What Is Life?

by Paul Nurse

  And we should not forget that every single mouthful of the food we eat is produced by other living organisms. Even many microbes, such as the yeast I study, are completely dependent upon molecules usually made by other living organisms. These include glucose and ammonia for example, that are needed for making carbon- and nitrogen-containing macromolecules.

  Plants appear to be rather more independent. They can draw carbon dioxide out of the air and water from the earth, and use the energy of the sun to synthesize many of the more complex molecules they need, including carbon polymers. But even plants rely on bacteria found in or near their roots that capture nitrogen from the atmosphere. Without them they cannot make the macromolecules of life. In fact, this is something that, so far as we know, no eukaryote can do for itself. That means there is not a single known species of animal, plant or fungus that can generate its own cellular chemistry entirely from scratch.

  So perhaps the most genuinely independent life forms – the only ones with some claim to be fully independent and ‘free-living’ – are some that might at first seem rather primitive. These include the microscopic cyanobacteria, often called blue-green algae, that can both photosynthesize and capture their own nitrogen, and the archaea that get all their energy and chemical raw materials from volcanically active hydrothermal vents deep below the sea. Strikingly, these relatively simple organisms have not only survived for far longer than we have, but they are also more self-reliant than we are.

  The deep interdependency of different life forms is also reflected in the fundamental make-up of our cells. The mitochondria that produce the energy our bodies need were once entirely separate bacteria – ones that had mastered the ability to make ATP. Through some accident of fate that took place around 1.5 billion years ago, some of these bacteria took up residence inside another type of cell. Over time, the host cells became so dependent on the ATP made by their bacterial guests that the mitochondria became a permanent fixture. The cementing of this mutually beneficial relationship probably marked the beginning of the entire eukaryote lineage. With a reliable supply of energy, the cells of eukaryotes were able to become bigger and more complex. This, in turn, precipitated the evolution of today’s exuberant diversity of animals, plants and fungi.

  This all demonstrates that there is a graded spectrum of living organisms that ranges from wholly dependent viruses, through to the much more self-sufficient cyanobacteria, archaea and plants. I would argue that these different forms are all alive. That’s because they are all self-directed physical entities that can evolve by natural selection, although they are also all dependent to varying degrees on other living organisms.

  From this broader perspective on life grows a richer view of the living world. Life on Earth belongs to a single, vastly interconnected ecosystem, which incorporates all living organisms. This fundamental connectedness comes not only from their deep interdependency, but also from the fact that all life is genetically related through its shared evolutionary roots. This perspective of deep relatedness and interconnectedness has long been championed by ecologists. It has its origins in the thinking of the early nineteenth-century explorer and naturalist Alexander von Humboldt, who argued that all life is bound together by a holistic web of connections. Unexpected as it may be, this interconnectivity is core to life, and should give us good reason to pause and think more deeply about the impact human activity has on the rest of the living world.

  The organisms that live on the many branches of life’s shared family tree are astonishingly varied. But that variety is outshone by their far greater and more fundamental similarities. As chemical, physical and informational machines, the basic details of their operations are the same. For example, they use the same small molecule, ATP, as their energy currency; they rely on the same basic relationships between DNA, RNA and protein; and they use ribosomes to make their proteins. Francis Crick argued that the flow of information from DNA to RNA to protein was so fundamental to life that he called it the ‘Central Dogma’ of molecular biology. Some have since pointed out minor exceptions to the rule, but Crick’s key point still stands.

  These deep commonalities in life’s chemical foundations point to a remarkable conclusion: life as it is on Earth today started just once. If different life forms had emerged several times independently, and had survived, it is extremely unlikely that their descendants would all conduct their basic operations in such a similar way.

  If all life is part of the same vast family tree, what kind of seed did that tree grow from? Somehow, somewhere, a very long time ago inanimate and disordered chemicals arranged themselves into more ordered forms that could perpetuate themselves, copy themselves and eventually gain the all-important ability to evolve by natural selection. But how did this story, which is eventually our story too, actually start?

  The Earth was formed a little over 4.5 billion years ago, at the dawn of our solar system. For the first half a billion years or so, the surface of the planet was too hot and unstable to have allowed the emergence of life as we know it. The oldest unambiguously identified fossil organisms yet found lived around 3.5 billion years ago. That gives a window of a few hundred million years for life to get up and running. That’s a longer expanse of time than our minds can readily comprehend, but is rather a small fraction of the total history of life on Earth. For Francis Crick, it seemed too improbable that life could have started here on Earth in the time available. That’s why he suggested that life must have emerged elsewhere in the universe and been delivered here in either a partially or fully formed state. But this rather evades, instead of answers, the crucial question of how life might have started from humbler beginnings. Today, we can give a credible, if presently unverifiable, account of that story.

