Authors: Adam Rutherford
The precise point at which life began is unknown, and almost certainly unknowable. It may be that it began multiple times, maybe during the Hadean, but was wiped out all but once by the sterilizing spray of the Late Heavy Bombardment. One 2009 computer model by scientists in Colorado suggests that even had the Hadean eon sterilized the surface of the Earth, life could have survived at the bottom of the ocean.
The consensus (though not unchallenged) is that the first evidence for living matter dates to around 3.8 billion years ago, coinciding with the end of the Late Heavy Bombardment. These clues come in the form of that vitally important atom, carbon. Cells, defining life as we know it, are not visible in the fossil record at this age, as rocks older than 3.5 billion years tend to have undergone the harsh geological metamorphosis that irretrievably churns up any shadow of living structures. Therefore, we have to look for the chemical signatures of life trapped in rocks. In a formation on the west coast of Greenland, rocks have been found that contain the merest trace of a form of radioactive carbon that has no earthly reason to be there, unless it had been processed by a living organism.
We don't know what that life-form was: only by the presence of that carbon can we infer that an organism that had similar fundamental mechanisms to modern life existed all that time ago. Skip forward four hundred million years and the remnants of life are abundant and much less controversial.
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The best of these comes in the form of stromatolites: foot-wide stone mushrooms that sprout from the shallow seas in Australia and other locations around the world. They are formed when floating mats of solar-powered bacteria trap tiny particles of grit in their slimy mucus, and over millennia this floating scum slowly settles into layered lumps of stone.
Ingredients
Yet that is hundreds of millions of years of evolution after the end of the Late Heavy Bombardment. What we see from then are scant pieces bearing evidence of living things in a colossal jigsaw. We have a picture of Earth, more settled than it had been for hundreds of millions of years, but still violent, with electrical storms, churning land masses, volcanoes chugging out gasses into the atmosphere, and tumultuous seas. This is a contemporary understanding of the early earth, and has helped us formulate experiments and hypotheses for the conditions in which life emerged. However, the first speculations about life's emergence predate our current ones by a century.
In 1871, Darwin wrote a letter to his friend Joseph Hooker contemplating the switch from inanimate chemistry to life. On the second page of this almost unreadable document
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he considers not the origin of species, but the origin of life:
It is often said that all the conditions for the first production of a living organism are now present, which could ever have been present. But if (and oh what a big if) we could conceive in some warm little pond with all sorts of ammonia and phosphoric salts,âlight, heat, electricity &c. present, that a protein compound was chemically formed, ready to undergo still more complex changes, at the present day such matter wd be instantly devoured, or absorbed, which would not have been the case before living creatures were formed.
With this famous “warm little pond” Darwin is prefiguring the concept of primordial soup (
primeval,
meaning “original” or the “earliest time,” and
prebiotic,
meaning “before life,” are also used, largely interchangeably). He lists the ingredients of the soup there, just like a recipe. Though ignorant of our modern picture of the Archaean earth, Darwin had casually meandered into what would become the dominant idea of the origin of life. He was not the only one to take these speculative baby steps. One of his biggest champions was the German zoologist and polymath Ernst Haeckel, an early proponent of the idea that biology and chemistry were continuations on the same spectrum. In 1892, he proposed a process in which “the origin of a most simple organic individual in an inorganic formative fluid, that is, in a fluid which contains the fundamental substances for the composition of the organism dissolved in simple and loose combinations.” Chemists were already dabbling in biological alchemy, not gold from base, but conjuring the molecules of biology from chemistry. In 1828, a German scientist, Friedrich Wöhler, synthesized urea, a key biological molecule and a component of urine, noting in his methods that he had done it “without the use of kidneys, either man or dog.” This contradicted the then-popular concept of vitalism, that life was somehow fundamentally different from nonlife. Wöhler had shown that the molecules of life could be made synthetically.
