The Origin of Life: Home and Dry

From New Scientist - 28 April 2016

THE ORIGIN OF LIFE

Home and dry

Water was probably the last thing the first life needed, says Colin Barras

"SOME warm little pond." Charles Darwin's speculative description of life's cradle, in a letter written to the botanist Joseph Hooker in 1871, still chimes today. Seed a watery environment with the right ingredients, Darwin mused, then cosset it with a little light, heat or electricity, and a purely chemical miracle of creation might occur.

Hard and fast evidence of how and where on Earth inanimate matter became animate is hard to come by. Other backdrops for life's first steps have gained in popularity since Darwin's time – around submarine hydrothermal vents, in ice or on Earth's radioactive first beaches, for example. If pressed, though, most of us would still plump for the primordial soup.

In the intervening years, we have devised more detailed recipes showing how the early Earth might have cooked up simple organic molecules, and how these might have reacted further to form the more complex building blocks of life: things like amino acids, DNA and RNA. Besides the right chemical ingredients, the process needs warmth, sunlight, perhaps a little lightning and, most importantly, H2O. Water is, after all, the essential solvent that underpins carbon-based life.

For Steven Benner, that is all a fairy tale. "We tend to think that water's properties are ideal for life, but the opposite is true," he says. "Water is corrosive." Benner is a chemist at the Foundation for Applied Molecular Evolution in Florida and for three decades he has been doing pioneering work in synthetic biology, which aims to recreate life's chemistry in the test tube. And he is no lone voice. As water's deleterious effects have become more apparent, many researchers are asking: is it time to dry out life's recipe?

Around 70 per cent of our planet's surface is ocean, and water makes up 60 per cent of our body weight. Few living things can survive for long without water: it is a perfect medium in which organic molecules can dissolve and react to sustain the core processes of life on Earth.

But this perfect solution is also a problem. Life's molecules don't just dissolve in water; the electron-rich oxygen of its molecules attacks them, and they begin to fall apart. "In your body right now, the DNA in your cells is losing an amino group many times a second because of the action of water," says Benner. Living things keep their molecules intact only through clever chemical strategies that perpetually repair the breakages.

Tricky when wet

The first life on Earth wouldn't have had time to develop those strategies. According to the widely accepted "RNA world" theory, RNA was the first self-replicating molecule, and a precursor to today's DNA-based life (see "Dawn of the living"). Like DNA, RNA is built up from nucleotides, complex organic molecules that are themselves formed from two simpler components, a nucleobase and a sugar called ribose. Decades of research have shown that making nucleotides in water is a very tricky business. Individual steps can be made to work, but they don't all gel together. "We are still at the stage of scraping out the product of step seven, and carefully spooning it into the flask to begin step eight," says Benner. Fail to spoon in just the right amounts of various molecules at the right time, and the end result is a gunky mess.

In 2004, Benner made a breakthrough. He showed that borates – minerals containing varying proportions of boron and oxygen – could act as scaffolds for the construction of ribose, making that part of the chemistry a much more hands-off, naturally plausible process. The problem of attaching the ribose to the nucleobases remained, however, until in 2012 Benner made a simple and bold suggestion: to make life, just remove water. By replacing it with an organic solvent richer in carbon and poorer in oxygen such as formamide (CH3NO), the right components would, in theory at least, stick together spontaneously to make RNA. This idea was bolstered by seminal work in 2015 showing that a simple set of chemical reactions can yield all the important building blocks of life, but only when the conditions are dry or nearly dry for some stages of the reaction.

Formamide would have been created when hydrogen cyanide in Earth's early atmosphere mixed with water. Its boiling point is higher than that of water, so in a hot environment the formamide would have become more concentrated as the water evaporated away.

Borates are scattered across Earth's surface today, where they result mainly from the erosion of igneous rocks. Looking at Earth now, Benner has found one environment that combines both sweltering conditions and the presence of borates. It aptly sums up how unexpected life's earliest requirements might have been. Its cradle, says Benner, might have looked a lot like California's Death Valley.

Benner's chemistry arguably provides the first one-pot recipe for life that can bubble away without human intervention. Armen Mulkidjanian, a chemist at the University of Osnabrück in Germany, is a fan. But he points to a problem with cooking it up in a primeval Death Valley. "The world's borate minerals are all found in relatively young rocks," he says. There is no evidence that surface concentrations of borates were sufficient for the chemistry to work until about 3 billion years ago, he says – around a billion years after life supposedly got started.

