What Is Life?

by Paul Nurse

  Life cannot exist without genes: each new generation of cells and organisms must inherit the genetic instructions they need to grow, function and reproduce. This means that for living things to persist in the long term, genes must be able replicate themselves very precisely and carefully. Only that way can the DNA sequences be kept constant through multiple cell divisions, so genes can withstand the ‘test of time’. Cells achieve this with impressive exactitude. We see the result of this all around us. The DNA sequence of the huge majority of the 22,000 genes that control your cells is almost completely identical to those of all other people on this planet today. They are also largely indistinguishable from those of our ancestors who hunted, gathered and swapped stories around campfires in the depths of pre-history, tens of thousands of years ago. Altogether, the mutations that differentiate your inborn characteristics from mine, and both of us from our prehistoric ancestors, add up to a tiny fraction – less than one per cent – of your total complement of DNA code. This is one of the big discoveries of twenty-first century genetics: our genomes, each three billion DNA ‘letters’ long, are very similar, across genders, ethnicities, religions and social classes. This is an important equalizing fact that societies across the world should appreciate.

  We cannot disregard those scattered variations that we all carry in our genes, however. Although in the small minority overall, they can have a big effect on our individual biology and life history. Some of these variants are shared between me and my daughters and grandchildren, and they explain some aspects of our resemblance as a family. Other gene variants are unique to each of us, and are part of what makes us into distinct individuals, by influencing our physical appearance, our health and our ways of thinking, in either subtle or not so subtle ways.

  Genetics is central to all our lives, shaping our sense of identity and outlook on the world. Late in my life, I discovered something rather surprising about my own genetics. I grew up in a working-class family; my father worked in a factory and my mother was a cleaner. My brothers and sister all left school when they were fifteen, so I was the only one who stayed on at school and, later, went on to university. I had a happy and well-supported, if somewhat old-fashioned, childhood. My parents were rather older than those of my friends, and I used to quip that it was like being brought up by my grandparents.

  Many years later I applied for a ‘Green Card’ so I could take up residence in the USA and start my new job as President of the Rockefeller University, in New York. To my surprise, my application was rejected. The US Department of Homeland Security said it was because the version of the birth certificate I had used all my life did not list the names of my parents. Irritated, I wrote off for the full version of my birth certificate. The shock came when I opened the envelope containing that new certificate. What it showed was that my parents were not my parents – they really were my grandparents. My mother was actually my sister. It turned out that she had got pregnant at seventeen and, since illegitimacy was considered rather shameful at that time, she had been sent to her aunt’s home in Norwich, which is where I was born. When we returned to London, my grandmother, wanting to protect her daughter, pretended to be my mother, and brought me up. The great irony on discovering all this was that although I am a geneticist, I did not know my own genetics! In fact, because everyone who might have known has since died, I still don’t know who my father is: there is just a dash on my birth certificate where his name should be.

  All individuals are born with a relatively small number of novel genetic variants that tend to arise at random and are not shared with either of their biological parents. As well as contributing to what makes individual organisms unique, these heritable differences also explain why living species are not static and unchanging over long periods of time. Life is constantly experimenting, innovating and adapting as it changes the world and the world changes around it. For this to be possible, genes must balance the need to preserve information by staying constant, with the simultaneous ability to change, sometimes substantially so. The next idea shows us how that this can come about and, as a result, how life became so bewilderingly diverse.

  That idea is evolution by natural selection.

  3. EVOLUTION BY NATURAL SELECTION

  Chance and Necessity

  The world is teeming with an extraordinary diversity of life forms. The yellow butterfly that started this book was a brimstone, an early harbinger of spring. With its delicate yellow wings, it is a beautiful example of the amazingly diverse group of animals that we call insects.

  I like insects, particularly beetles, which were a hobby of mine when I was a teenager. There is an astonishing variety of beetles – some scientists think there are over one million distinct species of them throughout the world. Growing up in England, I marvelled at armour-plated ground beetles scurrying around under stones, beetles that glowed at night, red and black ladybirds eating aphids in the garden, powerful water beetles swimming in ponds and weevils in the flour packet. Beetles present us with a cacophony of diversity; they are a microcosm of the diversity of all life.

  Life in all its different forms can at times seem overwhelming: we share our world with countless animals, birds, fish, insects, plants, fungi and an even longer roster of different microbes, each appearing to be well adapted to their own particular lifestyle and environment. No wonder that for millennia most people thought that all this diversity must have resulted from the efforts of a divine Creator.

  Creation myths abound in most cultures. The Judaeo-Christian myth of Genesis, if read literally, claims life was created within just a few days. The pervasive idea, that individual species had each been fashioned by a Creator, led the twentieth century geneticist J. B. S. Haldane to look at the huge diversity of beetles and quip that whoever God is, ‘He has an inordinate fondness for beetles.’