The idea that the birthplace of the first life was a rich pond of ingredients was formalized in the 1920s when a Russian, Aleksander Oparin, and an Englishman, J. B. S. Haldane, both independently wrote about the emergence of complex biological molecules and life in conditions fueled by an oxygen-depleted atmosphere on the early earth. Haldaneâa truly great scientist who went on to become a central figure in the emergence of evolutionary biology in the twentieth century and a gifted science communicatorâis an important character in this scientific journey, as he first used the phrase “prebiotic soup,” and the idea of soup as the stock of life has bubbled away ever since.
Soup had its greatest moment in 1953, a vintage year for science. Crick and Watson revealed the structure of DNA in April, certainly the scientific achievement of the twentieth century. But at exactly the same time, a young student was building on Haldane's and Oparin's ideas to put together another, similarly iconic experiment. Stanley Miller was a twenty-two-year-old chemist at the University of Chicago, and as part of his PhD he begged his supervisor, Nobel Prize laureate Harold Urey, to let him put together a rather fanciful experiment. He built a set of interconnected glass pipes on an electrified metal grid six and a half feet square. This kit now sits in a dimly lit room in the labs of one of Miller's former students, Jeffrey Bada, now an emeritus professor at the Scripps Institution of Oceanography in San Diego. It looks, not inappropriately, like a 1950s sci-fi experiment, with sparks and bubbling gasses and colored liquids. Miller filled the glass beakers with water, methane, hydrogen, and ammonia, in an attempt to emulate what was believed at the time to be the essential ingredients of the early earth. Moving on to the next stage set by Oparin and Haldane, Miller reasoned that the absence of oxygen in the atmosphere was key to the chemical maelstrom necessary to prompt the emergence of essential biological molecules. Miller put thousands of volts' worth of spark into that pipework, mocking the electrical storms and lightning that thundered from the turbulent Archaean sky.
Harold Urey had the good grace to let him pursue this experiment with the caveat that it would be shut down and he would have to move on to less implausible research if it bore no fruit within a few months. No such time was needed. Within days the mix turned pink, then coffee brown. Miller extracted the rich brew; his analysis of it found the presence of the amino acid glycine and a handful of the other biological amino acids essential for building proteins. He published his results in the journal
Science
, noting in the methods that the conditions were designed to emulate the primitive earth, not to optimize the production of amino acids. Just to consolidate that extraordinary result, there's a sweet coda to this experiment. In 2008, a year after Miller died, Jeffrey Bada rediscovered some of the original samples from this experiment tucked away in the back of a dusty drawer. He then subjected them to twenty-first-century analyses. Even in these fifty-year-old samples, precision inspection revealed not just the few that Miller had seen, but all twenty of the biological amino acids, and five others, too. It seems that under those conditions, the spontaneous production of essential biological ingredients was a trivially straightforward happenstance. Those simple units, it might be thought, would string together into proteins that all life depends on, and with their function the processes of life could begin. Miller had shown that in the tumult of the Archaean earth, the molecules that form the universal workers of living systemsâproteinsâwere simply summoned into existence by the equivalent of a bolt of lightning.
The experiment was so appealing that Miller became an international celebrity. The press was amazed and excited; their reporting exaggerated the results to the point where some claimed that Miller had created life. Naturally, amino acids are not life, though they are essential for it, but their creation was big news. This experiment was seen as a stamp of approval for the idea of primordial soup, cementing its place as part of our culture, and the most tenacious idea in the origin of life. In a location somewhere on the earth, a wet surface or pool or floating pumice was exposed to the gasses of the Archaean atmosphere and a bolt of lightning. It carries a sense of drama: the spark of life injected into a corpse, invigorated from the skiesâthe moment of creation.
