HOW did life on Earth begin? Until 70 years ago, generations of scientists had failed to throw much light on biology’s murky beginnings. But then came three crucial findings in quick succession.
In April 1953, the race to uncover the structure of DNA reached its climax. Geneticists soon realised that its double helix form could help explain how life replicates itself – a fundamental property thought to have appeared at or around the origin of life. Just three weeks later, news broke of the astonishing Miller-Urey experiment, which showed how a simple cocktail of chemicals could spontaneously generate amino acids, vital for building the molecules of life. Finally, in September 1953, we gained our first accurate estimate for the age of Earth, giving us a clearer idea of exactly how old life might be.
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At that point, we seemed poised to finally understand life’s origins. Today, conclusive answers remain elusive. But the past few years have brought real signs of progress.
For instance, we have found that life’s ability to replicate is not wholly reliant on DNA. We also have a far better idea of the conditions on early Earth when life first appeared – and we are beginning to conduct experiments into how it emerged that are much more sophisticated than Miller-Urey.
So, 70 years on from that incredible year of breakthroughs, how has our picture of life’s origins changed? And what remains to be figured out before we can satisfactorily answer biology’s ultimate question?
Definitions of life
“I think in the 50s we knew very little about life,” says at Dayhoff Labs, a company that builds AI models for biochemistry, in London. While it was clear that all life is made of cells, the inner workings of those cells were almost entirely mysterious.
The molecular biology revolution changed all that, and it arguably started in 1953. On 25 April, James Watson and Francis Crick published a . Otherwise known as deoxyribonucleic acid, DNA had already been identified as the molecule that carries all our genes. Watson and Crick were one of several groups trying to figure out its shape. Inspired in part by X-ray crystallography images obtained by Rosalind Franklin, they worked out that DNA is a double helix: it is made up of two long chains that twist around each other.
This discovery led to an explosion of research. In short order, biochemists revealed how information is encoded in the sequence of building blocks that make up the DNA molecule, and how the sequence is used to construct the complex proteins from which organisms are made.
But what biologists of the 1950s couldn’t know is just how extraordinarily intricate even the simplest of living cells are. A 2022 study reported the . The researchers chose a parasitic species called Mycoplasma genitalium, because it has relatively few genes and therefore presented less of a computational challenge. Nevertheless, just figuring out the shapes of the protein molecules took more than eight months. In other words, life is complicated – much more so than we thought 70 years ago.
This new appreciation of life’s complexity has broader implications. For instance, in the years that followed the discovery of the DNA double helix, many biologists began viewing living things through a lens of reproduction and heredity. Life, in this view, is all about the genetic information that is passed on from generation to generation.
In recent decades, however, it has become increasingly clear that life isn’t just about the genome. For example, living cells are highly dynamic, with components constantly moving and transforming, all largely in an effort to maintain a kind of stability. So we now know that reducing life to one or two components or processes is a mistake.
This helps explain why biology has yet to settle on a clear definition of “life” that commands widespread support. This isn’t for want of trying: a review published a decade ago identified . And they keep coming: one new idea to emerge is Assembly Theory, which proposes that there is a universal process through which matter can evolve complexity through time, with life defined as a point at which a certain level of complexity has been reached.
Age of the earth
At first glance, this struggle to define life suggests we are hopelessly far from unravelling its origins. But it is possible to take another view. With our appreciation of the complexity of life comes the realisation that there are many theoretical pathways by which mixtures of chemicals could have self-assembled into the first organisms.
For most of human history, it was impossible to say much about the conditions that existed when life originated, for the simple reason that we had no hard evidence about the age of Earth or the biosphere. With the , a path opened to finding the planet’s true age. Every radioactive element decays at a specific rate, some over the course of hundreds of millions of years. Given that some of these elements are found in rocks, the discovery offered a way to calculate their age and, by extension, that of Earth. But there is a catch: Earth is a geologically active place, so rocks are continually destroyed and created, meaning few of them are as old as the planet.
The key was to find rocks that had formed at the same time as Earth, and by the 1950s, geologists had a solution: meteorites. These chunks of rock – the same sort of material that had coalesced to form our planet – had drifted through the solar system since Earth’s birth, before crash-landing here.
At a conference in September 1953, Clair Patterson at the California Institute of Technology and his colleagues revealed that they had analysed fragments of the Canyon Diablo meteorite, which formed the famous Meteor crater in Arizona. By measuring how much of the meteorite’s uranium had decayed into lead, they determined that it – and so Earth – was 4.55 billion years old. However, the the finding was physicist Fritz Houtermans at the University of Bern, Switzerland, in December 1953. He calculated an age of 4.5 billion years after being sent information about Patterson’s research.
We finally knew that life may have existed on Earth for billions of years. But it was unclear in 1953 exactly when it had originated and what the conditions on our planet were like when it did so. This uncertainty wasn’t helped by the fact that the oldest known fossils at the time were little more than half a billion years old.
However, older fossils soon emerged. In 1957, for example, palaeontologists described a frond-like fossil, known as Charnia, from the UK that we now know is about 570 million years old. Since then, the age of the oldest known fossils has been pushed much further back in time: a 2019 study found strong evidence that 3.5-billion-year-old rocks in Pilbara, Australia, contain the preserved remains of single-celled microorganisms. Moreover, based on what we know about the evolutionary tree of life, some researchers argue that the last universal common ancestor – an organism that gave rise to everything living today – existed at least 3.9 billion years ago.
