Authors: Adam Rutherford
It's thought that these bobble-headed phospholipid molecules would not have been difficult to find on the early earth, not because we have traces of them, but because they're easy to make with different recipes. One of the most striking is in experiments that blast icy fragments resembling the composition of comets with ultraviolet light to mimic an interstellar forge. But they've also been found in meteorites, and made with much more Earth-bound reactions. As far as ingredients go, there is ample sufficiency, and they make a good contender for the first membrane. But as the origin of life was chemistry transitioning to biology, these prototype membranes need to acquire complexity from their simple, self-organizing origin.
The membranes of modern cells need to be sophisticated to prevent leakiness. A free flow of immigration into a cell can cause all sorts of turmoil and unrest; similarly, accidentally spilling your most prized secrets and possessions is a dangerous game. So the custom weigh stations on the modern membrane preside over a careful coordination that will expel molecules (for messaging or as waste) and let the right ones in. It is not enough to say that the complex system we see now is simply better than what came before. In order to uncover the real transition, you have to show why one is preferential to the other. In evolution, things are never frozen and rarely accidents. So why would a complex system take over from a simpler one? Itay Budin and Jack Szostak experimentally asked that question of their protocells. The answer seems to come from that most Darwinian of concepts: competition.
For natural selection to play out its hand, variation is needed. If everyone was the same, not only would it be quite boring, there would be no potential foothold for advantage. Getting one up on your siblings is what that variety produces if you are lucky enough to bear a competitive advantage. It could be for sunlight, food, or a mate, but without competition there is no change. Even though Darwin didn't deal with the origin of life other than idly speculating on it. Not for the first time, we see a Darwinian process playing out in experiments that are most certainly prelife. The variation added to the stable mix of simple protocells in Budin and Szostak's experiment was the addition of minute quantities of complex phospholipids more like the ones in modern cells. They nestle into the membrane and sit quite comfortably next to their single-tailed colleagues. However, those protocells grow one-sixth larger than their simple brethren. A cell that acquired the ability to make these phospholipids would therefore immediately grow larger than one that could not. The increased size also encourages cell division.
Szostak's experiments, by his own admission, are a long way from replicating the spontaneous formation of anything as sophisticated as the contemporary cell membrane. There are all sorts of caveats to assuming that this is the re-creation of what happened the first time around. The phospholipids need to be made somehow, as they are not abundant on Earth or in the heavens in the way that their single-tailed cousins are. That requires at least the most basic form of metabolism, which speculatively, in an early biochemistry, might be supplied by mechanisms hitherto undiscovered. On top of that, the winning cells, with their modern phospholipid membranes, lose their ability to let molecules inside and out as they please. That demands the emergence of the channels and pores which make the modern cell membrane a custom house, rather than merely a port. Protocells are apparitions of cells and do cell-like things. The simplicity of their formation is great solace for those who find the spontaneous emergence of all the facets of cellular life a big ask. Containment of living processes is necessary but not sufficient to enable life as we know it, though these experiments suggest a pathway. Nevertheless, the spontaneous formation of protocells in a dish is a simple yet significant step in re-creating genesis.
Protocells also mimic cell division. In us, the process of a cell splitting in two is a highly orchestrated and active maneuver that requires metabolic energy. Not only does the DNA in its entirety have to be copied, it has to be arranged for the physical split, and the membrane has to grow big enough to make two cells from one. Modern cells have a network of internal struts and scaffolding that helps everything into its right place so the split happens evenly. At the beginning of cellular life, there was presumably no such architecture. Szostak's work also demonstrates that physical properties force cell division, as simple as squeezing the protocells through the pore in a filter. So again, as with the experiments that show how ribozymes might have once been the original code, the formation of the cell membrane is a lot less mysterious, thanks to these experiments that show how something sophisticated might have emerged spontaneously from something simpler.
Deep, Hot Water
In living cells, DNA and membranesâthe information and packaging that sustain life's great descentâall require energy. The emergence of membranes and code can happen in a variety of locations if the ingredients and conditions are right, but if we accept that underlying these chemistries, life is a process of harnessing energy from the environment, a very different real-world scenario is required.
