How did life begin? There can hardly be a bigger question. For much of human history, almost everyone believed some version of "the gods did it". Any other explanation was inconceivable.
That is no longer true. Over the last century, a few scientists have tried to figure out how the first life might have sprung up. They have even tried to recreate this Genesis moment in their labs: to create brand-new life from scratch.
So far nobody has managed it, but we have come a long way. Today, many of the scientists studying the origin of life are confident that they are on the right track – and they have the experiments to back up their confidence.
This is the story of our quest to discover our ultimate origin. It is a story of obsession, struggle and brilliant creativity, which encompasses some of the greatest discoveries of modern science. The endeavour to understand life's beginnings has sent men and women to the furthest corners of our planet. Some of the scientists involved have been bedevilled as monsters, while others had to do their work under the heel of brutal totalitarian governments.
This is the story of the birth of life on Earth.
Dinosaurs actually lived quite recently (Credit: Oleksiy Maksymenko/Alamy)
Dinosaurs actually lived quite recently (Credit: Oleksiy Maksymenko/Alamy)
Life is old. The dinosaurs are perhaps the most famous extinct creatures, and they had their beginnings 250 million years ago. But life dates back much further.
The oldest known fossils are around 3.5 billion years old, 14 times the age of the oldest dinosaurs. But the fossil record may stretch back still further. For instance, in August 2016 researchers found what appear to be fossilised microbes dating back 3.7 billion years.
These wavey patterns could be 3.7-billion-year-old fossils (Credit: Nutman et al, Nature)
These wavey patterns could be 3.7-billion-year-old fossils (Credit: Nutman et al, Nature)
The Earth itself is not much older, having formed 4.5 billion years ago.
If we assume that life formed on Earth – which seems reasonable, given that we have not yet found it anywhere else – then it must have done so in the billion years between Earth coming into being and the preservation of the oldest known fossils.
As well as narrowing down when life began, we can make an educated guess at what it was.
The tree of life (Credit: Hug, Banfield et al, Nature Microbiology)
The tree of life: most of the branches are bacteria (Credit: Hug, Banfield et al, Nature Microbiology)
Since the 19th Century, biologists have known that all living things are made of "cells": tiny bags of living matter that come in different shapes and sizes. Cells were first discovered in the 17th Century, when the first modern microscopes were invented, but it took well over a century for anyone to realise that they were the basis of all life.
Using only the materials and conditions found on the Earth over 3.5 billion years ago, we have to make a cell
You might not think you look much like a catfish or a Tyrannosaurus rex, but a microscope will reveal that you are all made of pretty similar kinds of cells. So are plants and fungi.
But by far the most numerous forms of life are microorganisms, each of which is made up of just one cell. Bacteria are the most famous group, and they are found everywhere on Earth.
In April 2016, scientists presented an updated version of the "tree of life": a kind of family tree for every living species. Almost all of the branches are bacteria. What's more, the shape of the tree suggests that a bacterium was the common ancestor of all life. In other words, every living thing – including you – is ultimately descended from a bacterium.
This means we can define the problem of the origin of life more precisely. Using only the materials and conditions found on the Earth over 3.5 billion years ago, we have to make a cell.
Well, how hard can it be?
A complete living cell (Credit: Equinox Graphics Ltd)
A complete living cell (Credit: Equinox Graphics Ltd)
Chapter 1. The first experiments
For most of history, it was not really considered necessary to ask how life began, because the answer seemed obvious.
Before the 1800s, most people believed in "vitalism". This is the intuitive idea that living things were endowed with a special, magical property that made them different from inanimate objects.
The chemicals of life can all be made from simpler chemicals that have nothing to do with life
Vitalism was often bound up with cherished religious beliefs. The Bible says that God used "the breath of life" to animate the first humans, and the immortal soul is a form of vitalism.
There is just one problem. Vitalism is plain wrong.
By the early 1800s, scientists had discovered several substances that seemed to be unique to life. One such chemical was urea, which is found in urine and was isolated in 1799.
This was still, just, compatible with vitalism. Only living things seemed to be able to make these chemicals, so perhaps they were infused with life energy and that was what made them special.
But in 1828, the German chemist Friedrich Wöhler found a way to make urea from a common chemical called ammonium cyanate, which had no obvious connection with living things. Others followed in his footsteps, and it was soon clear that the chemicals of life can all be made from simpler chemicals that have nothing to do with life.
The German chemist Friedrich Wöhler, in a lithograph by Rudolf Hoffmann from 1856
The German chemist Friedrich Wöhler, in a lithograph by Rudolf Hoffmann from 1856
This was the end of vitalism as a scientific concept. But people found it profoundly hard to let go of the idea. For many, saying that there is nothing "special" about the chemicals of life seemed to rob life of its magic, to reduce us to mere machines. It also, of course, contradicted the Bible.
