Martin Rowson cartoon on the origins of life in deep sea vents

The origin of life is such a fabled event (more than 4 billion years ago) that searching for clues on the Earth today might seem a fool’s errand. But, piece by piece, a wonderfully interlocking skein of evidence is emerging. It began with a chance encounter in the deep ocean.

In 1977, the deep-sea submersible research vessel Alvin discovered hot upwelling mineral vents – black smokers – in the deep Pacific Ocean, off the coast of California. Such upwellings occur near the boundaries of the Earth’s tectonic plates where there is volcanic activity. The streams that pour out are hot water laced with minerals that then accumulate and grow into rocky towers. The interest of biologists and biochemists was piqued by the constant flow of hot, chemically rich effluents, which suggested that this might be life’s birthplace.

The energetic chemistry discovered in the black smokers bore some resemblance to the energy metabolism of modern cells, especially in the presence of iron-sulphur clusters. These clusters lie at the heart of many of life’s nanomachines – large protein complexes, often with moving parts – that perform life’s key functions (see my article “Nature’s Nanomachines” in the Spring 2021 edition of New Humanist).

Black smokers proved to be a dead end: they were too hot and unstable to have been a source of early life. However, the idea that deep sea vents might point to the secret of the origin of life was taken up by other researchers.

In 1988, the geochemist Mike Russell, at Glasgow University, predicted the existence of another kind of hydrothermal vent: alkaline, and much cooler. This vent, he hypothesised, could have used hydrogen spewing from the effluents to react with dissolved carbon dioxide (CO2) in the ocean waters, creating the precursor chemicals of life. In fact, Russell made the claim: “The purpose of life is to hydrogenate carbon dioxide”.

This may sound grandiose – but as it turned out, Russell was correct. In December 2000, mysterious white chimney structures, now dubbed the Lost City, were found by chance by the same submersible vessel on the mid-Atlantic seafloor. (The very best science is done like this: a prediction – often seemingly improbable – followed by the clinching discovery.)

The most exciting revelation of the calcium carbonate chimneys, which are up to 60m tall, was their porous structure. Each has many tiny holes like a mineralised sponge, through which, as Russell predicted, alkaline fluids rich in hydrogen and minerals really do pour into an acidic ocean which contains dissolved CO2 (the ocean is mildly acidic now, but it was much more so 4 billion years ago). In primeval conditions, these vents could have spawned and harboured the necessary ingredients and the right conditions to promote the growth of biomass. It seems that we might have finally found the birthplace of life on Earth.

"Life is a river that never stalls"

Over the last two decades, much work has been done on deep-sea vents. There is a striking similarity between their chemistry and the biochemistry of primitive bacteria which still exist today and can live on purely chemical substances. As a result, we now have a detailed and highly plausible account of how life probably arose. These are exciting times, but the science is complex and difficult to explain to the general public.

Thankfully, one of the researchers working on the origin of life is also an excellent communicator. Nick Lane, professor of evolutionary biochemistry at University College London, has been working on the question of what life is, and how it began, for more than a decade. Most biologists see life in terms of information encoded by DNA, but Lane focuses on the flow of energy through living things. In his latest book, Transformer, which came out in May 2022, he writes that his aim is to “explain how the flow of energy and matter structures the evolution of life and even genetic information. I want to turn the standard view upside down.”

An analogy for Lane’s view of life can be found in rivers. A river is only a river if it is in motion, and that motion requires energy. Rivers are not only water, just as living things are not only the chemicals that comprise them. In every living cell, chemical matter is incessantly in motion to a frantic degree. Humans die very quickly if oxygen is withdrawn, but what kills us is not suffocation but a collapse of the energy flow through every cell.
Living things need fuel to power the metabolism of life. They get this by trading gases with the environment: for plants in today’s world, that means CO2 in, oxygen out, and the reverse for animals. Life is reproduced through DNA. But the puzzle has always been to discover how primitive chemistry could have led to intricate biochemistry in the first place. Darwin memorably mused on the subject of the origin of life:

“But if (and oh what a big if) we could conceive in some warm little pond with all sorts of ammonia and phosphoric salts, light, heat, electricity etcetera present, that a protein compound was chemically formed, ready to undergo still more complex changes.”

