What Is Life?

by Paul Nurse

  The global population continues to grow today. As it does, there is increasing concern about the damage human activity does to the living world. Looking ahead, we face the stark combined challenge of eking out yet more food from the land, whilst also trying to reduce our environmental impact. I think we will need to go beyond the methods that drove last century’s agricultural revolution and devise even more efficient and creative ways of producing food.

  But unfortunately, since the 1990s, attempts to create genetically modified (GM) strains of plants and livestock with enhanced properties have often been blocked. Frequently this has had little to do with scientific evidence and understanding. I have seen debates about the safety of GM foods constantly derailed by misunderstanding, misplaced lobbying and the injection of misleading information. Consider the case of golden rice, which has been genetically engineered to incorporate a bacterial gene into one of the rice plant’s chromosomes, which makes it produce large quantities of vitamin A. There are an estimated 250 million preschool children across the world who are deficient in vitamin A, which is a significant cause of blindness and death. Golden rice might provide a direct way to help, yet it has been attacked repeatedly by environmental campaigners and non-governmental organizations (NGOs) who have even vandalized field trials set up specifically to test its safety and its effect on the environment.

  Is it really acceptable to deny the world’s poorest access to inventions that could help their health and food security, especially if that denial is based on fashion and ill-informed opinion rather than sound science? There is nothing intrinsically dangerous or poisonous about foodstuffs made using GM methods. What really matters is that all plants and livestock should be similarly tested for their safety, efficiency and predicted environmental and economic impact, regardless of how they have been made. We need to consider what the science has to say about risks and benefits, uncoloured by either commercial interests of companies, the ideological opinions of NGOs, or the financial concerns of both.

  In the coming decades, I think that we will have to use genetic engineering techniques more. This could be an area where the relatively new branch of science known as synthetic biology could make an impact. Synthetic biologists seek to go beyond the more focused and incremental approaches traditionally used in genetic engineering, to write more radical changes to organisms’ genetic programming.

  The technical challenges here are substantial, and there are questions about how we control and contain these new species, but the potential rewards could be significant. That’s because life’s chemistry is far more adaptable and efficient than most chemical processes people have been able to carry out in labs or factories. With GM and synthetic biology we could reorganize and repurpose life’s chemical brilliance in powerful new ways. It should be possible to use synthetic biology to create nutritionally enhanced crops and livestock, but it could be applied more broadly than that. It could see us creating re-engineered plants, animals and microbes that produce entirely new types of pharmaceuticals, fuels, fabrics and building materials.

  Novel engineered biological systems might even help tackle climate change. The scientific consensus is clear that our planet has entered a phase of accelerating global warming. This is a grave threat to our future and to that of the wider biosphere that we are but one part of. An increasingly urgent challenge is to reduce the amount of greenhouse gases that we emit and reduce the extent of warming. If we could re-engineer plants to carry out photosynthesis even more efficiently than they do, or make it work at an industrial scale, outside the confines of living cells, it might be possible to make biological fuels and industrial feedstocks that are carbon neutral. Scientists may also be able to engineer novel plant varieties that can thrive in marginal environments, for example in degraded soils or areas that are prone to drought, that previously have not supported cultivation. Such plants could be used not only to feed the world but also to draw down and store carbon dioxide to help manage climate change. They could also form the basis of living factories that work in sustainable ways. Instead of relying on fossil fuels, it might be possible to produce biological systems that will feed more effectively off waste, by-products and sunlight.

  In parallel with these engineered life forms, another goal would be to increase the total area of the planet’s surface that is covered by naturally occurring photosynthesizing organisms. This is not such a straightforward proposal as it might first seem. To make a meaningful impact it needs to be implemented at a massive scale, and also there needs to be consideration of the issue of long-term carbon storage once the plants have died or been harvested. It could involve more forests, cultivating algae and seaweed in the oceans, and encouraging the formation of peat bogs. But making any intervention work effectively and quickly enough will stretch our understanding of ecological dynamics to its limits. The ongoing, widespread, and largely unexplained decline in insect numbers is a case in point. Our future is tied to insect species, since they pollinate many of our food crops, build soils, and more besides.

  Progress in all these applications requires better understanding of life and how it works. Biologists of all disciplines – molecular and cellular biologists, geneticists, botanists, zoologists, ecologists and beyond – all need to work alongside one another to help ensure human civilization continues to flourish, together with, rather than at the expense of, the rest of the biosphere. For any of this to succeed we need to face up to the scale of our ignorance. Despite the great progress we have made in understanding how life works, our present understanding is partial, sometimes very much so. If we want to interfere with living systems constructively – and safely – to achieve some of our more ambitious practical goals, we still have much to learn.

