Stanley Miller conducting the Miller-Urey Experiment, designed to test the idea that the fundamental elements of life could be assembled in a ‘primordial soup’

Special Collections & Archives, UC San Diego

Stanley Miller conducting the Miller-Urey Experiment, designed to test the idea that the fundamental elements of life could be assembled in a ‘primordial soup,’ in his lab at the University of California at San Diego, 1981

Each human culture has its own origin myths. The Telefol, a mountain people of New Guinea, relate that in the beginning there was a mother called Afek, who had four children: a long-beaked echidna (an egg-laying mammal), a ground cuscus (a cat-sized marsupial), a rat, and a human. The echidna’s eyes were irritated by hearth-smoke, so Afek told it to go to the high forest. The human and the rat stayed in and around Afek’s hut, as initially did the ground cuscus. But he was cheeky, and overly curious about his own origins. When he inserted a digit into his mother’s vagina, Afek chopped it off and exiled him to the forest.

The Telefol say that this story explains why ground cuscuses have four digits on each forepaw. Except they don’t: I’ve seen plenty, and they all have five. Whenever I came across a ground cuscus in the company of Telefol, I’d point out the five digits. They would carefully and thoughtfully examine the creature before exclaiming that it couldn’t be a true ground cuscus—because real ones have only four! Origin myths, it seems, are so powerful that they can survive in the face of almost any amount of contradictory evidence.

The biblical book of Genesis includes two origin myths—the six days of creation, and the making of Adam from dust, which God animated with his divine breath. The idea of a God-given life force (a soul) as something separate from the body was almost universal in Western cultures until the early twentieth century, and it remains strong today. It’s easy to see why belief in a life force is so tenacious. The transition from life to death is familiar to us all, and in that process all the complexity that is contained in a living being seems to vanish. It’s a natural reaction to ask where we go with the expiration of that last breath, and where we came from in the first place.

In The Genesis Quest, the science writer Michael Marshall argues that belief in a life force long stymied progress in understanding life’s origins. It was only with publication of Darwin’s theory of evolution by natural selection in 1859 that the notion that the first living thing must have had a precursor became widespread. As science advanced, it was established that a collection of molecules with some lifelike properties must have given rise to life. Marshall’s book focuses on the chemical research—from the first speculative insights made by brilliant minds to the complex experiments that have increasingly dominated the field—into life’s origins. It’s a fascinating and challenging story, and leavened with mini-biographies, the best of which are based on his own interviews with his subjects.

The first real advances in the search for life’s origins were made by Communists. This is because, according to Marshall, while Western society was still half in thrall to Christian ideas, “communism was built on a philosophical foundation called dialectical materialism, which entailed explaining everything in terms of material objects.”

In 1924 the Soviet biochemist Alexander Oparin published a booklet positing that life began in the primordial ocean as jelly-like blobs, which in time would give rise to the first cells. A few years later, and quite independently, the British biologist and fellow Communist John Burdon Sanderson (J.B.S.) Haldane came up with the idea that life started in the “hot dilute soup” of the primordial ocean. In that soup, he believed, molecules arose that could make copies of themselves by using the chemicals around them.

I find it astounding that Marshall leaves it to his epilogue to inform us that there is no universally agreed-upon definition of life. Researchers like Oparin and Haldane had to supply their own. But one thing that everyone agrees on today is that life must have three properties: it must have boundaries (hence Oparin’s cell-like blobs), it must be able to feed, and it must be able to reproduce (hence Haldane’s “soup,” as well as his self-replicating molecules).

Oparin’s and Haldane’s books were little but thought experiments, undertaken at a time when the earliest parts of the fossil record were entirely unknown. Geologists have since uncovered a considerable body of evidence concerning early life, as well as the conditions under which it arose. The oldest undisputed fossils are stromatolites from Australia dating back 3.5 billion years. Stromatolites are complex communities of bacteria and archaea (a type of prokaryote, or single-cell organism lacking a nucleus) that function as ecosystems. Their complexity suggests that life was in existence long before these first stromatolite fossils grew. And indeed, earlier hints of life have been unearthed. Tubes and strands in rocks dating back at least 3.77 billion years have been found in Canada, and carbon atoms preserved in a crystal that is 4.1 billion years old seem to have originated in a living thing. Currently, the best guess is that life arose within half a billion years of Earth’s formation some 4.46 billion years ago.