Crucially, we now have a much better idea of what our planet was like at that time. In the past 20 years, we have learned that that could, in principle, have supported life by about 4.2 billion years ago. “It’s much more widely accepted in the past few years that there was water on the early earth,” says at the University of California, Los Angeles. Dry land may have arrived early too, with evidence for its presence by 3.7 billion years ago.
This means we now understand there was no shortage of environments for life to emerge, both on land and in the sea. Over the past 70 years, we have learned a great deal about how it might have done so.
Theories of the origins of life
The foundational experiment in creating life from scratch was conducted in late 1952, and published on 15 May 1953. A young graduate student at the University of Chicago named Stanley Miller wanted to find out if the molecules of life could have formed on the early earth. At the time, little was known of Earth’s earliest history, but .
He designed an apparatus consisting of two glass flasks, linked by tubes. One flask held water, mimicking the oceans Miller assumed would have existed. It could be heated, as Miller also reasoned there were lots of volcanoes on the young planet. The other flask represented the early atmosphere and contained a mix of methane, ammonia and hydrogen. Miller also inserted an electrode to simulate lightning strikes.
After just a few days, the water turned first yellow and then brown. When Miller analysed the resulting mixture, he found it contained glycine. This is the simplest of the amino acids, which are the building blocks of proteins. Amino acids are essential to life as we know it, and Miller had shown that they could form spontaneously under natural conditions.
Miller’s supervisor, the chemist Harold Urey, selflessly told Miller to take sole credit for the work. Nevertheless, the set-up is often known as the Miller-Urey experiment. Seven decades later, “it is still the experiment that the public knows most intimately”, says Xavier.
However, although amino acids are important for life, they are also found in lifeless settings – including deep space – so they don’t tell us very much on their own. “Making amino acids is not making life,” says Xavier. The question then becomes, which of life’s fundamental processes came first?
As we have already seen, some researchers insist that genetics was one of life’s foundational features. But few of them now think this means DNA was present in the first organisms. Rather, some argue that life began with RNA, a molecular cousin of DNA with a wider range of properties including, importantly, the ability to control the rates of chemical reactions crucial to life. In line with this, over the past 40 years, chemists have demonstrated that RNA can perform many of the functions of life. They have, for instance, shown it is possible to make RNA molecules that, with minimal help, can reliably copy other RNA strands they encounter.
Meanwhile, at Waseda University in Tokyo, Japan, has shown that, once assembled, RNAs can behave in a way that resembles features of a living entity. Last year, he and his colleagues showed that a strand could evolve into five “lineages” with distinct genetic properties – perhaps a precursor to distinct genes in a full genome.
Primordial soup
But even Mizuuchi suspects it might be too simplistic to focus exclusively on RNA. Other biomolecules are likely to have been just as important, he says. For instance, other researchers consider metabolism, the reactions that underpin life’s ability to nourish and sustain itself. These processes are fiendishly complex, and in modern organisms they are controlled by battalions of enzymes – a special kind of protein. However, since 2014, a has revealed that many of the reactions can take place spontaneously in water, with no need for enzymes. A few simple metals – such as iron, nickel and cobalt, which are common in nature – are .
Xavier and her colleagues are searching for a more general version of these chemical networks. She argues the key to life is “autocatalysis” – the ability of a set of molecules to react together in order to replicate themselves.
In 2022, Xavier and her colleague Stuart Kauffman at the Institute for Systems Biology in Seattle mapped the networks of chemical reactions that take place in single-celled microbes. They looked at 6683 different networks: every single one contained a . The implication is that this ability is pretty common.
However, there is a twist. Xavier argues that the autocatalytic networks in living organisms are always incomplete. Biological molecules need a hand – and, again, that help comes from metals in the environment. “All life depends on metals,” says Xavier. She argues that the central importance of metals is just one of the ways life depends on its environment to survive.
The community of life
Other researchers also now emphasise the need to place the origin of life into its environmental context. “You cannot separate life from the planet,” says Betül Kaçar at the University of Wisconsin-Madison. Indeed, one of the biggest shifts in origins research in recent decades has been away from simply mixing chemicals in water, Miller-style, and towards experiments that more closely simulate a four-dimensional environment, one with a shape and surfaces that change over time. Proposed environments include a geochemical pool on land exposed to ultraviolet sunlight, the edges of which dry out in the sun and then become wet again when it rains, and the interior of a deep-sea hydrothermal vent where complex mixtures of chemicals flow up from beneath the seabed.
Finally, some researchers are also now acknowledging that the biggest clue to life’s origins may have been staring us in the face all along: life is a community. Today, all organisms depend on others for their survival. This suggests we should stop focusing on the origins of the first organism and instead consider the origins of the first ecosystem. It is possible, thinks Xavier, that this primordial ecosystem had a three-dimensional structure – like the sticky biofilms that form when bacteria gunk up pipes – and that, at first, there were no individual cells.
If reconstructing the first organisms is difficult enough, it is nothing compared to the challenge of reconstructing primordial ecosystems. As such, it is likely that the origins of life will continue delightfully puzzling us for many decades to come. “If you understand the magnitude of the problem, it only makes you humble,” says Kaçar.
Michael Marshall is a journalist and author of The Genesis Quest. He is based in Devon, UK
Article amended on 3 November 2023
We have clarified the full name and affiliation of Betül Kaçar