So where then? Mulkidjanian sees inspiration in the geothermal fields of Kamchatka in eastern Russia. These are spots where fluids have flowed through Earth's crust and come to the surface as vapours, bringing with them nutrients accumulated from rocks along the way. Borates are often found in these geothermal fumes, as are the chemical components of formamide. One further chemical convergence emboldens Mulkidjanian in thinking that a similar environment could have cradled life: the geothermal fields of Kamchatka are just about the only place on Earth where the balance of sodium and potassium ions matches that inside living cells.

Mulkidjanian's twist on Benner's tale has gained supporters. "What's nice is that geothermal fields provide a constant set of conditions for the origin of life, since the chemistry is coming from Earth's stable interior and not its exterior," says Ernesto Di Mauro at the Sapienza University of Rome, Italy. "If you frame Benner's proposal in these geothermal fields, you have a scenario that doesn't have many weak points."

But not so fast. These scenarios require Earth to have supplied dry environments like a Death Valley or a Kamchatkan geothermal field 4 billion years ago. Until recently, the consensus would have been that this was no problem: Earth was then exiting an interval dubbed the Hadean because of its hot and hellish conditions. But in the past decade, geologists have cooled on the idea of a hot young Earth. Their main evidence comes from tiny crystals, each less than a millimetre across, of a mineral called zircon. These are tough, easily outlasting the rocks they formed in, which have been obliterated by subsequent tectonic activity.

A close look indicates that the crystals were made in cool, soggy conditions, implying that Earth's early history was wet, with land accounting for perhaps just 5 or 10 per cent of its surface. Joseph Kirschvink, a planetary scientist at the California Institute of Technology in Pasadena, goes so far as to speculate there was no dry land at all. That leads him to a seemingly way-out conclusion: if the first life needed to be dry, it cannot possibly have started on

Earth.

Premature requiem

The search for life beyond our planet has also traditionally followed the mantra "follow the water" – although recent discoveries in and out of the solar system are causing that assumption to be revisited (see "Worlds without water", below). Kirschvink has been an enthusiastic supporter of the idea that Earth's life possibly began on Mars, ever since the infamous announcement in 1996 that fossilised "microbes" had been discovered in a 4.1-billion-year-old Martian meteorite called ALH 84001. The consensus now is that these are just rock features that look like cells – but we should not discount the Martian option just on that basis, according to Kirschvink. "The requiem for life on Mars was very premature," he says.

And if life needed a dry place to get started, Mars had the right conditions at the right time. Although it once had an ocean basin around its north pole, its southern highlands were almost definitely never submerged. "The RNA world would have done very well there," says Kirschvink. He thinks that later on, probably after the RNA world had given rise to the DNA-based cellular life we are familiar with today, an asteroid hit the Martian surface, throwing chunks of rock and ice containing these cells beyond the planet's atmosphere. Perhaps as little as nine months later, some of them made it to Earth.

In 2013, at the Goldschmidt geochemistry conference in Florence, Italy, Benner agreed that there is logic to Kirschvink's arguments. "The evidence seems to be building that we are actually all Martians; that life started on Mars and came to Earth on a rock," he said, generating a wave of media interest.

Just weeks before the conference, James Stephenson, now at the NASA Ames Research Center, California, and his colleagues had provided further succour for the theory, with confirmation that Mars is rich in a key ingredient for Benner's pathway. They published an analysis of a 1.3 billion-year-old Martian meteorite called MIL 090030 that showed it was riddled with boron. "I was honestly surprised that people hadn't really looked at boron in Mars samples before," says Stephenson. He hopes to collaborate with Benner soon to develop the idea further.

Mulkidjanian agrees that conditions on early Mars may have been suitable for the origin of life, and wryly points to evidence that the planet may even have had geothermal fields similar to those in Kamchatka, his favoured sort of cradle for life.

But he questions whether dry life arriving on a wet Earth on a Martian meteorite could have assimilated well. Genomic studies show that life on our planet traces back to a collection of cells that survived by sharing the products of their genes, creating a single-celled organism referred to as the last universal common ancestor (see "Meet your maker"). "If you dropped a primitive Martian cell into Earth's oceans, it is highly unlikely that it would have proliferated alone," he says. Rather, it would take a whole microbial ecosystem arriving, intact, from Mars.

Back to Darwin

This hints at a wider problem. No matter where and on what planet the delicate early forms of life originated, water's corrosive nature would have caused them to struggle when first introduced to a wet environment. All indications are that this happened very early: life has thrived in the oceans for billions of years. "There is a paradox," admits Benner. "You have to get out of water to solve the water problem, but then you've got to get back into the water." The only real solution, he says, is to gradually moisten a dry cradle and allow the variety of molecules to either cope or perish through natural selection.