The idea that lifeless chemicals assembled themselves into a living cell so early in Earth’s history indicates to Marshall that life “can happen relatively easily, and therefore repeatedly.” And already this realization has paid off by helping scientists develop a new solution to the Drake equation, which estimates the number of civilizations in the Milky Way. If life easily originates early in the existence of Earth-like planets, there may be at least thirty-six alien civilizations in our galaxy.

Little real progress was made beyond the early speculations of Oparin and Haldane until the fall of 1952, when Stanley Miller, a young Ph.D. student, and Harold Urey, his Nobel Prize–winning supervisor at the University of Chicago, decided to run an experiment to test the idea that the building blocks of life could be assembled in a “primordial soup.” The Miller-Urey Experiment, as it is known, became one of the most famous scientific experiments of all time.

The two researchers attempted to reconstruct in a lab the conditions that existed on Earth when life arose. The university glass-blower made a vessel with two interconnected bulbs, one to hold water to represent the primordial soup, and the other to hold a mix of gases representing the early atmosphere, along with a wire to simulate the electrical storms that Miller and Urey thought would have occurred frequently on the early Earth. Within two days of starting the experiment, the “ocean” had turned yellow, and a black, tar-like substance had formed at the bottom of the bulb holding the atmosphere. When analyzed, the yellow water was found to contain glycine, the simplest amino acid and an important building block of life.

When the results were published on May 15, 1953, they quickly became a headline-grabbing sensation. The acclaim was surely due in part to the belief, still widespread in the 1950s, that there was a “life force” and that Urey and Miller had shed light on its nature. Whatever the case, the breakthrough prompted a wave of experimental work on the origins of life that continues to this day.

By the early 1970s Urey and Miller’s experiment appeared less informative than first imagined. This is because the gases used to represent the early atmosphere were “reducing” gases—methane, ammonia, and hydrogen, which more easily give rise to chemical reactions. Subsequently, the composition of Earth’s early atmosphere was reassessed based on the gases emitted by volcanoes, and it was found to have contained mostly nitrogen and carbon dioxide.

To the dismay of researchers, experiments using a more accurate atmosphere resulted in the formation of very few amino acids. And the discovery, in 1953, the same year as the Miller-Urey Experiment, of the structure of DNA changed the nature of the search for the origins of life. Importantly, it led to the recognition that even the simplest cell is an “incomprehensibly complex” machine, so the synthesis of amino acids in a primordial soup could only be the first step in the extraordinarily long and complex chain of events that led to life.

One of the most innovative insights about how that complexity could have arisen was made by Alexander Graham Cairns-Smith of the University of Glasgow. He’s one of the researchers personally interviewed by Marshall, who gives us an engaging portrait of this talented painter, chemist, and counterintuitive thinker. While others turned to primordial soups and reactive gases for answers to life’s origins, Cairns-Smith began examining clay in the 1960s. He reasoned that clay is made of small crystals in a great variety of shapes that can grow and, in a sense, “reproduce” by splitting apart, and that clay crystals “might even be able to evolve” by passing on characteristics that accelerate their rate of growth or rate of splitting, thus allowing the fastest-growing and -reproducing crystals to predominate.

The fact that clay is not living may have troubled others, but not Cairns-Smith. He thought that clay crystals might have used “biological” molecules such as DNA and proteins to accelerate their growth and reproduction, before eventually leaving the clay behind and becoming the earliest life. The Genesis Quest is often dense and difficult, but when I came across Cairns-Smith’s astonishing ideas about clay I put the book down, my mind alive with speculation I needed to process. I thought about the futurists who envision machines replacing human bodies, and computers replacing human minds. Could it be that “life,” however we define it, might soon turn full circle—from inorganic clay to organic proteins and on to inorganic metals?


The idea that life has foundations (if not feet) of clay was so idiosyncratic and ahead of its time that it was comprehensively ignored. To be fair to the scientists of the day, it was also extremely difficult to test. Nobody could identify and track individual crystals in clay, nor could they characterize their properties. The study of DNA, then in its dynamic youth, was attracting the best young researchers and was yielding spectacular results. The prospect of devoting years of effort and millions of dollars to investigating clay held little appeal.

Despite the boost given to the search by the unlocking of DNA’s secrets, in the 1970s the entire field entered a crisis. Researchers were getting nowhere near creating a cell, and their various failures were summarized by Robert Shapiro, a chemist at New York University. In his book Origins, he pointed out the fatal weaknesses in almost every existing hypothesis yet offered no alternatives, spreading a sense of dismay across the field and earning him the nickname “Doctor No” among his students.