This seemed unlikely, because in open water any interesting chemistry would quickly be dispersed – a drop in the ocean is more than a metaphor here. However, we can now hypothesise that this is where the deep-sea vents came into play. They could have provided a shelter in their pores in which useful molecules could accumulate in the unceasing flow. Over millions of years, the constancy of the same upwellings satisfies the “life is a river that never stalls” requirement.

But what on the primeval Earth could have enabled the vital reaction between CO2 and hydrogen? This is the problem that Lane’s lab and others have been working on. In 2020, a research team led by Lane’s former student Victor Sojo, with Reuben Hudson, managed to mimic conditions in the primordial vents. They demonstrated that an energy gradient that exists in the vents between the alkaline effluents and the acid ocean was indeed capable of hydrogenating CO2. Other labs are producing similar results, confirming what was long suspected but difficult to prove. Lane says: “I take my hat off to them”.

The beginning of natural selection

If the first requirement of life is the hydrogenation of CO2, what is needed next? All life today is composed of cells and new life can now only come into being through the division of living cells. Cells are cells because they are bounded by a membrane – a barrier between the non-living outside world and the living interior (or between one cell and another).

Cell membranes are made from fatty acids which behave like detergents in that one end of the molecule is water repellent and one end is water loving. In the reactions that occur in the vents, long-chain fatty acids would have formed easily. It’s a simple lab demonstration to show that these fatty acids will self-assemble into bilayer spheres in water, with the fatty ends butting together, separating the watery world inside from the watery world outside.

So the idea is that the pores in the chimneys were a template for protocells with this bilayer structure. This was the beginning of the metabolism that powers all cells today. The minerals that pour out of the vents have catalytic properties and would have created a positive feedback loop in which the protocells that could fix more carbon would come to dominate the vents. This was the beginning of natural selection.

In Transformer, Lane demonstrates the centrality of this metabolism to all life in a suite of reactions that goes by the name of the Krebs Cycle, after the great biochemist Hans Krebs (1900-1981). The textbook Krebs Cycle describes oxygen “burning” glucose to provide energy and to create the basic biomass of life, whilst emitting CO2 in the process. It is at the heart of the way that animals like us live and move and exist. Ironically, Lane’s first encounter with learning about the cycle was unpropitious. “I did biology and chemistry at school and loved them both and thought that combination was perfect but I did biochemistry at university and hated it,” he told me, “hated it because I was told to memorise pathways off by heart.”

It turned out that this rote learning was not only tedious and unhelpful. It also sold the Krebs Cycle short. The cycle had already been revealed, back in 1966, to be more complicated than the textbook version. It was capable of working backwards, starting with CO2 and creating biomass from the products of that first reaction with hydrogen. As is often the way, however, this concept was resisted by the research community for more than 20 years.

The reverse Krebs Cycle is now fully recognised and is vital to the hypothesis that life may have emerged from the deep-sea vents, long before the existence of DNA or its cousin RNA.

This is highly promising, but as Lane himself admits in Transformer, “many a beautiful idea has been killed by ugly facts”. The search for life’s greatest prizes has always been tortuous, but many teams of researchers are working to confirm Lane’s ideas experimentally. He makes sure, in the book, to fully acknowledge the work of his PhD students and post-doctoral researchers. Great strides are being made, but more hard evidence is needed.

The overriding idea of the vent hypothesis is that the chemistry that existed in the pores of the vents was eventually interiorised by the protocells that nestled within them. In a thrilling recent experiment in Lane’s lab, Sean Jordan and Hanadi Rammu discovered that protocells form particularly readily in simulated vent conditions. The amino acid cysteine, mixed with iron and sulphides found in the vents, produced exactly the kind of iron-sulphur clusters at the heart of modern protein enzymes.

Did the origins of life involve DNA?

One area of research is revealing how the deep-sea vents might have produced the molecule ATP (adenosine triphosphate), the universal fuel of life, powering every move we make and every internal process in all living things. Lane’s PhD researcher Silvana Pinna is investigating how this vital molecule might have originated in the hydrothermal vents.

