Oxygen

by Nick Lane

  At lower levels of oxygen (40 or 50 per cent oxygen, or about twice our normal exposure), the lungs can normally withstand injury and continue to function, though they may become damaged in the end. In these circumstances, the rest of the body adapts by slowing down the heart beat and producing fewer red blood cells. These adaptations are the opposite of the changes that take place to oxygen deprivation at high altitudes. The result, in both cases, is that the tissues receive the same amount of oxygen as before, no more nor less. Such adaptations illustrate the importance of unchanging oxygen levels in the body. They also mean that we cannot gain any long-term benefit from either high or low levels of oxygen, except when we are sick and pathologically oxygen-deprived.5

  I imagine that most people are comfortable with the idea that too much oxygen can be bad — in effect, that it is possible to have too much of a good thing. Similarly, there is nothing challenging about the idea that we respond to moderate perturbations by re-establishing the physiological status quo. It is a very different proposition to say that 21 per cent oxygen is toxic and will kill us in the end. This is as much as to say that, despite millions of years of evolution, we still cannot adapt to the concentration of oxygen that nature has provided for us. This statement is counter-intuitive to say the least, yet it is the basis of the so-called ‘free radical’ theory of ageing. In essence, this theory argues that ageing, and so death, is caused by breathing oxygen over a lifetime. Oxygen is thus not only necessary for life, but is also the primary cause of ageing and death.

  5 Athletes training at altitude must come down to sea level and race within days or weeks or else the benefits are lost. When we train at altitude, we generate more red blood cells to absorb extra oxygen from the thin air. When we return to sea level, we adapt back to the higher levels of oxygen by producing fewer red blood cells. The benefits never outlast the adaptation.

  12 • INTRODUCTION

  Many people have heard of free radicals, even if they have only a hazy idea of what they actually are. Most free radicals of biological importance are simply reactive forms of molecular oxygen, which can damage biological molecules (we will consider them in detail in Chapter 6).

  Regardless of whether oxygen causes convulsions and sudden death, or slow lung damage, or ultra-slow ageing, it always acts in exactly the same way: all forms of oxygen toxicity are caused by the formation of free radicals from oxygen. As the great sixteenth-century alchemist Paracelsus said, the poison is in the dose. Convulsions are caused by a massive excess of free radicals acting on the brain, lung damage by a smaller excess acting on the lungs. But free radicals are not just toxic. Fire is impossible without free radicals. So too is photosynthesis or respiration. When we use oxygen to extract energy from food we have to produce free-radical intermediates. The secret to all the chemistry of oxygen, whether we think of it as

  ‘good’ or ‘bad’, is the formation of free radicals.

  As conventionally stated, the idea that breathing oxygen causes ageing is disarmingly simple. We produce free radicals continuously inside every cell of our body as the cells respire. Most of these are ‘mopped up’

  by antioxidant defences, which neutralize their effects. The trouble is that our defences are not perfect. A proportion of free radicals slip through the net and these can damage vital components of cells and tissues, such as DNA and proteins. Over a lifetime, the damage gradually accumulates until it finally overwhelms the ability of the body to maintain its integrity.

  This gradual deterioration is known as ageing.

  According to this conventional, if simplistic, explanation, the more antioxidants we eat, the more we can protect ourselves against damage from free radicals. This is why fruit and vegetables are good for us: they contain lots of antioxidants. Nowadays, many people supplement their diet with potent antioxidants in the belief that their diet cannot provide an adequate supply. The implication is that if we eat enough of the right kind of antioxidants, we can postpone ageing and the diseases of old age indefinitely. This has been touted as ‘the antioxidant miracle’.

  The truth is rather more complicated, but far more interesting. I shall argue that oxygen free radicals do cause ageing, but that the implications are almost exactly the opposite of what we might expect. We will never extend our lives significantly, to 150 or 200, by loading ourselves with even the most potent antioxidant supplements. On the contrary, antioxidant supplements might actually make us more vulnerable to some diseases. Antioxidants are bit players in the large cast of adaptations that

  Elixir of Life — and Death • 13

  life has made to the presence of oxygen in the air. We can only understand their role if we consider them in the context of the play as a whole.

  The response of life to the threats and the possibilities of oxygen include adaptations that have had the most profound consequences.

  Let’s just consider a few examples. Take photosynthesis — the formation of organic matter by plants, algae and some bacteria using the energy of sunlight — which today supports almost all life on Earth. It is probable that photosynthesis (which generates oxygen as a waste product) could only have evolved because life had already adapted to provide itself with defences against the oxygen free radicals produced by ultraviolet radiation in the environment. This may explain why life took off on Earth but never did on Mars. Take the abundance of large animals and plants characteristic of our world. The first multicellular organisms probably evolved from clumps of cells which clustered together to deal collectively with the rising tide of atmospheric oxygen produced by photosynthesis.

  Without the threat of oxygen toxicity, life would never have advanced beyond a green slime. Even gigantism relates to oxygen. Giant size offers an escape from the threat of oxygen, as metabolic rate is slower in very large animals, and explains the evolution of monster dragonflies, with a wingspan as broad as a seagull, and possibly the rise and fall of the dinosaurs. Think about the sexes. Why should there be only two sexes?