The mystery of life's origin was ignored for decades
Even scientists have struggled to shed vitalism. As late as 1913, the English biochemist Benjamin Moore was fervently pushing a theory of "biotic energy", which was essentially vitalism under a different name. The idea had a strong emotional hold.
Today the idea clings on in unexpected places. For example, there are plenty of science-fiction stories in which a person's "life energy" can be boosted or drained away. Think of the "regeneration energy" used by the Time Lords in Doctor Who, which can even be topped up if it runs low. This feels futuristic, but it is a deeply old-fashioned idea.
Still, after 1828 scientists had legitimate reasons to look for a deity-free explanation for how the first life formed. But they did not. It seems like an obvious subject to explore, but in fact the mystery of life's origin was ignored for decades. Perhaps everyone was still too emotionally attached to vitalism to take the next step.
Charles Darwin showed that all life has evolved from a simple common ancestor
Charles Darwin showed that all life has evolved from a simple common ancestor
Instead, the big biological breakthrough of the 19th Century was the theory of evolution, as developed by Charles Darwin and others.
Darwin knew that it was a profound question
Darwin's theory, set out in On the Origin of Species in 1859, explained how the vast diversity of life could all have arisen from a single common ancestor. Instead of each of the different species being created individually by God, they were all descended from a primordial organism that lived millions of years ago: the last universal common ancestor.
This idea proved immensely controversial, again because it contradicted the Bible. Darwin and his ideas came under ferocious attack, particularly from outraged Christians.
The theory of evolution said nothing about how that first organism came into being.
Darwin wondered if life began in a "warm little pond" (Credit: Linda Reinink-Smith/Alamy)
Darwin wondered if life began in a "warm little pond" (Credit: Linda Reinink-Smith/Alamy)
Darwin knew that it was a profound question, but – perhaps wary of starting yet another fight with the Church – he only seems to have discussed the issue in a letter written in 1871. His excitable language reveals that he knew the deep significance of the question:
The first hypothesis for the origin of life was invented in a savagely totalitarian country
"But if (& oh what a big if) we could conceive in some warm little pond with all sorts of ammonia & phosphoric salts,—light, heat, electricity &c present, that a protein compound was chemically formed, ready to undergo still more complex changes..."
In other words, what if there was once a small body of water, filled with simple organic compounds and bathed in sunlight. Some of those compounds might combine to form a life-like substance such as a protein, which could then start evolving and becoming more complex.
It was a sketchy idea. But it would become the basis of the first hypothesis for how life began.
This idea emerged from an unexpected place. You might think that this daring piece of free thinking would have been developed in a democratic country with a tradition of free speech: perhaps the United States. But in fact the first hypothesis for the origin of life was invented in a savagely totalitarian country, where free thinking was stamped out: the USSR.
Alexander Oparin lived and worked in the USSR (Credit: Sputnik/Science Photo Library)
Alexander Oparin lived and worked in the USSR (Credit: Sputnik/Science Photo Library)
In Stalin's Russia, everything was under the control of the state. That included people's ideas, even on subjects – like biology – that seem unrelated to Communist politics.
Oparin imagined what Earth was like when it was newly formed
Most famously, Stalin effectively banned scientists from studying conventional genetics. Instead he imposed the ideas of a farm worker named Trofim Lysenko, which he thought were more in line with Communist ideology. Scientists working on genetics were forced to publicly support Lysenko's ideas, or risk ending up in a labour camp.
It was in this repressive environment that Alexander Oparin carried out his research into biochemistry. He was able to keep working because he was a loyal Communist: he supported Lysenko's ideas and even received the Order of Lenin, the highest decoration that could be bestowed on someone living in the USSR.
In 1924, Oparin published his book The Origin of Life. In it he set out a vision for the birth of life that was startlingly similar to Darwin's warm little pond.
Oceans formed once Earth had cooled down (Credit: Richard Bizley/Science Photo Library)
Oceans formed once Earth had cooled down (Credit: Richard Bizley/Science Photo Library)
Oparin imagined what Earth was like when it was newly formed. The surface was searingly hot, as rocks from space plunged down onto it and impacted. It was a mess of semi-molten rocks, containing a huge range of chemicals – including many based on carbon.
If you watch coacervates under a microscope, they behave unnervingly like living cells
Eventually the Earth cooled enough for water vapour to condense into liquid water, and the first rain fell. Before long Earth had oceans, which were hot and rich in carbon-based chemicals. Now two things could happen.
First, the various chemicals could react with each other to form lots of new compounds, some of which would be more complex. Oparin supposed that the molecules central to life, like sugars and amino acids, could all have formed in Earth's waters.
Second, some of the chemicals began to form microscopic structures. Many organic chemicals do not dissolve in water: for example, oil forms a layer on top of water. But when some of these chemicals contact water they form spherical globules called "coacervates", which can be up to 0.01cm (0.004 inches) across.