Then a new idea arose: the individual components that today are found only within cells must have originated as independent entities—in effect tiny, highly complex autonomous pieces of cellular machinery, floating free in the environment. Now we know that some of the most complex organelles found in eukaryotes—that is, cells with nuclei—did in fact originate this way. The best example is mitochondria (the cell’s powerhouse), which originated as free-living prokaryotes, and were then somehow absorbed into eukaryotes.

But could the proteins that also make up the cellular machinery have originated as independent entities? The idea had been discussed as early as the 1970s, but it took until 1996 to create a protein that could replicate itself. Even then the experimenters managed this feat only when the protein had access to two halves of itself, which it stitched together. It was highly unlikely that a protein would have access to these halves in the first ocean.

Meanwhile, other researchers, including the American biochemist Walter Gilbert, were experimenting with the idea that life originated not with proteins but with RNA. RNA is essential to the coding, decoding, regulation, and expression of genes, and can perform the roles of both DNA and proteins. The new hypothesis, which became known as “RNA World,” received immediate acclaim.

Fatty acid vesicles encapsulating RNA molecules attached to clay; image from an experiment conducted to determine how the first cells may have been formed

Martin Hanczyc

Fatty acid vesicles encapsulating RNA molecules attached to clay; image from an experiment conducted to determine how the first cells may have been formed

The first question researchers turned to was whether RNA could have assembled itself out of a “nucleotide soup.” Little progress was made until the American chemist James Ferris discovered that when RNA is laid atop a special kind of clay called montmorillonite, which acts as a catalyst, it becomes easier for pieces of RNA to link up. Suddenly, Cairns-Smith did not seem so crackbrained after all. Nor did the biblical story of life’s origin in dust (dry clay, perhaps?) and divine breath seem so far from the mark.

Gilbert’s work was a step forward. But even with the help of clay, RNA stubbornly refused to be self-replicating. While some progress has been made in validating the RNA World hypothesis over the past twenty years, the biochemist Harold Bernhardt, according to Marshall, “spoke for many weary researchers when he wrote that the RNA World hypothesis was ‘the worst theory of the early evolution of life (except for all the others).’” Research on the formation of the earliest cells continued in parallel. One group of researchers mixed phospholipid vesicles—an assembly of the molecule that is a crucial component of cell membranes—with DNA and repeatedly dehydrated then rehydrated the mixture. When the vesicles were dried out, the phospholipids rearranged themselves into flat layers, trapping DNA between them. When the water returned, the vesicles reformed—but now each contained DNA. The result was not a living thing. But at least it was progress.

Throughout the twentieth century, Marshall tells us, the search for life’s origins was dominated by four major hypotheses for what aspect of life came first. Some researchers followed Oparin and focused on the creation of cells (membranes). Others focused on proteins, while a third group studied replication (RNA). A final group followed Haldane’s insights into molecules using other molecules in the primordial soup to sustain themselves, and asked how metabolism started.

Metabolism is the process by which life creates order. Erwin Schrödinger spelled it out in 1944 in his wonderful book What Is Life?: “Life,” he wrote, “seems to be orderly and lawful behaviour of matter, not based exclusively on its tendency to go over from order to disorder, but based partly on existing order that is kept up.” But as the second law of thermodynamics dictates, the order life creates only results in more disorder elsewhere. Marshall urges us to consider the prodigious volumes of feces (to which I would add flatulence, urine, and other excretions) each of us voids over a lifetime in order to help our bodies defy the second law of thermodynamics.

The search for life’s origins in metabolism has been fruitful, and today many researchers believe that some form of metabolism must have come before cell formation and reproduction. Every organism, from the simplest bacteria to humans, employs the same molecule—adenosine triphosphate (ATP)—for its energy needs. Known as a universal energy “currency,” ATP is used and regenerated by life on an enormous scale. The average human, for example, consumes and recycles their own bodyweight of ATP every day.

One of the most important breakthroughs in the hypothesis that metabolism came first was made by a German patent lawyer. Günter Wächtershäuser became fascinated with the origins of life in the 1960s, while completing a Ph.D. in chemistry. He later met and befriended a number of scientists whose work furthered his thinking, including arguably the most influential philosopher of science, Karl Popper. His great idea became known as the Iron-Sulphur World hypothesis.