  Why not one, or three, or many? The evolution of two sexes may have been a way of coping with oxygen. We shall see that babies can only be born young if they are born of two sexes, otherwise oxygen causes the birth of degenerate offspring, destined to age prematurely. This may explain why cloned animals tend to die young. Dolly the sheep, for example, already has arthritis at the age of five, betraying a ‘real’ age of eleven. Finally, think of powered flight. Birds and bats have exceptionally long lives for their sizes. Why? Flying demands metabolic adaptations to oxygen that also confer a long lifespan. If we want to extend our own lifespan, we must look to the birds.

  These are grand statements, which I shall explain and defend later in the book. They are all part of our journey to find out how oxygen affects our own lives and deaths.

  This is unashamedly a book about science. It is not a catalogue of dry facts about how the world works; rather, like science itself, it is full of quirks,

  14 • INTRODUCTION

  experiments, oddities, speculations, hypotheses and predictions. Science is often presented as ‘the facts’, frequently in short sound-bites. The scientific method is described as a methodical unravelling of ‘the truth’, which, if this were true, would bore most people, including most scientists, to tears. The impression that science gives access to an objective reality (as opposed to the subjective world of ethics) sets it up in opposition to religion as an ethical system and gives scientists an air of preaching. In fact, science gives vivid insights into the workings of nature, but falls short of objective reality. Too often, scientific ‘facts’ turn out to be wrong or misleading — we are told that there is ‘no risk’ of a Frankensteinian disaster, only to see it come true before our eyes. At other times, scientists squabble about the meaning of obscure research findings, discrediting their colleagues in public. It is hardly surprising that the general public views science and scientists with growing scepticism. Apart from the unfortunate schism this opens up in society, it means that fewer young people dream of bec
oming scientists. This is a tragedy. I wonder if the tragedy might be averted to some extent if people had a better idea of the workings of science — of the fun, creativity and adventure.

  The real interest of science lies in the unknown, the excitement of charting new terrain. Poking around in the unknown rarely generates a perfect picture of the world — we are more likely to construct a kind of medieval map, a distorted but recognizable picture of reality. Scientists try to link together the contours of a story through experiments that fill in a detail here or there. Much of the joy of science lies in devising and interpreting experiments that test these hypothetical landscapes. I have therefore been careful to explain the experiments and observations that underpin the story of this book. I have tried to show how it is that science can be interpreted in different ways, and I have presented the evidence itself, along with its flaws, so that you may judge for yourself whether my own interpretation is convincing. I hope this approach will help you to share the spirit of adventure along the border of the known and the unknown.

  Science, then, generates hypotheses based on evidence that is specific but limited in scope – islands of knowledge in a sea of unknowing. Very often, individual results only make sense when seen in the context of a bigger picture. All scientific papers have a discussion section, whose purpose is to place the new results in perspective. But science is nowadays highly specialized. It is rare for a medical researcher to refer to the studies of geologists and palaeontologists in the discussion, or for a chemist to be

  Elixir of Life — and Death • 15

  much concerned with evolutionary theory. For most of the time this matters little, but in the case of oxygen, perspective is obliterated by too confined a view. In this case, geology and chemistry have a great deal to say on evolutionary theory, and palaeontology and animal behaviour have much to contribute to medical science. All these fields offer insight into our own lives and deaths.

  If an understanding of oxygen’s role in life and death requires a multidisciplinary approach, it also offers fresh perspectives on each of these fields. Looking at evolution and health through the prism of oxygen solves some long-standing conundrums. I have already mentioned one example: the evolution of two sexes. If we start with the dilemma itself —

  why did two sexes evolve — it is difficult to discriminate between one hypothesis and another. We can’t even eliminate the possibility that things ‘just happened’ that way. Thinking about the role of oxygen in ageing may seem to be irrelevant to this problem, but it actually forces us to conclude that two sexes are necessary for reproduction if a species produces motile sex cells that must search for a mate; and it generates a number of predictions. Thinking about life in this way also explains why we cannot extend our lives just by taking antioxidant supplements, and points us to more realistic ways of postponing ageing and the ailments of old age. Oxygen thus acts as a magnifying glass, enabling us to scrutinize life from some unusual angles. That means that this book is about life, death and oxygen, and not just about oxygen.

  I have tried to write for a wide audience who may have little knowledge of science, and hope to be accessible to anyone prepared to make a little effort. The argument works out over the book as a whole, and you’ll have to read to the end to get the full story! Each chapter, however, tells a story of its own, and I have not assumed much prior knowledge from previous chapters. We shall see that life’s adaptations to oxygen, which began nearly 4 billion (4000 million) years ago, are still written in our innermost constitution. We shall see that radiation poisoning, nuclear reactors, Noah’s flood, photosynthesis, snowball Earths, giant insects, predatory monsters, food, sex, stress and infectious diseases are all linked by oxygen. We shall see that an oxygen-centric view gives striking insights into the nature of ageing, disease and death. We shall see that oxygen, a simple colourless, odourless gas, made the world in which we live, framing our own passage across the stage. We shall see all this by thinking about how and why oxygen has influenced the evolution of life from the very beginning.