Or we tweak our story still further. Nicholas Hud, a chemist at the Georgia Institute of Technology in Atlanta, points out that most researchers accept that DNA somehow evolved from RNA, so we should at least consider the possibility that RNA evolved from a different molecule that was stable in water. "When I look at RNA, I see a molecule that is perfect at what it does, but that's hard to make," he says – perhaps a telltale sign that natural selection helped shape RNA. "Which is more probable? Life began on Mars, was transported to Earth and picked up where it left off, or life began on Earth, but with a molecule different from RNA?"

Hud's thinking could remove the need for Kirschvink's Martian scenarios and Benner's chemistry, but would demand a rethink of the underlying assumption that life's chemical origin lies with RNA. It would seem fitting, though, that the ultimate solution to the water problem, even before life as we know it got started, could lie in the principles of natural selection. Stories about the origins of life begin and end with Darwin.

Worlds without water

Evidence that drinkable water once flowed on Mars, as found by NASA's Opportunity rover, is still lapped up as suggesting the planet could have harboured life. But with the realisation that water may have hindered early life on Earth (see main story), should we be looking elsewhere?

In fact, astrobiologists at NASA and elsewhere have long discarded the assumption that life needs aqueous chemistry. Earth and Mars aside, the solar system body thought most likely to harbour life is Titan, Saturn's largest moon. The Cassini probe, in orbit around Saturn since 2004, has shown Titan's dense atmosphere veils rough terrain but also smooth seas filled not with water, but the hydrocarbons methane and ethane. "Titan is an excellent place to explore for non-aqueous experiments in chemical self-assembly," says Jonathan Lunine, a planetary scientist at Cornell University in Ithaca, New York.

Lab experiments confirm that amino acids, the basis of proteins, could be generated on the surface of Titan, although temperatures are so frigid – as low as -180 °C – that life there would probably not be able to operate on Earth-like chemical principles. Covalent bonds of the sort that underpin our carbon chemistry would not form and break quickly enough, but weaker van der Waals bonds would be more stable and could play a more prominent part.

Whether life's origins were wet, dry or something else altogether, the different sorts of chemistry that might support life mean we should keep an open mind when considering the 2000-odd planets that missions such as NASA's Kepler space telescope have now found orbiting other stars, very few of which look like Earth. "We cannot limit ourselves to what we know in exploring the unknown," says Lunine. "We cannot simply search for the keys to life's origins underneath the narrow beam of the aqueous street lamp."

Colin Barras

Origin of LIfe: Inevitable, Fluke or Both?

THE ORIGIN OF LIFE

Life: Inevitable, fluke or both?

In theory, life ought to arise wherever conditions are right. But that doesn't mean the universe is teeming with creatures like us, says Nick Lane

FOR four years, the Kepler space telescope scoured the sky for Earth-like planets around other stars. When its mission ended in August 2013, it had found so many that NASA came to a startling conclusion: our galaxy is teeming with planets capable of hosting life. There are perhaps 40 billion of them, 11 billion of which are small rocky worlds orbiting sunlike stars at a distance where liquid water may exist.

These discoveries are bringing an old paradox back into focus. As physicist Enrico Fermi asked in 1950, if there are many suitable homes for life out there and alien life forms are common, where are they all? More than half a century of searching for extraterrestrial intelligence has so far come up empty-handed.

Of course, the universe is a very big place. Even Frank Drake's famously optimistic "equation" for life's probability suggests that we will be lucky to stumble across intelligent aliens: they may be out there, but we'll never know it. That answer satisfies no one, however.

There are deeper explanations. Perhaps alien civilisations appear and disappear in a galactic blink of an eye, destroying themselves long before they become capable of colonising new planets. Or maybe life very rarely gets started even when conditions are perfect.

If we cannot answer these kinds of questions by looking out, might it be possible to get some clues by looking in? Life arose only once on Earth, and if a sample of one were all we had to go on, no grand conclusions could be drawn. But there is more than that. Looking at a vital ingredient for life – energy – suggests that simple life is common throughout the universe, but it does not inevitably evolve into more complex forms such as animals. I might be wrong, but if I'm right, the immense delay between life first appearing on Earth and the emergence of complex life points to another, very different explanation for why we have yet to discover aliens.

Living things consume an extraordinary amount of energy, just to go on living. The food we eat gets turned into the fuel that powers all living cells, called ATP. This fuel is continually recycled: over the course of a day, humans each churn through 70 to 100 kilograms of the stuff. This huge quantity of fuel is made by enzymes, biological catalysts fine-tuned over aeons to extract every last joule of usable energy from reactions.