  During the eighteenth and nineteenth centuries, thinkers began to compare the intricate mechanisms of living things with those of the complex machines being designed and constructed during the Industrial Revolution. These comparisons often reinforced religious beliefs: how could such intricacy have come to be without the input of a supremely intelligent designer?

  One colourful example of this kind of reasoning came from the Reverend William Paley in 1802. He asked you to imagine that you were out walking and found a watch on the path. If you opened the watch and examined its complex mechanism, clearly designed for the purpose of tracking time, it would, he argued, convince you that the watch was made by an intelligent Creator. According to Paley, the same logic must apply to intricate living mechanisms.

  We now know that complex life forms endowed with a sense of purpose can be generated without a designer of any kind, and that is due to natural selection.

  Natural selection is the intensely creative process that has produced us – and the extraordinary diversity of living forms that surrounds us – from the millions of different microbe species to the fearsome jaws of the stag beetle, the 30-metre tentacles of the lion’s mane jellyfish, the fluid-filled traps of the carnivorous pitcher plant and the opposable thumbs of the great apes, including ourselves. Without ever deviating from the laws of science or invoking supernatural phenomena, evolution by natural selection has generated populations of increasingly complex and diverse creatures. Over aeons of time, different species have risen to prominence, their forms changing beyond recognition, as they have explored new possibilities and interacted with different environments and other living creatures. All species – including our own – are in a state of perpetual change, eventually becoming extinct or developing into new species.

  For me this story of life is just as full of wonder as any of the creationist myths. Whereas most of the religious stories present us with creative acts that are familiar, even somewhat mundane, and durations of time that we can readily understand, evolution by natural selection pushes us to imagine something much more at the edge of our comfort zone, but also more magnificent. It is a wholly undirected and incremental process
, but when it is embedded in the inconceivably vast duration of time, what scientists sometimes call ‘deep time’, it becomes the most supremely creative force of all.

  The towering figure in evolution is Charles Darwin, the nineteenth-century naturalist who travelled the world in the tiny Royal Naval ship HMS Beagle, collecting specimens of plants, animals and fossils. Hungrily, Darwin gathered observations that supported the idea of evolution and came up with a beautiful mechanism – natural selection – that explained how it worked. He shared all of this in his 1859 book On the Origin of Species. Of all the great ideas of biology, this is probably the best known, if not always the best understood.

  Darwin was not the first to suggest that life evolved over time. As he notes in On the Origin of Species, Aristotle had argued that body parts of animals might appear or disappear over long periods of time. The late eighteenth-century French scientist Jean-Baptiste Lamarck took this further, arguing that different species were linked together in chains of relatedness. He proposed that species change gradually through the process of adaptation, with their form responding to shifts in the environment and changes in their habits. Famously, he argued that giraffes developed their long necks because, with each generation, they stretched upwards to reach leaves higher up on trees, and somehow, the results of that exertion were passed on to their offspring, who would have slightly longer necks. Lamarck’s ideas are sometimes belittled today because he did not get the details of the process of evolution right, but he deserves great credit for providing one of the first comprehensive accounts of the phenomenon of evolution, if not its cause.

  Lamarck was certainly not alone in speculating about evolution. Even in Charles’s own family, his colourful grandfather, Erasmus Darwin, was another early and enthusiastic supporter of evolution. He had a motto inscribed on his coach which read ‘E conchis omnia’, that is ‘everything from shells’, advertising his belief that all life developed from much simpler ancestors, such as the apparently formless blob of a mollusc inside its shell. However, he had to remove it after the Dean of Lichfield Cathedral accused him of having ‘renounced his Creator’. Erasmus obliged, since he was also a successful doctor and understood that, had he not done so, he would have been in danger of losing his more respectable, and therefore wealthier, patients. He was also considered at the time to be a distinguished poet, expounding his views on evolution in verses from his poem The Temple of Nature:

  ‘First forms minute, unseen by spheric glass

  Move on the mud, or pierce the watery mass;

  These, as successive generations bloom,

  New Powers acquire and larger limbs assume;

  Whence countless groups of vegetation spring

  And breathing realms of fin, and feet, and wing.’

  His reputation as a poet may not have survived, perhaps understandably, but his reputation as a scientist has. However, his lines anticipated aspects of the ideas elaborated by his better-known grandson.

  Charles Darwin was more scientific and systematic in his approach to evolution, and his means of communication were more conventional, confining himself to prose rather than verse. He amassed huge amounts of observational data from the fossil record and his studies of plants and animals, both at home and abroad. He organized it all to provide strong evidence for the view, shared by Lamarck, his grandfather and others, that living organisms do evolve. But Darwin did more than that when he proposed natural selection as a mechanism for evolution. He joined up all the dots and showed the world how evolution could actually work.