  The oldest fossils look rather similar to some of today’s bacteria. This indicates that life may already have been quite well established by that point, with membrane-enclosed cells, a hereditary system based on DNA, and a metabolism based on proteins.

  But which came first? Replicating DNA-based genes, protein-based metabolism, or enclosing membranes? In today’s living organisms these systems form a mutually interdependent system that only works properly as a whole. DNA-based genes can only replicate themselves with the assistance of protein enzymes. But protein enzymes can only be built from the instructions held in the DNA. How can you have one without the other? Then there’s the fact that both genes and metabolism rely on the cell’s outer membrane to concentrate the necessary chemicals, capture energy and protect them from the environment. But we know that cells alive today use genes and enzymes to build their sophisticated membranes. It’s hard to imagine how one of this crucial trinity of genes, proteins and membranes could have come about on its own: if you take one element away, the whole system rapidly comes apart.

  The formation of membranes might be the easiest part to account for. We know that the kind of lipid molecules that make up membranes can form via spontaneously occurring chemical reactions that involve substances and conditions thought to have been present on the young Earth. And when scientists put these lipids into water, they do something unexpected: they assemble themselves spontaneously into hollow, membrane-bounded spheres that are about the same size and shape as some bacterial cells.

  With a plausible mechanism for forming membrane-bounded entities, that leaves the question of whether DNA genes or proteins came first. The best solution scientists have yet found for this particular chicken and egg-type problem is to say that neither of them did! Instead, it may have been DNA’s chemical cousin, RNA, that came first.

  Like DNA, RNA molecules can store information. They can also be copied, with errors in that copying process introducing variability. That means RNA can act as a hereditary molecule that can evolve. That’s what RNA-based viruses still do today. The other crucial property of RNA molecules is that they can fold up to form more complicated three-dimensional structures that can function as enzymes. RNA-based enzymes are not nearly as complex or versatile as protein e
nzymes, but they can catalyze certain chemical reactions. Several of the enzymes crucial to the function of today’s ribosomes are made from RNA, for example. If these two properties of RNA were combined, they may have been able to produce RNA molecules that work as both gene and enzyme: a hereditary system and a primitive metabolism in the same package. What this would amount to is a self-sustaining, RNA-based living machine.

  Some researchers think these RNA machines might have first formed within the rocks that surround deep-ocean hydrothermal vents. Tiny pores in the rock may have provided a protected environment, whilst the volcanic activity boiling out of the Earth’s crust would have offered a steady flow of energy and chemical raw materials. In these circumstances, it’s possible that the nucleotides needed to make RNA polymers could be made from scratch, by assembling them from simpler molecules. At first, metal atoms embedded in the rock may have acted as chemical catalysts, allowing reactions to proceed without the aid of biological enzymes. Eventually, after millennia of trial and error, this could have led to the formation of machines made from RNA that were alive, self-maintaining and self-replicating and that, sometime later, could have been incorporated into membrane-bounded entities. That would have been a landmark event in the emergence of life: the appearance of the first true cells.

  The story I have just told you is plausible, but please remember it is also highly speculative. The first life forms left no trace, so it is very difficult to know what was happening at the dawn of life or even what precise state the Earth itself was in more than 3.5 billion years ago.

  Once the first cells had successfully formed, however, it is easier to imagine what happened next. First, the single-celled microbes would have spread through the world, gradually, colonizing sea, land and air. Then, 2 billion years or so later, the larger and more complex – but for a very long time still single-celled – eukaryotes joined them. True multicellular eukaryotic organisms came much later, after another billion years or so had elapsed. That means that multicellular life has been here for about 600 million years, just one sixth of life’s total history. But in that time they’ve given rise to all the largest and most visible living forms that surround us, including towering forests, swarming colonies of ants, huge networks of underground fungi, herds of mammals on the African savannah, and very much more recently, modern humans.

  All of this has happened through the blind and unguided, but highly creative, process of evolution by natural selection. But when considering life’s successes, we should remember that evolutionary change can only happen efficiently when some members of a population fail to survive and reproduce. So although life as a whole has proved itself to be tenacious, long-lasting and highly adaptable, individual life forms tend to have a limited lifespan and a restricted ability to adapt when their environment changes. Which is where natural selection comes into play, killing off the old order and, if more suitable variants exist in a population, making way for the new. It seems that it is only through death that there can be life.

  The ruthless winnowing process of natural selection has created many unexpected things. One of the most extraordinary of these is the human brain. So far as we know, no other living thing shares with us quite the same awareness of its own existence. Our self-conscious minds must have evolved, at least in part, to give us more leeway to adjust our behaviour when our worlds change. Unlike butterflies, and perhaps all other known organisms, we can deliberately choose and reflect upon the purposes that motivate us.

