owen and Joshua
and their generation
who will need to care for Life on our planet
CONTENTS
Title Page
Dedication
Introduction
1. The Cell
Biology’s Atom
2. The Gene
The Test of Time
3. Evolution by Natural Selection
Chance and Necessity
4. Life as Chemistry
Order from Chaos
5. Life as Information
Working as a Whole
Changing the World
What is Life?
Acknowledgements
About the Author
Copyright
INTRODUCTION
It may have been a butterfly that first started me thinking seriously about biology. It was early spring; I was perhaps twelve or thirteen years old and sitting in the garden when a quivering yellow butterfly flew over the fence. It turned, hovered and briefly settled – just long enough for me to notice the elaborate veins and spots on its wings. Then a shadow disturbed it and it took flight again, disappearing over the opposite fence. That intricate, perfectly formed butterfly made me think. It was both utterly different to me and yet somehow familiar too. Like me, it was so obviously alive: it could move, it could sense, it could respond, it seemed so full of purpose. I found myself wondering: what does it really mean to be alive? In short, what is life?
I have been thinking about this question for much of my life, but finding a satisfactory answer is not easy. Perhaps surprisingly, there is no standard definition of life, although scientists have wrestled with this question across the ages. Even the title of this book, What is Life?, has been shamelessly stolen from a physicist, Erwin Schrödinger, who published an influential book of the same name in 1944. His main focus was on one important aspect of life: how living things maintained such impressive order and uniformity for generation after generation in a universe that is, according to the Second Law of Thermodynamics, constantly moving towards a state of disorder and chaos. Schrödinger quite rightly saw this as a big question, and he believed that understanding inheritance – that is what genes are and how they are passed on faithfully between generations – was key.
In this book I ask the same question – What is life? – but I do not think that only deciphering inheritance will give us a complete answer. Instead I will consider five of biology’s great ideas, using them as steps that we can climb, one at a time, to get a clearer view of how life works. These ideas have mostly been around for some time, and are generally well accepted for explaining how living organisms function. But I will draw these different ideas together in new ways, and use them to develop a set of unifying principles that define life. Hopefully they will help you see the living world through fresh eyes.
I should say, right at the start, that we biologists often shy away from talking about great ideas and grand theories. In this respect we are rather different from physicists. We sometimes give the impression that we are more comfortable immersing ourselves in details, catalogues and descriptions, whether that’s listing all the species in a particular habitat, counting the hairs on a beetle’s leg, or sequencing thousands of genes. Perhaps it is nature’s bewildering, even overwhelming, diversity that makes it seem hard to seek out simple theories and unifying ideas. But important overarching ideas of this kind do exist in biology, and they help us make sense of life in all its complexity.
The five ideas I will explain to you are: ‘The Cell’, ‘The Gene’, ‘Evolution by Natural Selection’, ‘Life as Chemistry’ and ‘Life as Information’. As well as explaining where they came from, why they are important, and how they interact, I want to show you that they are still changing and being further developed today, as scientists all over the world make new discoveries. I also want to give you a taste of what it’s like to be engaged in scientific discovery, so I will introduce you to the scientists who made these advances, some of whom I knew personally. I will also tell you stories of my own experiences of doing research in the laboratory, the ‘lab’, including the hunches, the frustrations, the luck and the rare but wonderful moments of genuinely new insight. My aim is for you to share in the thrill of scientific discovery and to experience the satisfaction that comes through a growing understanding of the natural world.
Human activity is pushing our climate and many of the ecosystems it supports to the edges of – or even beyond – what they can bear. To maintain life as we know it, we are going to need all the insights we can get from studying the living world. That is why in the years and decades ahead, biolog
y will increasingly steer the choices we make about how people live, are born, fed, healed and protected from pandemics. I will describe some of the applications of biological knowledge and the difficult trade-offs, ethical uncertainties and the possible unintended consequences that they can give rise to. But before we can join the growing debates that surround these topics, we first need to ask what life is and how it functions.