In the very early stages of the vents, the chemicals formed would have been tiny molecules with only a handful of atoms. Life in its developed form uses giant molecules – long chains wound into a double helix in DNA or folded into intricate structures in proteins. Pinna has shown that the simple molecule acetyl phosphate can catalyse the formation of ATP from ADP (adenosine diphosphate) and that this reaction is chemically favoured under hydrothermal conditions. The paper by Pinna and her colleagues, recently published by the journal PLOS Biology, concludes:

“This implies that ATP could have become the universal energy currency of life not as the endpoint of genetic selection or as a frozen accident, but for fundamental chemical reasons.”

Other researchers, such as Markus Ralser, the Einstein professor of biochemistry at the Einstein Foundation in Berlin, are producing similar results in finding purely chemical routes to the basic building blocks of life. Lane told me: “What’s great about Markus’s work is that he’s brought attention to something that he calls the ‘end product problem’.” This poses the apparently awkward fact that the intermediate stages of the Krebs cycle only make sense when they are all in place. Both Ralser’s and Lane’s labs have found that Krebs and other key intermediates occur in sequence by simple chemistry alone, as opposed to the chemistry that can only be performed in living things today by the complex protein enzymes in every living cell.

Such chemistry, with that river metaphor in mind, is as natural as water flowing downstream. It’s the chemistry of reactions that happen by necessity, as when hydrogen reacts with oxygen to form water, or sodium with chlorine to form sodium chloride. The success of work like this leads Lane to suggest: “I’m coming to believe that the whole of biochemistry up to nucleotide synthesis just happens spontaneously . . . It’s just built into the chemistry of CO2”.

This is a remarkable conclusion, overturning the generally held assumption that the origin of life must have had something to do with DNA or its cousin RNA.

"Tornado in the junkyard"

Life originating by purely chemical means was once considered so far-fetched that the astronomer Fred Hoyle compared it, in 1983, to “the chance that a tornado sweeping through a junkyard might assemble a Boeing 747”. But it seems that the currents that flow though the hydrothermal vents really are the “tornado in the junkyard”, able to create some of life’s early metabolism.

This theory could also solve the problem of how DNA originated. Today, new life is produced by coding from DNA, but a code can’t predate the thing coded for. How did it emerge in the first place? The genetic code by which DNA spells out the composition of proteins is regarded by some as a frozen accident – there seems no rhyme or reason to it, like the Morse code, which could just as well have a completely different pattern of dots and dashes. But a recent paper published in the journal Biochimica et Biophysica Acta – Bioenergetics by Lane’s PhD students – Stuart Harrison, Raquel Nunes Palmeira and Aaron Halpern – shows how the genetic code most likely evolved.

They have discovered that the nucleotide bases that form DNA and its more primordial cousin RNA actually have a direct chemical affinity for particular amino acids, the building blocks of proteins. The early little strings of nucleotides – forerunners of the great chains of RNA and DNA – had no coding function: in the first instance, they were catalysts, just like the iron-sulphur clusters before them and the protein enzymes that succeeded them. But then, depending on their position in the reverse Krebs cycle, particular amino acids became associated with one or other of the four RNA bases.

The authors of the paper conclude by noting that coding – biological information encoded in genes – thus emerged by chemical necessity. The genetic code wasn’t imposed on life, but evolved alongside it. The theory “offers a framework that enables the transition from deterministic chemistry to genetic information at the origin of life” [my italics]. This is a conclusion as dramatic as that of Watson and Crick’s iconic 1953 paper, in which they posited that DNA was the means through which life was reproduced.

Since the discovery of DNA, inquiries into the origin of life have tended to focus on how DNA replication and the genetic code originated. How could complex life have begun to develop without such a code? We may now be opening a new chapter in biology that turns our assumptions upside down. The work of Lane and his colleagues shows that the complex lifeforms that exist on Earth today may have evolved from simple beginnings. The systems that power these lifeforms may seem bafflingly sophisticated, but they could have evolved by purely chemical means. Now, we see how, from the ever-pulsing currents on the primeval ocean floor, life could have booted itself up.

This piece is from the New Humanist winter 2022 edition. Subscribe here.