The enzymes that powered the first life cannot have been as efficient, and the first cells must have needed a lot more energy to grow and divide – probably thousands or millions of times as much energy as modern cells. The same must be true throughout the universe.

This phenomenal energy requirement is often left out of considerations of life's origin. What could the primordial energy source have been here on Earth? Old ideas of lightning or ultraviolet radiation just don't pass muster. Aside from the fact that no living cells obtain their energy this way, there is nothing to focus the energy in one place. The first life could not go looking for energy, so it must have arisen where energy was plentiful.

Today, most life ultimately gets its energy from the sun via photosynthesis by plants. But photosynthesis is an enormously complex process and probably didn't power the first life. So what did?

Reconstructing the history of life by comparing the genomes of simple cells is fraught with problems. Nevertheless, such studies all point in the same direction. The earliest cells seem to have gained their energy and carbon from the gases hydrogen and carbon dioxide. The reaction of H2 with CO2 produces organic molecules directly, and releases energy. That is important, because it is not enough to form simple molecules: it takes buckets of energy to join them up into the long chains that are the building blocks of life.

A second clue to how the first life got its energy comes from the energy-harvesting mechanism found in all known life forms. This mechanism was so unexpected that there were two decades of heated altercations after it was proposed by British biochemist Peter Mitchell in 1961.

Universal force field

Mitchell suggested that cells are powered not by chemical reactions, but by a kind of electricity, specifically by a difference in the concentration of protons (the charged nuclei of hydrogen atoms) across a membrane. Because protons have a positive charge, the concentration difference produces an electrical potential difference between the two sides of the membrane of about 150 millivolts. It might not sound like much, but because it operates over only 5 millionths of a millimetre, the field strength over that tiny distance is enormous, around 30 million volts per metre. That's equivalent to a bolt of lightning.

Mitchell called this electrical driving force the proton-motive force. It sounds like a term from Star Wars, and that's not inappropriate. Essentially, all cells are powered by a force field as universal to life on Earth as the genetic code. This tremendous electrical potential can be tapped directly, to drive the motion of flagella, for instance, or harnessed to make the energy-rich fuel ATP.

However, the way in which this force field is generated and tapped is extremely complex. The enzyme that makes ATP is a rotating motor powered by the inward flow of protons. Another protein that helps to generate the membrane potential, NADH dehydrogenase, is like a steam engine, with a moving piston for pumping out protons. These amazing nanoscopic machines must be the product of prolonged natural selection. They could not have powered life from the beginning, which leaves us with a paradox.

Life guzzles energy, and inefficient primordial cells must have required much more energy, not less. These vast amounts of energy are most likely to have derived from a proton gradient, because the universality of this mechanism means it evolved early on. But how did early life manage something that today requires very sophisticated machinery?

There is a simple way to get huge amounts of energy this way. What's more, the context makes me think that it really wasn't that difficult for life to arise in the first place.

The answer I favour was proposed 20 years ago by the geologist Michael Russell, now at NASA's Jet Propulsion Laboratory in Pasadena, California, who had been studying deep-sea hydrothermal vents. Say "deep-sea vent" and many people think of dramatic black smokers surrounded by giant tube worms. Russell had something much more modest in mind: alkaline hydrothermal vents. These are not volcanic at all, and don't smoke. They are formed as seawater percolates down into the electron-dense rocks found in the Earth's mantle, such as the iron-magnesium mineral olivine.

Olivine and water react to form serpentinite in a process that expands and cracks the rock, allowing in more water and perpetuating the reaction. Serpentinisation produces alkaline fluids rich in hydrogen gas, and the heat it releases drives these fluids back up to the ocean floor. When they come into contact with cooler ocean waters, the minerals precipitate out, forming towering vents up to 60 metres tall. Such vents, Russell realised, provide everything needed to incubate life. Or rather they did, 4 billion years ago.

Back then, there was very little, if any, oxygen, so the oceans were rich in dissolved iron. There was probably a lot more CO2 than there is today, which meant that the oceans were mildly acidic – that is, they had an excess of protons.

Just think what happens in a situation like this. Inside the porous vents, there are tiny, interconnected cell-like spaces enclosed by flimsy mineral walls. These walls contain the same catalysts – notably various iron, nickel and molybdenum sulphides – used by cells today (albeit embedded in proteins) to catalyse the conversion of CO2 into organic molecules.

Fluids rich in hydrogen percolate through this labyrinth of catalytic micropores. Normally, it is hard to get CO2 and H2 to react: efforts to capture CO2 to reduce global warming face exactly this problem. Catalysts alone may not be enough. But living cells don't capture carbon using catalysts alone – they use proton gradients to drive the reaction. And between a vent's alkaline fluids and acidic water there is a natural proton gradient.