On a gray bench, on the first floor of a building in which Charles Darwin once lived, is a glass jar. It's about big enough to fit a human head inside. It is perched on a wide-legged tripod, and a tinfoil-insulated rubber hose is piped into its base, where near-boiling water rushes in. On one side of the jar, cold water flows in through two glass nozzles. The top of the jar is a heavy glass lid held in place with bolts and a thick rubber seal.
This is a bioreactor, which may sound fancy, but in fact is rather old-fashioned, like something drawn by the British cartoonist and illustrator William Heath Robinson. The laboratory itself, in the aptly named Darwin Building on Gower Street in central London, is filled with University College London's phalanx of evolutionary biologists and is a typical contemporary working hive of molecular biology with benchtop spinners, shakers, machines, and countless tiny tubes of colorless liquids. The bioreactor jar sits atop its tripod sprouting wires, tubes, and foil, looking somewhat ectopic in its otherwise hi-tech, sleek surroundings.
The magic touch is what is in the jar. About the size of a brick of uncut Stilton is a block of what looks like gray stone. In fact, it's a ceramic, carefully designed to mirror the mineral growths that poke out of a newly discovered breed of submarine hydrothermal vent. It looks like a cross between a sponge and pumice. In fact, UCL's Nick Lane, who designed this rig, experimented with both of these when trying to generate the right amount of flow-through around the material. In baking this block of sophisticated clay foam, the bubbles and pores were delicately controlled to create just the right conditions to emulate the underwater bubbling vents that Lane believes are the best candidate for the site of the first life.
The word
vent
suggests vertical chimneys, as seen in the breathtaking images of the teetering towers of the Lost City way down at the bottom of the Atlantis Massif, halfway between the Canary Islands and Bermuda. Pictures and the description of this underwater metropolis were first published at the beginning of the twenty-first century, a new type of seabed hydrothermal field, fizzing with the energy of reactions between the mantle rocks and seawater. And despite heat of up to 194 degrees Fahrenheit and highly alkaline waters, these towers are teeming with life, so much so that lead scientist Deborah Kelley from the University of Washington in Seattle told
Nature
in 2001, “You can't even see the rock because of the amount of bacteria.”
It's these vents, ever changing through the continuous effervescence from the active earth below, that Nick Lane's ceramic is modeling. The vents emerge from the seafloor as the plates of the earth shift and split, revealing fresh hot virgin rock drawn up from the mantle. Once exposed, they react with seawater, splitting it apart into oxygen and hydrogen and a host of other gasses that are equally brimming with energetic potential, eager to react. In so doing, these gasses percolate through the rocks, driving a honeycomb into them as they cool in the surrounding seawater, a process called serpentinization. It's in these tiny hatcheries that Nick Lane, Bill Martin, Mike Russell (at NASA's Jet Propulsion Lab at Caltech in California), and a small handful of other scientists think the first living processes occurred, before RNA, DNA, and cell membranes. In the lab, the flow of water and gasses around the porous ceramic is not simply from bottom to top, but continuously circulating in and out of tiny pores, just as it does in the Lost City.
A modern cell's energy currency comes in the form of a molecule called ATP. It is a molecule that is constantly being made and recycled, as it holds energy in its chemical bonds that cells can use, to the extent that each day you will make and use your own body weight in ATP. The process by which this happens is a complex metabolic cycle that relies on there being a gradient of electrically charged hydrogen atoms (protons) across a membrane, a maintained imbalance. In our cells, that power generation happens in the mitochondria (the powerhouses of complex life) and in bacteria and archae, in membranes just inside cell walls. Special proteins on these membranes act like turbines, and the flow of protons through these turbines results in the energy being generated, which gets stored in ATP, which is used to power all the processes of the cell. This cycle is so fundamental to so many living processes that it seems like a good contender for the most elemental metabolism life can have, and therefore a system that could underlie all life. It relies simply upon there being more protons on one side of a membrane than the other.