We live in a vast and awe-inspiring universe, but the life that thrives right here in our tiny corner of that greater whole is one of its most fascinating and mysterious parts. The five ideas in this book will act like steps that we will move up, progressively revealing principles that define life on Earth. This will also help us think about how life on our planet might have first got started and what life might be like should we ever encounter it elsewhere in the universe. Whatever your starting point – even if you think that you know little or nothing about science – by the time you have finished this book, my goal is for you to have a better sense of how you, me, that delicate yellow butterfly and all other living things on our planet are connected.
It is my hope that, together, we will be closer to understanding what life is.
1. THE CELL
Biology’s Atom
I saw my first cell when I was at school, not long after my encounter with the yellow butterfly. My class had germinated onion seedlings and squashed their roots under a microscope slide to see what they were made from. My inspirational biology teacher, Keith Neal, explained that we would see cells, the basic unit of life. And there they were: neat arrays of box-like cells, all stacked up in orderly columns. How impressive it seemed that the growth and division of those tiny cells were enough to push the roots of an onion down through the soil, to provide the growing plant with water, nutrients and anchorage.
As I learned more about cells, my sense of wonder only grew. Cells come in an incredible variety of shapes and sizes. Most of them are too small to be seen with the naked eye – they are truly minute. Individual cells of a type of parasitic bacteria that can infect the bladder could line up 3,000-abreast across a one-millimetre gap. Other cells are immense. If you had an egg for breakfast, consider the fact that the whole of its yolk is just one single cell. Some cells in our bodies are also huge. There are, for example, individual nerve cells that reach from the base of your spine all the way to the tip of your big toe. That means those cells can each be about a metre long!
Startling as all this diversity is, what is most interesting for me is what all cells have in common. Scientists are always interested in identifying fundamental units, the best example being the atom as the basic unit of matter. Biology’s atom is the cell. Cells are not only the basic structural unit of all living organisms, they are also the basic functional unit of life. What I mean by this is that cells are the smallest entities that have the core characteristics of life. This is the basis of what biologists call cell theory: to the best of our knowledge, everything that is alive on the planet is either a cell or made from a collection of cells. The cell is the simplest thing that can be said, definitively, to be alive.
Cell theory is about a century and a half old, and it has become one of biology’s crucial foundations. Given the importance of this idea for understanding biology, I find it surprising that it has not caught the public imagination more than it has. This might be because most people are taught in school biology classes to think of cells as mere building blocks for more complex beings, when the reality is much more interesting.
The story of the cell begins in 1665 with Robert Hooke, a member of the newly formed Royal Society of London, one of the first science academies in the world. As is so often the case in science, it was a new technology that triggered his discovery. Since most cells are too small to see with the naked eye, their discovery had to wait for the invention of the microscope in the early seventeenth century. Scientists are often a combination of theorist and skilled artisan, and this was certainly true of Hooke, who was equally comfortable exploring the frontiers of physics, architecture or biology as he was inventing scientific instruments. He built his own microscopes, which he then used to explore the strange worlds hidden beyond the reach of the naked eye.
One of the things Hooke looked at was a thin slice of cork. He saw that the cork wood was made up of row after row of walled cavities, very similar to the cells in the onion root tips I saw as a schoolboy 300 years later. Hooke named these cells after the Latin word cella, meaning a small room or cubicle. At that time Hooke did not know that the cells he had drawn were in fact not only the basic component of all plants, but of all life.
Not long after Hooke, the Dutch researcher Anton van Leeuwenhoek made another crucial observation when he discovered single-celled life. He spotted these microscopic organisms swimming in samples of pond water and growing in the plaque he scraped from his teeth: an observation that disturbed him, since he was rather proud of his dental hygiene! He gave these tiny beings an endearing name, that we no longer used today, ‘animalcules’. Those he found flourishing between his teeth were, in fact, the first bacteria ever described. Leeuwenhoek had stumbled across an entire new domain of minute single-celled life forms.