  The development of new applications should always move forward hand in hand with efforts to learn more about how life works. As the Nobel prizewinning chemist George Porter once put it: ‘To feed applied science by starving basic science is like economizing on the foundations of a building so that it may be built higher. It is only a matter of time before the whole edifice crumbles.’ But by the same token it is self-indulgent of scientists not to recognize that useful applications should be generated wherever possible. When we see opportunities to use that knowledge for the public good we must do so.

  This creates fresh questions and further problems, however. How do we agree on what we mean by the ‘public good’? If new cancer therapies are hugely expensive, who should get them and who should not? Should advocating vaccine refusal without adequate evidence, or the misuse of antibiotics, be criminal offences? Is punishment for certain criminal behaviours right if they are strongly influenced by an individual’s genes? If germ line gene editing can rid families of Huntingdon’s disease, should they be free to use it? Can cloning an adult human ever be acceptable? And if tackling climate change means seeding the oceans with billions of genetically engineered algae, should it be done?

  These are but a handful of the increasingly urgent and often intensely personal questions that our advancing understanding of life pushes us to ask. The only way to find acceptable answers is through constant, honest and open debate. Scientists have a special role to play in these discussions because it is they who must explain clearly the benefits, risks and dangers of each step forward. But it is society as a whole that must take the lead in the discussions. Political leaders must be fully engaged with these issues. Too few of them today take sufficient notice of the huge impact science and technology have on our lives and economies.

  But the time for politics is after the science not before. The world has seen too often how things can go horribly wrong when the reverse is true. During the Cold War, the Soviet Union was able to build a nuclear bomb and send the first human into space. But work on genetics and crop improvements were severely damaged, because, for ideological reasons, Stalin backed the charlatan Lysenko who rejected Mendelian genetics. People starved as a consequence. More recently, we have witnessed the delays in action brought about b
y climate change deniers, who have ignored or actively undermined scientific understanding. Debates about the public good need to be driven by knowledge, evidence and rational thinking, and not by ideology, unsubstantiated beliefs, greed or political extremes.

  But make no mistake, the value of science itself is not up for debate. The world needs science and the advances it can offer. As self-aware, ingenious and curiosity-driven humans, we have a unique opportunity to use our understanding of life to change the world. It is up to us to do what we can to make life better. Not only for our families and local communities, but also for all the generations to come, and for the ecosystems that we are an inextricable part of. The living world around us not only provides us humans with an endless source of wonder, it also sustains our very existence.

  WHAT IS LIFE?

  This is a big question. The answer I got at school was something like the MRS GREN list, which states that living organisms exhibit Movement, Respiration, Sensitivity, Growth, Reproduction, Excretion and Nutrition. It is a neat summary of the sorts of things that living organisms do, but it is not a satisfying explanation of what life is. I want to take a different approach. Based on the steps we have taken to understand five of biology’s great ideas, I will draw out a set of essential principles that we can use to define life. These principles will then allow us to get deeper insight into how life works, how it got started, and the nature of the relationships that bind together all life on our planet.

  Of course, many others have attempted to answer this question. Erwin Schrödinger emphasized inheritance and information in his prescient 1944 book What is Life? He proposed a ‘code script’ for life, which we now know is written in DNA. But he ended his book by making a suggestion that almost borders on vitalism: he argued that to really explain how life works, we might need a new and as yet undiscovered type of physical law.

  A few years later the radical British-Indian biologist J. B. S. Haldane wrote another book, also called What is Life?, in which he declared, ‘I am not going to answer this question. In fact, I doubt if it will ever be possible to give a full answer.’ He compared the feeling of being alive to the perception of colour, pain or effort, suggesting that ‘we cannot describe them in terms of anything else’. I have sympathy for Haldane’s view, but it does rather remind me of the US Supreme Court Judge Justice Potter, who, in 1964, defined pornography by saying, ‘I know it when I see it.’

  The Nobel prizewinning geneticist Hermann Muller was not so hesitant. In 1966 he offered a ‘stripped down’ definition of a living thing as simply ‘that which possesses the ability to evolve’. Muller correctly identified Darwin’s great idea of evolution by natural selection as core to thinking about what life is. It is a mechanism – in fact, the only mechanism we know of – that can generate diverse, organized, purposeful living entities without invoking a supernatural Creator.

  The ability to evolve through natural selection is the first principle I will use to define life. As shown in the chapter on natural selection, it depends on three essential features. To evolve, living organisms must reproduce, they must have a hereditary system, and that hereditary system must exhibit variability. Any entity that has these features can and will evolve.

  My second principle is that life forms are bounded, physical entities. They are separated from, but in communication with, their environments. This principle is derived from the idea of the cell, the simplest thing that clearly embodies all the signature characteristics of life. This principle invokes a physicality of life, which excludes computer programs and cultural entities from being considered as life forms, even though they can appear to evolve.

  My third principle is that living entities are chemical, physical and informational machines. They construct their own metabolism and use it to maintain themselves, grow and reproduce. These living machines are co-ordinated and regulated by managing information, with the effect that living entities operate as purposeful wholes.