But could it have been like this? As we have seen in earlier chapters, the mechanics of life are mesmerizingly complicated. A cell is a hive of densely packed activity receiving input from its environment (whether this environment is as part of an organism or as a single free-living cell). Inside the cell, there is code that encrypts proteins, and those proteins enact the functions of living: feeding, communicating with other cells, and the reproduction of the organism to perpetuate the genes it bears. To see the spontaneous emergence in a test tube of the molecules (or components of those molecules) that perform these vital acts certainly provides credence to the idea that the origin of life is neither mystical nor supernatural. At the beginning of the Archaean, simple chemical ingredients did make the transition from chemistry to biology, and Miller's iconic experiment follows in the direct scientific lineage of Darwin's warm little pond. In that charming speculation the recipe includes “ammonia and phosphoric salts,âlight, heat, electricity &c.,” all of which are plausible components as they relate to some of a typical cell's processes. Miller's experiment tested this idea, basing the ingredients on a better understanding of the conditions of the infant earthâammonia, methane, hydrogen, water, and lightning. In the sixty years since, many experiments have further refined the recipe, or shown similar and more sophisticated spontaneous construction of biological molecules out of a soup of ingredients. It's an attractive idea, and one that has stuck. But there are fundamental outstanding questions that underlie these experiments. Can life emerge by cooking up a chemical soup? Is a spark what it takes to drive a chemical reaction into a biological one? To answer these questions, and to get to the bottom of the origin of life, we must ask a very simple question, one with a deeply elusive answer.
What Is Life?
“I shall not today attempt further to define the kinds of material I understand to be embraced within that shorthand description; and perhaps I could never succeed in intelligibly doing so. But I know it when I see it.”
Justice Potter Stewart, 1964
W
hat is living? A definition of life might seem like the most fundamental bedrock on which a field as expansive as biology is built. You might therefore be alarmed to discover that there is no standard definition. At school, we get taught variations on a checklist for identifying the characteristics of living things:
Schools in the United Kingdom sometimes summarize this as the acronym: MRS. GREN. As a checklist, it works perfectly well for all the living things we see around us: you're probably doing at least five of those things right now.
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The criteria above are all facets of life, and are biochemical by natureâbiology as enacted by chemistry. Movement, for example, can take many forms in living things. You scan these words when a network of specialized proteins contracts inside muscle fibers attached to your eyeballs, pulling and pushing the focus across the sentence. That's a very different type of movement to the daily bend of a sunflower as it tilts toward its solar power supply. That is controlled by a kind of inflatable joint at the base of the flower head, whose cells swell up with water on the side opposite the brightest light and bend the stalk toward the sun as it traverses the sky. And that's different again from the movement of certain self-propelled bacteria, who come fitted with a beautifully evolved rotor, the flagellum, which spins at up to a thousand revolutions per minute and can whip the cell along at a tenth of a millimeter per second.
We know very well that life is made of cells, and there are no life-forms that are not built from cells. Yet that is not what defines it, in the same way that a house is not defined by its bricks. We know that all life works via the reproduction of a universal code we can translate and read, but you won't be able to understand a baseball game by reading the rulebook. That point where the earth changed its status from “vitally inanimate” to “hosts living things” didn't happen by going down a checklist. There is certainly nothing wrong with that vital inventory; all of those examples on the checklist are by definition biochemical. The way proteins are built in strings and folded into three-dimensional thickets to give cells specific abilities; the way DNA can encode and replicate information; the way animal cells can take in oxygen, extract energy, and pump out carbon dioxide; the way plant cells can take in carbon dioxide, extract energy, and pump out oxygen. And so on. All of these processes are chemistry in action, determined by the behavior of the atoms that make up the molecules. So what is the nature of the chemistry that is actually biology?
Searching for a Definition
We have a checklist of the actions of life, but no clear, singular definition. Alone, or even in multitudes, a protein is not alive, nor is DNA, nor is a metabolic pathway. These are, for desperate want of a less clumsy term, inanimate. They do not have the breath of life in them, though they are clearly essential for it. And yet we are in no doubt that what allows an organism to live is the concatenation of all of these chemical events, and the ultimate termination of these chemical processes results in death. When we talk about the origin of life, everything pivots on the journey from inanimate matter to living matter.
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The transfer of information from cell to cell and from organism to organism via DNA is elemental to life as we know it. So is it possible to secure a definition of life that is underpinned by the ability to transfer information? NASA's interest in life extends from looking for it in space to synthetically engineering it here at home, as we shall see in part II. Astrobiology forms a satellite branch of origin-of-life research, the search for traces of life in far-off places. This new field is a coalescence of several branches of scienceâgeochemistry, biochemistry, astrophysicsâto contemplate the chances of life in the universe. NASA poses three questions in astrobiology: How did life begin and evolve? Does life exist elsewhere in the universe? What is the future of life on Earth and beyond? The first questionâthe origin of lifeâis of central importance to the astrobiologist, as it will determine how we will look for and recognize life when we find it.