Pyrite (fools’ gold) forms when iron reacts with hydrogen sulphide, emitting hydrogen as a byproduct. The reaction also releases electrons, which, in the presence of carbon dioxide and hydrogen, can make water and formaldehyde. And formaldehyde can be used to create amino acids, which are the building blocks of life. It seems certain that as soon as liquid water formed on Earth, iron and hydrogen sulphide that leached from Earth’s crust interacted in the ocean. In the Iron-Sulphur World hypothesis, the earliest organisms arose “and acquir[ed] their energy by continuously forming and dumping pyrite.”

Marshall says that Wächtershäuser’s “precursor organisms” seem bizarre: “A cluster of chemicals stuck to the surface of a crystal [pyrite], living off the chemical reaction between iron and hydrogen sulphide? Such things don’t seem lifelike at all.” Sadly, when pressed for further details about his “precursor organisms,” Wächtershäuser answered only in riddles.

Real-world discoveries were, however, coming to the patent lawyer’s aid. Pyrodictium is an archaean that lives in scalding-hot waters off Sicily, near the island of Vulcano, and that uses the reaction between sulphur and hydrogen for energy. “When Wächtershäuser’s friend Karl Stetter and his colleagues grew Pyrodictium in their lab, pyrite was formed,” Marshall writes.

In 1977 hydrothermal vents in the deep sea were discovered. Complex, abundant life is supported solely by chemical reactions in which bacteria convert hydrogen sulphide to sulphur, releasing energy to the giant tube worms, clams, crustaceans, and other creatures that flourish there. Soon, researchers were asking whether life could have originated around ocean vents. An abundance of chemicals that could give rise to amino acids and provide energy—along with the presence of montmorillonite clays—make them suitable candidates.

It was the British geologist Mike Russell who almost single-handedly pioneered the ocean vent theory of life’s origins. He realized that many mineral deposits develop around such vents, and that temperatures around some are cool enough to allow early life to survive. He had discovered fossilized tubes of pyrite in rocks that had formed at a special kind of ocean vent known as alkaline vents, or white smokers. To recreate the tubes in the lab, he

dissolved sodium disulphide in water and passed it through a narrow hole, on the other side of which was salt water laced with iron dichloride. Where the two solutions met, a layer of jelly formed. Bubbles and blobs emerged, broke off and became thin vertical tubes.

Russell’s tubes, it was soon noted, could have been the origin of the ATP system.

The rapidly advancing field of genetics soon provided further evidence supporting this idea. Researchers working on reconstructing the genome of the Last Universal Common Ancestor (LUCA) determined that it was adapted to life in hot water. Moreover, LUCA, much like Russell’s tubes, had the capacity to harness a proton gradient (which results in the concentration of protons that can be used as an energy source), but not to generate one.

RNA World was given a boost when Jack Szostak of Harvard Medical School and the Italian biochemist Pier Luisi asserted that “the first life…must have been an RNA hosted inside a vesicle” that was able to copy itself. As Marshall says, with this discovery “the synthesis of simple living cells” had become “an imaginable goal.” And here, the role of clay (thank you, Cairns-Smith) once again arose. Szostak’s team discovered that proto-cells could form, through a process of wetting and drying, so that they included a grain of montmorillonite clay inside them, and that such cells could accelerate important chemical processes a hundredfold.

Recently, the weight of evidence has shifted away from an origin at ocean vents and toward the idea that life arose in a pool on land that was repeatedly dried and refilled with water. Marshall says that if Szostak is on the right track, he is about two thirds of the way to creating a primordial cell in his lab, and that the missing element is metabolism. Yet even the simplest bacteria are orders of magnitude more complicated than Szostak’s creations.

Reading The Genesis Quest, one cannot help but feel that, like the gods in many creation myths, we are on the brink of creating life from nonliving matter. Yet there is something rather deflating about much of the science that has gotten us this far, at least as it is recounted by Marshall. The Genesis Quest is a competent account of a series of highly complex chemical experiments. The cumulative effect is to reduce our understanding of what life is to chemical interactions.

I have a feeling that when the first synthetic life form is finally announced, it will be underwhelming, both because it will be so much less complex than even the simplest cell in existence today, and because we inhabit a different world from that which greeted news of the Urey-Miller Experiment so enthusiastically some seventy years ago. Today, our imaginations are captured by the race to develop machine-based artificial intelligence. And that race at least holds out the prospect of creating an entity that we can communicate with—unlike the mute cells from which life emerged.