Could this natural proton-motive force have driven the formation of organic molecules? I'm working on exactly that question. It is too early to say for sure, but the early signs are that the answer is yes.

What would that solve? A great deal. Once the barrier to the reaction between CO2 and H2 is down, the reaction can proceed apace. Remarkably, under conditions typical of alkaline hydrothermal vents, the combining of H2 and CO2 to produce the molecules found in living cells – amino acids, lipids, sugars and nucleobases – actually releases energy.

That means that far from being some mysterious exception to the second law of thermodynamics, from this point of view, life is in fact driven by it. It is an inevitable consequence of a planetary imbalance, in which electron-rich rocks are separated from electron-poor, acidic oceans by a thin crust, perforated by vent systems that focus this electrochemical driving force into cell-like systems. The planet can be seen as a giant battery; the cell is a tiny battery built on basically the same principles.

I'm the first to admit that there are many gaps to fill in, many steps between an electrochemical reactor that produces organic molecules and a living, breathing cell. But consider the bigger picture for a moment. The origin of life needs a very short shopping list: rock, water and CO2.

Water and olivine are among the most abundant substances in the universe. Many planetary atmospheres in the solar system are rich in CO2, suggesting that it is common too. Serpentinisation is a spontaneous reaction, and should happen on a large scale on any wet, rocky planet. From this perspective, the universe should be teeming with simple cells – life may indeed be inevitable whenever the conditions are right. It's hardly surprising that life on Earth seems to have begun almost as soon as it could.

Then what happens? It is generally assumed that once simple life has emerged, it gradually evolves into more complex forms, given the right conditions. But that's not what happened on Earth. After simple cells first appeared, there was an extraordinarily long delay – nearly half the lifetime of the planet – before complex ones evolved. What's more, simple cells gave rise to complex ones just once in 4 billion years of evolution: a shockingly rare anomaly, suggestive of a freak accident.

If simple cells had slowly evolved into more complex ones over billions of years, all kinds of intermediate cells would have existed and some still should. But there are none. Instead, there is a great gulf. On the one hand, there are the prokaryotes (bacteria and archaea), tiny in both their cell volume and genome size. They are streamlined by selection, pared down to a minimum: fighter jets among cells. On the other, there are the vast and unwieldy eukaryotic cells, more like aircraft carriers than fighter jets. A typical single-celled eukaryote is about 15,000 times larger than a bacterium, with a genome to match.

All the complex life on Earth – animals, plants, fungi and so on – are eukaryotes, and they all evolved from the same ancestor. So without the one-off event that produced the ancestor of eukaryotic cells, there would have been no plants and fish, no dinosaurs and apes. Simple cells just don't have the right cellular architecture to evolve into more complex forms.

Why not? I recently explored this issue with the pioneering cell biologist Bill Martin of the University of Düsseldorf, Germany. Drawing on data about the metabolic rates and genome sizes of various cells, we calculated how much energy would be available to simple cells as they grew bigger.

What we discovered is that there is an extraordinary energetic penalty for growing larger. If you were to expand a bacterium up to eukaryotic proportions, it would have tens of thousands of times less energy available per gene than an equivalent eukaryote. And cells need lots of energy per gene, because making a protein from a gene is an energy-intensive process. Most of a cell's energy goes into making proteins.

At first sight, the idea that bacteria have nothing to gain by growing larger would seem to be undermined by the fact that there are some giant bacteria bigger than many complex cells, notably Epulopiscium, which thrives in the gut of the surgeonfish. Yet Epulopiscium has up to 200,000 copies of its complete genome. Taking all these multiple genomes into consideration, the energy available for each copy of any gene is almost exactly the same as for normal bacteria, despite the vast total amount of DNA. They are perhaps best seen as consortia of cells that have fused together into one, rather than as giant cells.

So why do giant bacteria need so many copies of their genome? Recall that cells harvest energy from the force field across their membranes, and that this membrane potential equates to a bolt of lightning. Cells get it wrong at their peril. If they lose control of the membrane potential, they die. Nearly 20 years ago, biochemist John Allen, then at Queen Mary, University of London, suggested that genomes are essential for controlling the membrane potential, by controlling protein production. These genomes need to be near the membrane they control so they can respond swiftly to local changes in conditions. Allen and others have amassed a good deal of evidence that this is true for eukaryotes, and there are good reasons to think it applies to simple cells, too.

So the problem that simple cells face is this. To grow larger and more complex, they have to generate more energy. The only way they can do this is to expand the area of the membrane they use to harvest energy. To maintain control of the membrane potential as the area of the membrane expands, though, they have to make extra copies of their entire genome – which means they don't actually gain any energy per gene copy.