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NASA's objectives in these outer-world explorations have led them to adapt a definition of life in order to help specify mission parameters: simply put, “if it's Darwinian, it's alive.” This is a position held by Gerald Joyce, a chemist working at the Scripps Research Institute in San Diego, whose experiments are precisely focused on allowing Darwinian evolution to occur in DNA's cousinâRNA. He told me:
If there's a sine qua non of life, it's the ability to undergo Darwinian evolution, and to have history in molecules. Chemistry doesn't have history. Biology has history. To me, the dawn of life is the dawn of biological history written in the genetic molecules that are carved through Darwinian processes.
This definition is focused in its entirety on information. DNA and RNA are codes, storing up a digital manual of instructions that can be copied and recopied over and over again. And as there is infidelity in copying, they acquire errors, which in turn become new information to be passed on and selected if it is useful. That is evolution.
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Replication is crucial for life, but is it enough to count as a definition? A crystal can grow, and can replicate its structure. That growth can suffer imperfections but, according to this definition, it is not alive because those imperfections are not passed on. It is not Darwinian because it cannot acquire new characteristics via selection. Darwinian behavior is certainly an essential feature of all life that we see, but is only one part of a set of behaviors that are universal in life.
Jack Szostak picked up a Nobel Prize in 2009 for a career's worth of work in human genetics. He helped build new techniques for us to explore our own genome, and contributed to the discovery of key components of aging. Then he switched from the human branch at one of the tips of the tree of life to the almost utterly unrelated field of biology at the base of the tree of life. At Harvard, Szostak founded the Origin of Life Initiative. One of his many concerns is the spontaneous formation of the cell membrane, which we will explore further in this book. He is quiet, easygoing, soft-spoken, patient, and thoughtful. But when I interview him, it's clear that the quest for a definition of life exasperates him, and more important, gets in the way of researching it. Uncharacteristically, he
almost
snaps at me when I suggest that the absence of a comprehensive definition of life is problematic. He cuts me off mid-question: “I don't think it's a problem at all. I think it's completely irrelevant. What we want to understand is the pathway, how we went from really simple chemicals to more complicated chemicals: from really simple cells to more complicated cells to modern biology. We just want to understand the process and all the steps. We don't need to say, âHere's the dividing line: on this side there's chemistry and on this there's biology.' The important thing is the path.”
J. B. S. Haldane, who earlier in the twentieth century had helped construct the idea of prebiotic soup, took a similar line in 1949 with his straightforwardly titled book
What Is Life?
Chapter 14 bears the same title as the book itself but begins with this bold caveat
I AM NOT GOING TO ANSWER THIS QUESTION. IN FACT, I DOUBT if it will ever be possible to give a full answer, because we know what it feels like to be alive, just as we know what redness or pain or effort are. So we cannot describe them in terms of anything else.
In other words,
I know it when I see it
.
Nevertheless, many people do focus on establishing a definition. Humans like to categorize things, science in particular, because so often it aids comprehension. Edward Trifonov, a biologist from the University of Haifa in Israel, recently approached the problem with an unusual tactic: to look at the words used in the many attempts by scientists to define life. By throwing them into a melting pot, he then ladled out a purified phrase: “Self-replication with variations.” This is similar to the NASA definition and focuses on the transfer of information from one generation to another. I'm sure this approach was well-meaning, but it is hard to see the value in establishing a consensus definition based on the language used. Trifonov's publication was gracious enough to include many responses from a cohort of scientists disagreeing and, in Szostak's case, resisting the urge to constrain life into a definition at all.