  Together, these three principles define life. Any entity which operates according to all three of them can be deemed to be alive.

  The extraordinary form of chemistry that underpins life needs more elaboration for a full appreciation of how living machines work. A central feature of that chemistry is that it is built around large polymer molecules, formed mainly from linked atoms of carbon. DNA is one of them and its core purpose is to act as a highly reliable long-term store of information. To this end, the DNA helix shields its critical information-containing elements – the nucleotide bases – at the core of the helix, where they are stable and well-protected. So much so that scientists who study ancient DNA have been able to sequence DNA obtained from organisms that lived and died a very long time ago, including DNA from a horse that had been frozen in permafrost for nearly a million years!

  But the information stored in the DNA sequence of the genes cannot remain hidden and inert. It must be transformed into action, to generate the metabolic activities and physical structures that underpin life. The information held in chemically stable and rather uninteresting DNA needs to be translated into chemically active molecules: the proteins.

  Proteins are also carbon-based polymers, but in contrast to DNA, most of the chemically variable parts of proteins are located on the outside of the polymer molecule. This means that they influence the three-dimensional shape of the protein and also interact with the world. This is ultimately what allows them to perform their many functions, building, maintaining and reproducing the chemical machine. And unlike DNA, if proteins are damaged or destroyed, the cell can simply replace them by building a new protein molecule.

  I cannot imagine a more elegant solution: different configurations of linear carbon polymers generate both chemically stable information storage devices and highly diverse chemical activities. I find this aspect of life’s chemistry both utterly simple and completely extraordinary. The way life couples complex polymer chemistry with linear information storage is such a compelling principle that I speculate that it is not only core to life on Earth, but is also likely to be critical for life wherever else it may be found in the universe.

  Though we and all other known life forms depend on carbon polymers, we should not be limited in our thinking about life by our experience of life’s chemistry on Earth. It is possible to imagine life elsewhere in the cosmos that uses carbon in different ways, or life that is not built on carbon at all. The British chemist and molecular biologist Graham Cairns-Smith proposed in the 1960s a primitive life form based on self-replicating particles of crystalline clay, for example.

  Cairns-Smith’s imagined clay particles were based on silicon, a popular choice of science fiction writers when they imagine otherworldly life forms. Like carbon, silicon atoms can make up to four chemical bonds and we know they can form polymers: these are the basis of silicon sealants, adhesives, lubricants and kitchenware. In principle, silicon polymers might be large and varied enough to contain biological information. However, despite silicon being far more abundant on Earth than carbon, life here is based on carbon. That might be because under the conditions found on the surface of our planet silicon does not form chemical bonds with other atoms as readily as carbon does, and it does not therefore produce enough chemical diversity for life. It would be foolish, though, to rule out the possibility that silicon-based life, or for that matter life based on other chemistries altogether, might thrive in different conditions found elsewhere in the universe.

  When thinking about what life is, it is tempting to draw a sharp dividing line between life and non-life. Cells are clearly alive and all organisms made from collections of cells are alive too. But there are other life-like forms that have a more intermediate status.

  Viruses are the prime example. They are chemical entities with a genome, some based on DNA, others on RNA, which contains genes needed to make the protein coat that encapsulates each virus. Viruses can evolve by natural selection, thus passing Muller’s test, but beyond that things are less clear. In particular, viruses cannot,
strictly speaking, reproduce themselves. Instead, the only way they can multiply is by infecting the cells of a living organism and hijacking the metabolism of the infected cells.

  So when you catch a cold, viruses enter the cells that line your nose and use your nose cell’s enzymes and raw materials to reproduce the virus many times. So many viruses are produced, in fact, that the infected cell in your nose ruptures, releasing thousands of cold viruses. These new viruses infect nearby cells and get into your bloodstream to infect cells elsewhere. It is a highly effective strategy for a virus to perpetuate itself, but means that the virus cannot operate separately from the cellular environment of its host. In other words, it is completely dependent on another living entity. You could almost say that viruses cycle between being alive, when chemically active and reproducing in host cells, and not being alive, when existing as chemically inert viruses outside a cell.

  Some biologists conclude that their strict dependence on another living entity means that viruses are not truly alive. But it’s important to remember that almost all other forms of life, including ourselves, are also dependent on other living beings.

  Your familiar body is in fact an ecosystem made up of a mixture of human and non-human cells. Our own 30 trillion or so cells are outnumbered by the cells of diverse communities of bacteria, archaea, fungi and single-celled eukaryotes that live on us and inside us. Many people carry with them larger animals too, including a variety of intestinal worms and the tiny eight-legged mites that live on our skin and lay their eggs in our hair follicles. Many of these intimate, non-human companions depend heavily on our cells and bodies, but we also depend on some of them too. For example, bacteria in our guts produce certain amino acids or vitamins that our cells cannot make for themselves.