We now know that bacteria and other sorts of microbial cells (‘microbe’ is a general term for all microscopic organisms that can live as single cells) are by far the most numerous life forms on Earth. They inhabit every environment, from the high atmosphere to the depths of the Earth’s crust. Without them, life would come to a standstill. They break down waste, build soils, recycle nutrients and capture from the air the nitrogen that plants and animals need to grow. And when scientists look at our own bodies, they see that for each and every one of our 30 trillion or more human cells, we have at least one microbial cell. You – and every other human being – are not an isolated, individual entity, but a huge and constantly changing colony made up of human and non-human cells. These cells of microscopic bacteria and fungi live on us and in us, affecting how we digest food and fight illnesses.
But before the seventeenth century, nobody had any idea that these invisible cells even existed, let alone that they worked according to the same basic principles as all other more visible life forms.
During the eighteenth century and into the beginning of the nineteenth century, microscopes and microscopic techniques improved, and very soon scientists were identifying cells from all manner of different creatures. Some began to speculate that all plants and animals were built from collections of those animalcules that Leeuwenhoek had identified several generations before them. Then, after a long gestation, the cell theory was finally fully born. In 1839 the botanist Matthias Schleiden and zoologist Theodore Schwann, summarized work from themselves and many other researchers, and wrote ‘we have seen that all organisms are composed of essentially like parts, namely of cells’. Science had reached the illuminating conclusion that the cell is the fundamental structural unit of life.
The implications of this insight deepened further when biologists realized that every cell is a life form in its own right. This idea was captured by the pioneering pathologist Rudolf Virchow, when he wrote in 1858 ‘that every animal appears as a sum of vital units, each of which bears in itself the complete characteristics of life’.
What this means is that all cells are themselves alive. Biologists demonstrate this most vividly when they take cells from the multicellular bodies of animals or plants and keep them alive in glass or plastic vessels, often flat-bottomed vessels called Petri dishes. Some of these cell lines have been growing in laboratories around the world for decades on end. They let researchers study biological processes without needing to deal with the complexity of whole organisms. Cells are active; they can move and respond to the environment, and their contents are always in motion. Compared to a whole organism, like an animal or a plant, a cell may seem simple, but it is definitely alive.
There was, however, an important gap in cell theory, as originally formulated by Schleiden and Schwann. It did not describe how n
ew cells came into being. That gap closed when biologists recognized that cells reproduce by dividing themselves from one cell into two, and concluded that cells are only ever made by the division of a pre-existing cell in two. Virchow popularized this idea with a Latin epigram: ‘Omnis cellula e cellula’, that is, all cells come from cells. This phrase also helped to counter the incorrect idea, still popular amongst some at the time, that life arises spontaneously from inert matter all the time – it does not.
Cell division is the basis of the growth and development of all living organisms. It is the first critical step in the transformation of a single, uniform fertilized egg of an animal into a ball of cells and then, eventually, into a highly complex and organized living being, an embryo. It all begins with a cell dividing and producing two cells which can take on different identities. The entire development of the embryo that then takes place is based on this same process – repeated rounds of cell division, followed by the creation of an ever more elaborately patterned embryo, as cells mature into increasingly specialized tissues and organs. This means that all living organisms, regardless of their size or complexity, emerge from a single cell. I think we would all respect cells a little more if we remembered that every one of us was once a single cell, formed when a sperm and an egg fused at the moment of our conception.
Cell division also explains the apparently miraculous ways the body heals itself. If you were to cut yourself with the edge of this page, it would be localized cell division around the cut that would repair the wound, helping to maintain a healthy body. Cancers, however, are the unfortunate counterpoint to the body’s ability to instigate new rounds of cell division. Cancer is caused by the uncontrolled growth and division of cells that can spread their malignancy, damaging or even killing the body.