Indeed, all such attempts run the risk of the “Blind Men and the Elephant” syndrome. The Buddha (but also deities in Islam, Jainism, Hinduism, and other cultures) recounts the story of several sightless men asked by a king to tell him what an elephant is like. Each examined different parts of the beast with their hands and concluded that a pachyderm was only the bit that they could feel. The tusk examiner suggested it was like a plowshare, the foot inspector a pillar, the tail man a brush, and so on. They fight; the king laughs. An elephant is all of those things, and you can't capture its majesty by singling out one of its characteristics.
When Justice Potter Stewart said “I know it when I see it” (quoted at the top of this chapter), the “it” he was referring to was pornography, in response to the prosecution of the 1958 film
The Lovers
to be banned as an obscenity. It has evolved into a phrase to describe the subjectively ill defined, or things without clear parameters. Life is just that. At one stage there was chemistry on Earth, and at a later stage there were living things. The route from the first to the second point is inevitably long, tortuous, and messy. The point where we definitely have living things is certainly where things become Darwinian, but not solely (as we shall soon see, there are even certain molecules that display the Darwinian property of self-replication with selection). In other words, the boundary between chemistry and biology is arbitrary. Life is a combination of lots of different chemical systems that are more than the sum of their parts. We separate science into categories in discussions such as this, and, indeed, when we learn it: biology, chemistry, geology, physics, et cetera. These are also somewhat arbitrary, as science is merely a way of knowing nature, and makes particularly blurry distinctions when considering the very inception of one of them: biology.
The Energetic Fly in the Soup
All of the actions of cells are ultimately mediated by the controlled flow of electrically charged atoms from one side of a membrane to the other. As you read, charge-bearing atoms flow into millions of single brain cells until they hit a threshold. When this happens, the brain cells fire up, and in consort with millions of others will form a thought process, or trigger a memory or understanding or induce the desire to make a cup of tea. Similarly, it is the controlled flow of protonsâhydrogen atoms charged by being stripped of their single electronâacross membranes that drives the generation of energy which the cell and organism entirely relies upon. In all complex life (including us), this happens in the cell's power stations, mitochondria; in bacteria and archaea, across a membrane just inside the cell's outermost casing. This type of chemical pathway is part of what we call metabolism, and is of central importance to all life as it generates energy. That energy powers all of the actions of biology, including the ones that facilitate the replication of information across generations, and everything else on the MRS. GREN's life list.
For this reason, in considering the foundations of chemistry as it relates to biology, we have to turn to a more fundamental science: physics. The way chemicals behave is determined by the laws that belong traditionally to this field. Ernest Rutherford,
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the discoverer of the particles that make up the atom, famously declared, “Physics is the only real science. The rest are just stamp collecting.” Though provocatively mischievous, there is some value in this reductionist view, one that is typically shared by physicists. Biological behavior is determined by chemical behavior, which is determined by atomic forces, and these are in the realm of physics.
Haldane's
What Is Life?
was published in 1949, but he was not the first to come up with this deceptively simple title. In 1944, Erwin Schrödinger wrote a physics-focused biological treatise with the same name, a classic text drawn from a series of public lectures.
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That this analysis should come from a physicist is perhaps fitting in further blurring the artificial boundaries between the modern disciplines in science. Physics, by its nature, tends toward the fundamental, and Schrödinger's conclusions derive from one of the absolute and most nonnegotiable universal rules: the second law of thermodynamics. This is the principle that dictates with total authority that over a period of time, energy will always flow from a higher state to a lower state and never in the other direction. We see the application of the second law all around us. Once the heat is turned off, a pan of bubbling soup can only cool down. This principle extends to every aspect of our lives: the heat of a radiator is dissipated into warming our rooms because it is attempting to equilibrate the two imbalanced energy states: one is hotter than the other. It will never happen in reverse. The measure of the second law is what we refer to as entropy. At a constant temperature, a plump balloon will only deflate unless its knot is perfectly sealed, in which case it will remain constantly inflated. But it will never expand if its surroundings remain unchanged. Within the closed seal of the balloon it has reached equilibrium and its entropy is constant. But relative to the rest of the world, it has a higher energy state and therefore wishes (if one can express desire in a balloon) to spread its energy more fairly. This tendency toward fair distribution in energy is represented by an increase in entropy.