Put another way, the more genes that simple cells acquire, the less they can do with them. And a genome full of genes that can't be used is no advantage. This is a tremendous barrier to growing more complex, because making a fish or a tree requires thousands more genes than bacteria possess.

So how did eukaryotes get around this problem? By acquiring mitochondria.

About 2 billion years ago, one simple cell somehow ended up inside another. The identity of the host cell isn't clear, but we know it acquired a bacterium, which began to divide within it. These cells within cells competed for succession; those that replicated fastest, without losing their capacity to generate energy, were likely to be better represented in the next generation.

And so on, generation after generation, these "endosymbiotic" bacteria evolved into tiny power generators, containing both the membrane needed to make ATP and the genome needed to control membrane potential. Crucially, though, along the way they were stripped down to a bare minimum. Anything unnecessary has gone, in true bacterial style. Mitochondria originally had a genome of perhaps 3000 genes; nowadays they have just 40 or so genes left.

For the host cell, it was a different matter. As the mitochondrial genome shrank, the amount of energy available per host-gene copy increased and its genome could expand. Awash in ATP, served by squadrons of mitochondria, it was free to accumulate DNA and grow larger. You can think of mitochondria as a fleet of helicopters that "carry" the DNA in the nucleus of the cell. As mitochondrial genomes were stripped of their own unnecessary DNA, they became lighter and could each lift a heavier load, allowing the nuclear genome to grow ever larger.

These huge genomes provided the genetic raw material that led to the evolution of complex life. Mitochondria did not prescribe complexity, but they permitted it. It's hard to imagine any other way of getting around the energy problem – and we know it happened just once on Earth because all eukaryotes descend from a common ancestor.

Freak of nature

The emergence of complex life, then, seems to hinge on a single fluke event – the acquisition of one simple cell by another. Such associations may be common among complex cells, but they are extremely rare in simple ones. And the outcome was by no means certain: the two intimate partners went through a lot of difficult co-adaptation before their descendants could flourish.

This does not bode well for the prospects of finding intelligent aliens. It means there is no inevitable evolutionary trajectory from simple to complex life. Never-ending natural selection, operating on infinite populations of bacteria over billions of years, may never give rise to complexity. Bacteria simply do not have the right architecture. They are not energetically limited as they are – the problem only becomes visible when we look at what it would take for their volume and genome size to expand. Only then can we see that bacteria occupy a deep canyon in an energy landscape, from which they are unable to escape.

So what chance life? It would be surprising if simple life were not common throughout the universe. Simple cells are built from the most ubiquitous of materials – water, rock and CO2 – and they are thermodynamically close to inevitable. Their early appearance on Earth, far from being a statistical quirk, is exactly what we would expect.

The optimistic assumption of the Drake equation was that on planets where life emerged, 1 per cent gave rise to intelligent life. But if I'm right, complex life is not at all inevitable. It arose here just once in 4 billion years thanks to a rare, random event. There's every reason to think that a similar freak accident would be needed anywhere else in the universe too. Nothing else could break through the energetic barrier to complexity.

This line of reasoning suggests that while Earth-like planets may teem with life, very few ever give rise to complex cells. That means there are very few opportunities for plants and animals to evolve, let alone intelligent life. So even if we discover that simple cells evolved on Mars, too, it won't tell us much about how common animal life is elsewhere in the universe

.

All this might help to explain why we've never found any sign of aliens. Of course, some of the other explanations that have been proposed, such as life on other planets usually being wiped out by catastrophic events such as gamma-ray bursts long before smart aliens get a chance to evolve, could well be true too. If so, there may be very few other intelligent beings in the galaxy.

Then, again, perhaps some just happen to live in our neighbourhood. If we do ever meet them, there's one thing I would bet on: they will have mitochondria too.

Nick Lane

Origin of Life: Dawn of the Living

THE ORIGIN OF LIFE

Dawn of the living

From New Scientist, 28 April 2016

Life must have begun with a simple replicator – but what was it, and how did it work? Michael Marshall reports

4 BILLION years before present: the surface of a newly formed planet around a medium-sized star is beginning to cool down. It's a violent place, bombarded by meteorites and riven by volcanic eruptions, with an atmosphere full of toxic gases. But then something extraordinary happens. A molecule capable of replicating itself arises.

This was the dawn of evolution. Once the first self-replicating entities appeared, natural selection kicked in, favouring any offspring with variations that made them better at replicating themselves. Soon the first simple cells appeared. The rest is prehistory.