  C H A P T E R T W O

  In the Beginning

  The Origins and Importance of Oxygen

  In the beginning there was no oxygen. Four billion years ago, the air probably contained about one part in a million of oxygen. Today, the atmosphere is just less than 21 per cent oxygen, or 208 500 parts per million. However this change might have come about, it is pollution without parallel in the history of life on Earth. We do not think of it as pollution, because for us, oxygen is necessary and life-giving. For the tiny single-celled organisms that lived on the early Earth, however, oxygen was anything but life-giving. It was a poison that could kill, even at trace levels. A lot of oxygen-hating organisms still exist, living in stagnant swamps or beneath the seabed, even in our own guts. Many of these die if exposed to an oxygen level above 0.1 per cent of present atmospheric levels. For their ancestors, who ruled the ancient world, pollution with oxygen must have been calamitous. From dominating the world they shrank back to a reclusive existence at the margins.

  Oxygen-hating organisms are said to be anaerobic — they cannot use oxygen and, in many cases, can only live in its absence. Their problem is that they have nothing to protect them against oxygen poisoning: they possess few, if any, antioxidants. In contrast, most living things today tolerate so much oxygen in the air because they are stuffed full of antioxidants. There is a paradox hidden in this progression. How did modern organisms evolve their antioxidant protection? According to the standard

  The Origins and Importance of Oxygen • 17

  textbook view, antioxidants could not have been present in the first cells that began emitting oxygen as a toxic waste product: how could they have adapted to a gas that had not existed before? Yet if this assumption is true — that antioxidants evolved after the rise in atmospheric oxygen —

  then the huge rise in atmospheric oxygen must have posed a very serious challenge to early life. If oxygen had anything like the effect on the first anaerobic cells that it does on their descendants today, then there ought to have been a mass extinction of anaerobic organisms that would put the fall of the dinosaurs in the shade.

  Why should we care? According to the free-radical theory of ageing discussed in Chapter 1, oxygen toxicity sets limits on our lives. If this is true, the ways in which life has adapted to oxygen over evolutionary time should be revealing. Did the rise in atmospheric oxygen really cause a mass extinction? How did life adapt? If ageing and death are caused by an ultimate failure to adapt, can we learn anything from how the survivors of this putative holocaust coped? Can we somehow ‘do more’ of whatever they did? In the next few chapters, we will attempt to answer some of these questions by charting the response of organisms to changing oxygen levels over the aeons.

  The origins and early history of life have attracted renewed research interest in the past few decades. Some of our most basic ideas about the genesis of life have been turned on their heads. Yet so persuasive and ingrained was the old view that even recent biology textbooks cling to its tenets.

  Many scientists working in other fields seem oblivious to the rewriting of their gospels. The old story is worth recounting here because the role ascribed to oxygen emphasizes its toxicity.

  In the 1920s, J. B. S. Haldane in England and Alexander Oparin in Russia independently began to think about the possible composition of the Earth’s original atmosphere, on the basis of gases known to be present in the atmosphere of Jupiter (which could be detected by their optical spectra). Haldane and Oparin argued that if the Earth condensed from a cloud of gas and dust, along with Jupiter and all the other planets, then the original atmosphere of the Earth ought to have contained a similarly noxious mixture of hydrogen, methane and ammonia. Their ideas stood the test of time, and formed the basis of a famous series of experiments by Stanley Miller and Harold Urey in the United States during the 1950s.

  18 • IN THE BEGINNING

  Miller and Urey passed electric sparks (simulating l
ightning) through a gaseous atmosphere comprising the three Jupiter gases, and collected the end-products. They found a complex mixture of organic compounds, including a high proportion of amino acids (from which all living things make proteins, the building blocks of life). Such reactions, they said, could have turned the early oceans into a thin organic soup containing all the precursors of life. The only other ingredients needed for life to congeal out of this soup were chance and time, both of which seemed to be virtually limitless: the planet is 4.5 billion years old, and the first fossils of large animals date from half a billion years ago. Four billion years should have been long enough.

  The choice of the gases to work with made good practical as well as theoretical sense. Hydrogen, methane and ammonia do not last long in the presence of oxygen and light. The mixture becomes oxidized, and when this happens the yield of organic compounds quickly falls off.

  Chemically speaking, oxidation refers to the removal of electrons from an atom or molecule. The reverse process is called reduction, which involves the addition of electrons.

  Oxidation is named after oxygen, which is good at stripping electrons from molecules; to help you remember, think of oxygen as being caustic or destructive, like a paint-stripper. Oxidation strips off the electron paint, whereas reduction has the blanketing effect of a fresh coat of paint.1 The point is that oxygen can strip organic molecules of electrons, often shredding the molecules, which give up their own electrons as a sacrificial offering, in the process. Today, cells counter this kind of damage with antioxidants, but in the beginning there were no antioxidants. Free oxygen would have been an insurmountable problem, because any organic molecules, or incipient forms of life, would have been shredded if much oxygen was present. The fact that life did start can only mean that oxygen was not present in any abundance.