  The brain is based on the same chemistry and physics as all other living systems. Yet somehow, from the same relatively simple molecules and well-understood forces, spring our abilities to think, to debate, to imagine, to create and to suffer. How all this emerges from the wet chemistry of our brains provides us with an extraordinarily challenging set of questions.

  We know that our nervous systems are based on immensely complex interactions between billions of nerve cells (neurons) that make trillions of connections between themselves, called synapses. Together, these unfathomably elaborate and constantly changing networks of interconnected neurons establish signalling pathways that transmit and process rich streams of electrical information.

  As is so often the case in biology, we know most of this from studying simpler ‘model’ organisms, such as worms, flies and mice. We know quite a lot about the ways these nervous systems gather information from their environments through their sense organs. Researchers have done a thorough job of tracking the movement of visual, sound, touch, smell and taste signals through the nervous system, as well as mapping some of the neuronal connections that form memories, generate emotional responses, and create output behaviours, such as flexing muscles.

  This is all important work, but it is only a beginning. We have barely scratched the surface of understanding how the interactions between billions of individual neurons can combine to generate abstract thought, self-consciousness, and our apparent free will. Finding satisfactory answers to these questions will probably occupy the twenty-first century and likely beyond. And I do not think we can rely only on the tools of the traditional natural sciences to get there. We will have to additionally embrace insights from psychology, philosophy and the humanities more generally. Computer science can help too. Today’s most powerful ‘AI’ computer programs are built to mimic, in a highly simplified form, the way life’s neural networks handle information.

  These computer systems perform increasingly impressive data-crunching feats, but display nothing that even vaguely resembles abstract or imaginative thought, self-awareness, or consciousness. Even defining what we mean by these mental qualities is very difficult. Here, a novelist, a poet or an artist can help, by contributing to the basis of creative thoughts, by more clearly describing emotional states, or by interrogating what it really means to be. If we have more of a common language, or at least greater intellectual connection, between the humanities and the sciences to discuss these phenomena, we may be better placed to understand how and why evolution has allowed us to develop as chemical and informational systems that have somehow become aware of their own existence. It will take all our imagination and creativity to understand how imagination and creativity can come about.

  The universe is unimaginably vast. By the laws of probability, it seems very unlikely that across all that time and space life – let alone sentient life – has only ever blossomed once, right here on Earth. Whether or not we will ever meet alien life forms is a different issue. But if we ever do, I am confident they, like us, will be self-sustaining chemical and physical machines, built around information- encoding polymers that have been produced through evolution by natural selection.

  Our planet is the only corner of the universe where we know for certain life exists. The life that we are part of here on Earth is extraordinary. It constantly surprises us but, in spite of its bewildering diversity, scientists are making sense of it, and that understanding makes a fundamental contribution to our culture and our civilization. Our growing understanding of what life is has great potential to improve the lot of humankind. But this knowledge goes even further. Biology shows us that all the living organisms we know of are related and closely interacting. We are bound by a deep connectedness to all other life: to the crawling beetles, infecting bacteria, fermenting yeast, inquisitive mountain gorillas and flitting yellow butterflies that have accompanied us during our journey through this book, as well as to every other member of the biosphere. Together, all these species are life’s great survivors, the latest descendants of a single, immeasurably vast family lineage that stretches back through an unbroken chain of cell divisions into the far reaches of deep time.

  As far as we know, we humans are the only life forms who can see this deep connectivity and reflect on what it might all mean. That gives us a special responsibility for life on this planet, made up as it is by our relatives, some close, some more distant. We need to care about it, we need to care for it. And to do that we need to understand it.

  ACKN
OWLEDGEMENTS

  David and Rosie Fickling, for all their efforts to make this book accessible; and to friends and colleagues in my lab and beyond over the years, for discussions and disagreements about the nature of life. Finally, to Ben Martynoga, for helping me greatly and making this book enjoyable to write.

  About the Author

  Paul Nurse is a geneticist and cell biologist who has worked on how the reproduction of cells is controlled. This process is the basis of growth and development in all living organisms. He is Director of the Francis Crick Institute in London and has served as Chief Executive of Cancer Research UK, President of Rockefeller University and President of the Royal Society. He shared the 2001 Nobel Prize in Physiology or Medicine and has received the Albert Lasker Award and the Royal Society’s Royal and Copley Medals.

  He was knighted in 1999 and received the Légion d’honneur from France in 2003 and the Order of the Rising Sun from Japan in 2018. He served for fifteen years on the Council of Science and Technology, advising the Prime Minister and Cabinet, and is presently a Chief Scientific Advisor for the European Commission and a trustee of the British Museum.

  Paul flies gliders and vintage aeroplanes and has been a qualified bush pilot. He also likes the theatre, classical music, hill-walking, going to museums and art galleries, and running very slowly.

  What is Life? is his first book.

  Copyright

  What is Life? – Understand Biology in Five Steps