Billions of years later, some of the descendants of those first cells evolved into organisms intelligent enough to wonder what their very earliest ancestor was like. What molecule started it all?

Back in the 1960s, a few of those intelligent organisms began to suspect that the first self-replicating molecules were made of RNA, a close cousin of DNA. This idea has always had a problem, though – there was no known way by which RNA molecules could have formed on the primordial Earth. And if RNA molecules couldn't form spontaneously, how could self-replicating RNA molecules arise? Did some other replicator come first? If so, what was it? The answer is finally beginning to emerge.

When biologists first started to ponder how life arose, the question seemed baffling. In all organisms alive today, the hard work is done by proteins. Proteins can fold into a wild diversity of shapes, so they can do just about anything, including acting as enzymes, substances that catalyse a huge range of chemical reactions. However, the information needed to make proteins is stored in DNA molecules. You can't make new proteins without DNA, and you can't make new DNA without proteins. So which came first, proteins or DNA?

The discovery in the 1960s that RNA could fold like a protein, albeit not into such complex structures, suggested an answer. If RNA could catalyse reactions as well as storing information, some RNA molecules might be capable of making more RNA molecules. And if that was the case, RNA replicators would have had no need for proteins. They could do everything themselves.

It was an appealing idea, but at the time it was complete speculation. No one had shown that RNA could catalyse reactions like protein enzymes. It was not until 1982, after decades of searching, that an RNA enzyme was finally discovered. Thomas Cech of the University of Colorado in Boulder found it in Tetrahymena thermophila, a bizarre single-celled animal with seven sexes.

After that the floodgates opened. People discovered ever more RNA enzymes in living organisms and created new ones in their labs. RNA might be not be as good for storing information as DNA, being less stable, nor as versatile as proteins, but it was turning out to be a molecular jack of all trades. This was a huge boost to the idea that the first life consisted of RNA molecules that catalysed the production of more RNA molecules – "the RNA world", as Harvard chemist Walter Gilbert dubbed it three decades ago.

These RNA replicators may even have had sex. The RNA enzyme Cech discovered did not just catalyse any old reaction. It was a short section of RNA that could cut itself out of a longer chain. Reversing the reaction would add RNA to chains, meaning RNA replicators might have been able to swap bits with other RNA molecules. This ability would greatly accelerate evolution, because innovations made by separate lineages of replicators could be brought together in one lineage.

Evolving replicators

For many biologists the clincher came in 2000, when the structure of the protein-making factories in cells was worked out. This work confirmed that nestling at the heart of these factories is an RNA enzyme – and if proteins are made by RNA, surely RNA must have come first.

Still, some issues remained. For one thing, it was unclear whether RNA really was capable of replicating itself.

Nowadays, DNA and RNA need the help of many proteins to copy themselves. If there ever was a self-replicator, it has long since disappeared. So biochemists set out to make one, taking random RNAs and evolving them for many generations to see what they came up with.

By 2001, this process had yielded an RNA enzyme called R18 that could stick 14 nucleotides – the building blocks of RNA and DNA – onto an existing RNA, using another RNA as a template. Any self-replicating RNA, however, needs to build RNAs that are at least as long as itself – and R18 doesn't come close.

A big advance came in 2013, when Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK, and colleagues unveiled an RNA enzyme called tC9Y. It is 202 nucleotides long, and reliably copies RNA sequences longer than itself, up to 206 letters long. To do this, tC9Y clamps onto the end of an RNA, attaches the correct nucleotide, then moves forward a step and adds another. "It blows my mind that you can do something so complex with such a simple molecule," Holliger says. Crucially, this enzyme does not yet copy itself and biologists have yet to pass this milestone. "There are various RNA systems that can assemble themselves from prefabricated pieces, but I would not call this self-replication, rather self-assembly," says Holliger.

There is another sticking point: where did the energy to drive this activity come from? There must have been some kind of metabolic process going on – but RNA does not look up to the job of running a full-blown metabolism.

"There's been a nagging issue of whether RNA can do all the chemistry," says Adrian Ferré-D'Amaré of the National Heart, Lung and Blood Institute in Bethesda, Maryland. RNA has only a few chemically active "functional groups", which limit it to catalysing just a few types of chemical reaction.

Functional groups are like tools – the more kinds you have, the more things you can do. Proteins have many more functional groups than RNAs. However, there is a way to make a single tool much more versatile: attach different bits to it, like those screwdrivers that come with interchangeable heads. The chemical equivalents are small helper molecules known as cofactors.

Proteins use cofactors to extend even further the range of reactions they can control. Without cofactors, life as we know it couldn't exist, Ferré-D'Amaré says. And it turns out that RNA enzymes can use cofactors too.