If you watch coacervates under a microscope, they behave unnervingly like living cells. They grow and change shape, and sometimes divide into two. They can also take in chemicals from the surrounding water, so life-like chemicals can become concentrated inside them. Oparin proposed that coacervates were the ancestors of modern cells.
The idea that living organisms formed by purely chemical means, without a god or even a "life force", was radical
Five years later in 1929, the English biologist J. B. S. Haldane independently proposed some very similar ideas in a short article published in the Rationalist Annual.
Haldane had already made enormous contributions to evolutionary theory, helping to integrate Darwin's ideas with the emerging science of genetics.
He was also a larger-than-life character. On one occasion, he suffered a perforated eardrum thanks to some experiments with decompression chambers, but later wrote that: "the drum generally heals up; and if a hole remains in it, although one is somewhat deaf, one can blow tobacco smoke out of the ear in question, which is a social accomplishment."
Just like Oparin, Haldane outlined how organic chemicals could build up in water, "[until] the primitive oceans reached the consistency of hot dilute soup". This set the stage for "the first living or half-living things" to form, and for each one to become enclosed in "an oily film".
The English geneticist J. B. S. Haldane (Credit: Science Photo Library)
The English geneticist J. B. S. Haldane (Credit: Science Photo Library)
It is telling that of all the biologists in the world, it was Oparin and Haldane who proposed this. The idea that living organisms formed by purely chemical means, without a god or even a "life force", was radical. Like Darwin's theory of evolution before it, it flew in the face of Christianity.
There was one problem. There was no experimental evidence to back it up
That suited the USSR just fine. The Soviet regime was officially atheist, and its leaders were eager to support materialistic explanations for profound phenomena like life. Haldane was also an atheist, and a devoted communist to boot.
"At that time, to accept or not accept this idea depended essentially on personalities: whether they were religious or whether they supported left or communist ideas," says origin-of-life expert Armen Mulkidjanian of the University of Osnabrück in Germany. "In the Soviet Union they were accepted happily because they didn't need God. In the western world, if you look for people who were thinking in this direction, they all were lefties, communists and so on."
The idea that life formed in a primordial soup of organic chemicals became known as the Oparin-Haldane hypothesis. It was neat and compelling, but there was one problem. There was no experimental evidence to back it up. This would not arrive for almost a quarter of a century.
(Credit: Emilio Segre Visual Archives/American Institute Physics/Science Photo Library)
Harold Urey (Credit: Emilio Segre Visual Archives/American Institute of Physics/Science Photo Library)
By the time Harold Urey became interested in the origin of life, he had already won the 1934 Nobel Prize in Chemistry and helped to build the atomic bomb. During World War Two Urey worked on the Manhattan Project, collecting the unstable uranium-235 needed for the bomb's core. After the war he fought to keep nuclear technology in civilian control.
In 1952, Miller began the most famous experiment on the origin of life ever attempted
He also became interested in the chemistry of outer space, particularly what went on when the Solar System was first forming. One day he gave a lecture and pointed out that there was probably no oxygen in Earth's atmosphere when it first formed. This would have offered the ideal conditions for Oparin and Haldane's primordial soup to form: the fragile chemicals would have been destroyed by contact with oxygen.
A doctoral student named Stanley Miller was in the audience, and later approached Urey with a proposal: could they test this idea? Urey was sceptical, but Miller talked him into it.
So in 1952, Miller began the most famous experiment on the origin of life ever attempted.
The Miller-Urey experiment (Credit: Francis Leroy, Biocosmos/Science Photo Library)
The Miller-Urey experiment (Credit: Francis Leroy, Biocosmos/Science Photo Library)
The set-up was simple. Miller connected a series of glass flasks and circulated four chemicals that he suspected were present on the early Earth: boiling water, hydrogen gas, ammonia and methane. He subjected the gases to repeated electric shocks, to simulate the lightning strikes that would have been a common occurrence on Earth so long ago.
You can go from a simple atmosphere and produce lots of biological molecules
Miller found that "the water in the flask became noticeably pink after the first day, and by the end of the week the solution was deep red and turbid". Clearly, a mix of chemicals had formed.
When Miller analysed the mixture he found that it contained two amino acids: glycine and alanine. Amino acids are often described as the building blocks of life. They are used to form the proteins that control most biochemical processes in our bodies. Miller had made two of life's most important components, from scratch.
The results were published in the prestigious journal Science in 1953. Urey, in a selfless act unusual among senior scientists, had his name taken off the paper, giving Miller sole credit. Despite this, the study is often known as the "Miller-Urey experiment".
Stanley Miller in his lab (Credit: Science Photo Library)
Stanley Miller in his lab (Credit: Science Photo Library)
"The strength of Miller-Urey is to show that you can go from a simple atmosphere and produce