  The idea of natural selection is based on the fact that populations of living organisms exhibit variations, and when these variants are caused by genetic changes, they will be inherited from generation to generation. Some of these variants will affect characteristics that make certain individuals more successful in producing offspring. This enhanced reproductive success means that the offspring possessing these variants will make up a greater proportion of the population in the next generation. In the case of the giraffe’s long neck, we can infer that the random appearance and accumulation of variants that subtly altered the skeleton and muscles of the neck allowed some of the giraffe’s ancestors to reach slightly higher branches, eat more leaves and gain more nutrition. Eventually, those that could do so proved more resilient and more capable of producing young giraffes, so the herds of giraffes roaming the savannahs of Africa gradually became dominated by individuals with longer necks. This process is known as natural selection since constraints imposed by all manner of natural factors, such as competition for food or mates or the presence of diseases and parasites, ensure that some individuals fare better and therefore reproduce more than others.

  The same mechanism was put forward independently by the naturalist and collector Alfred Wallace. It’s less widely known that both of them followed speculations about natural selection made earlier in the century, in particular by the Scottish agriculturalist and landowner Patrick Matthew in his 1831 book on naval timber. Nevertheless, Darwin was the first to present the whole idea in a convincing, comprehensive and enduringly compelling way.

  Humans have actually been hijacking the same process for thousands of years, using it to breed organisms possessing particular characteristics. This is called artificial selection, and Darwin actually developed his ideas about natural selection by observing the way pigeon fanciers selected particular individuals to breed to produce a wide range of pigeon varieties. Artificial selection can produce dramatic results. It is how we transformed wild grey wolves into man’s best friend, creating dog breeds that range from the tiny Chihuahua to the towering Great Dane. It’s also how the wild mustard plant gave rise to broccoli, cabbage, cauliflower, kale and kohlrabi. These transformations have taken place over a relatively modest number of generations, giving a glimpse of the great power of the evolutionary process when it is allowed to run its course naturally over millions of years.

  Natural selection leads to survival of the fittest – which, incidentally, is not a term Darwin himself used – and to the elimination of individuals that cannot compete. As a consequence of this process, specific genetic changes accumulate in populations, resulting ultimately in enduring changes to the form and function of living species. It can explain how some beetles developed red-spotted wing cases, whilst others learned to swim, roll balls of dung, or glow in the dark.

  Natural selection is a profound idea, which has significance beyond biology. It has both explanatory power and practical utility in several other disciplines, not least economics and computer science. Today, for example, some aspects of software and some engineered components of machines, such as aircraft, are optimized by algorithms that mimic natural selection.

  These products are evolved, rather than designed in the traditional sense. For evolution by natural selection to take place, living organisms must have three crucial characteristics.

  First, they must be able to reproduce.

  Second, they must have a hereditary system, whereby information defining the characteristics of the organism is copied and inherited during their reproduction.

  Third, the hereditary system must exhibit variability, and this variability must be inherited during the reproductive process. It is this variability that natural selection operates upon. It transforms a slow and randomly generated source of variability into the apparently boundless and constantly changing range of life forms that flourish around us.

  Additionally, for this to work efficiently, living organisms must die. That way, the next generation, potentially containing genetic variants that give them a competitive edge, can replace them.

  The three necessary characteristics emerge directly from the ideas of the cell and the gene. All cells reproduce during the cell cycle and all cells have a hereditary system made up of genes, which are copied and inherited on the chromosomes during mitosis and cell division. Variation is introduced by the appearance of chance mutations that change DNA sequences – like the one that led me to discover the c
dc2 gene – which result from either rare mistakes during the copying of the double helix, or environmental damage to the DNA. Cells repair these mutations, but they are not completely successful. If they were, all individuals of a species would be identical and evolution would stop. This means the error rate itself is subject to natural selection. If that error rate is too high the information stored by the genome will degenerate and become meaningless, and if errors are too rare, the possibility for evolutionary change is reduced. Over the long term, the most successful species will be those that can maintain the right balance between constancy and change.

  In complex eukaryote organisms, further variability is introduced during the process of sexual reproduction, when parts of chromosomes are reshuffled during the cell divisions that produce sex cells (also known as germ cells: sperm cells and egg cells in animals, and pollen and ovules in flowering plants), which are made by the process called meiosis. That is the main reason siblings are genetically different from each other: if their parents’ genes are like a deck of cards, they are each dealt a different genetic ‘hand’.

  Many other organisms introduce variation by exchanging DNA sequences directly, between different individuals. This is common in less complex organisms like bacteria, which can swap genes between one another, but also with more complex organisms. This process is called horizontal gene transfer. It is one of the reasons the genes that make certain bacteria resistant to antibiotics can spread rapidly through whole populations of bacteria, and even from one unrelated species to another. Horizontal gene transfer also makes it harder to trace some lineages back through evolutionary time, since it means that the inheritance of genes can flow from one branch of the tree of life into another.