This is why Mike Russell has driven the idea that the hydrothermal vents of the Lost City offer up a model for the nursery of first life. Due to the precise qualities of the chemicals bubbling up from the reactions between the rocks and the sea, they form natural proton gradients in the swirls around the honeycomb rocks. In our cells, that proton gradient is maintained by our biochemistry, and it is the maintenance of that imbalance that keeps us from drifting toward decay.
The heat of the vents is not what is important: we don't use heat to generate our energy, nor, indeed, a bolt of lightning as Stanley Miller's experiment did, so why would first life? Cells harness chemical energy in many forms, with almost inscrutable metabolic pathways, but with ATP produced by the flow of a proton gradient at its core. These are systems that are far from equilibrium, and just like life, a continuous restriction of an unfettered increase in entropy.
In a sense, the bubbling vents are a mixture of the right ingredients in such a way that biology can emerge from chemistry, but it is a far cry from the spontaneous generation of a primordial soup. In the vents it's the circulating gasses flowing out that maintain the thermodynamic imbalance. Specifically, protons stream around the pockets in the rocks, to be concentrated into the alkaline interior away from the acid sea. At the bottom of the Atlantic Ocean is a bubbling bioreactor with a thermodynamic imbalance of streaming protons preventing retirement to equilibrium. The metal nuggets studded in the rocks catalyze the whole process, and the empty cells of the porous rock concentrate the ingredients in this never-resting mix.
As a site for the origin of life, hot vents fit seductively well, and Nick Lane's bioreactor is one of very few experiments to test that idea. It is ongoing, and at the time of this writing results are unknown. If successful, Lane hopes to see the emergence of reactions and chemicals that are similar to or the same as the ones we see in biology. This might then suggest a place for Luca's birth.
But Bill Martin pushes the model even further. To him, Luca is something that is not a free-living cell at all.
7
Even with a bushy network between single cells that populated the earth for two billion years, Luca still stands as a common ancestor of both archaea and bacteria. In Martin's version, Luca was a swill of activity, but not a free-living cell as we might have assumed. The beginnings of life were not inside a membrane-bound cell at all. Instead, the last common ancestor of the two oldest domains of life was locked inside the rocky shell of the alkaline underwater vents. In there, concentrated and protected, but fed and with a constant supply of charged atoms, is the transition from chemistry to biochemistry, and then on to life. The evolutionary split that wrenches archaea from bacteria happens after the RNA world has given way to DNA, but before the arrangement of fatty molecules into the cell membrane. They have the same genetic code, and they both rely on ribosomes as their protein factories. In both, they are more similar to each other than to our cells. But in archaea, the tools for writing and copying RNAâa protein called RNA polymeraseâare more similar to our own than they are to bacteria's. The archaea's outermost shell, the cell wall, is different from a typical bacterial cell wall, and the membrane is radically different from anything else. These differences are present in contemporary species, but they are fundamental enough to have roots beneath the bottom of the intertwined bushy bit of the tree of life. According to Martin, first life was housed not in membranes, but in rock.
Martin's model starts with bubbling hydrogen, ammonia, and hydrogen sulfide frothing around the pores in a serpentinized rock. These pockets look rather like the empty cork chambers that Robert Hooke saw with his microscope at the very beginning of this journeyânot cells as we know them, but cells like the honeycomb cavities of a beehive. The acid sea and the alkali interior of the vent rocks provide a natural proton gradient for the flow of power that incepts a basic form of metabolism, and it is continuous for as long as the vent is active. Simple biochemical reactions that we observe in modern cells begin to occur in this energetic mix, and we start to see amino acids being forged in this tumult. Next come other foundation biomolecules, such as sugars, purine, and pyramidine rings, and other molecules that we see in metabolic cycles. Purine and pyramidine go on to fuse, becoming basesâthe letters of genetic code, maybe as they do in John Sutherland's syntheses. When these letters link, the RNA world can begin, only to be eventually replaced by DNA with its superior data-storage prowess. But it's all still trapped in the tortuous labyrinths of the rock, the pores concentrating biochemical action, rather than the dilution of a warm pond of a broth. This locked reactor is the last common ancestor of everything, rock-bound for now, but soon acquiring the skin that will allow it to break free.