In 2003, Hiroaki Suga, now at the University of Tokyo, Japan, created an RNA enzyme that could oxidise alcohol, with help from a cofactor called NAD+ which is used by many protein enzymes. Months later, Ronald Breaker of Yale University found that a natural RNA enzyme, called glmS, also uses a cofactor.

Many bacteria use glmS, says Ferré-D'Amaré, so either it is ancient or RNA enzymes that use cofactors evolve easily. Either way, it looks as if RNA molecules would have been capable of carrying out the range of the reactions needed to produce energy.

So the evidence that there was once an RNA world is growing ever more convincing. Only a few dissenters remain. "The naysayers about the RNA world have lost a lot of ground," says Donna Blackmond of the Scripps Research Institute in La Jolla, California. But there is still one huge and obvious problem: where did the RNA come from in the first place?

RNA molecules are strings of nucleotides, which in turn are made of a sugar with a base and a phosphate attached. In living cells, numerous enzymes are involved in producing nucleotides and joining them together, but of course the primordial planet had no such enzymes. There was clay, though. In 1996, biochemist Leslie Orgel showed that when "activated" nucleotides – those with an extra bit tacked on to the phosphate – were added to a kind of volcanic clay, RNA molecules up to 55 nucleotides long formed. With ordinary nucleotides the formation of large RNA molecules would be energetically unfavourable, but the activated ones provide the energy needed to drive the reaction.

This suggests that if there were plenty of activated nucleotides on the early Earth, large RNA molecules would form spontaneously. What's more, experiments simulat2ing conditions on the early Earth and on asteroids show that sugars, bases and phosphates would arise naturally too. It's putting the nucleotides together that is the hard bit; there does not seem to be any way to join the components without specialised enzymes. Because of the shapes of the molecules, it is almost impossible for the sugar to join to a base, and even when it does happen, the combined molecule quickly breaks apart.

This apparently insurmountable difficulty led many biologists to suspect to RNA was not the first replicator after all. Many began exploring the possibility that the RNA world was preceded by a TNA world, or a PNA world, or perhaps an ANA world. These are all molecules similar to RNA but whose basic units are thought to have been much more likely to form spontaneously. The big problem with this idea is that if life did begin this way, no evidence of it remains. "You don't see a smoking gun," says Gerald Joyce, also of the Scripps Research Institute.

In the meantime John Sutherland, at the MRC Laboratory of Molecular Biology, has been doggedly trying to solve the nucleotide problem. He realised that researchers might have been going about it the wrong way. "In each nucleotide, you see a sugar, a base and a phosphate group," he says. "So you assume you need to make those building blocks first and then stick them together... and it doesn't work."

Instead he wondered whether simpler molecules might assemble into a nucleotide without ever becoming sugars or bases. In 2009, he proved it was possible. He took half a sugar and half a base, and stuck them together – forming the crucial sugar-base link that everyone had struggled with. Then he bolted on the rest of the sugar and base. Sutherland stuck on the phosphate last, though he found that it needed to be present in the mixture for the earlier reactions to work. "Sutherland had a real breakthrough," Holliger says. "Everyone else was barking up the wrong tree."

Goldilocks chemistry

Sutherland was being deliberately messy by including the phosphate from the start, but it gave the best results. That's encouraging: the primordial Earth was a messy place and it may have been ideal for making nucleotides. At that time, Sutherland suspected there was a "Goldilocks chemistry" – not too simple, not too complex – that would produce many key compounds from the same melting pot. In 2015 he proved it, showing that precursors to ribonucleotides, lipids and amino acids could be created out of two simple compounds abundant on early Earth – hydrogen cyanide and hydrogen sulphide – plus UV light.

The issue isn't entirely solved yet. RNA has four different nucleotides, and so far Sutherland has only produced two of them. However, he says he is "closing in" on the other two. If he succeeds, it will show that the spontaneous formation of an RNA replicator is not so improbable after all, and that the first replicator was most likely made of RNA.

Many questions remain, of course. What was the first life like? How did the transition to DNA and proteins, and the development of the genetic code, occur? We may never know for sure but many promising avenues are being explored. Most biologists think there must have been something like a cell right from the start, to contain the replicator and keep its component parts together. That way, individuals could compete for resources and evolve in different ways.

Jack Szostak of Harvard University has shown that the same clay that produces RNA chains also encourages the formation of membrane-bound sacs rather like cells that enclose cells. He has grown "proto-cells" that can carry and replicate RNA and even divide without modern cellular machinery.

Another idea is that life began in alkaline hydrothermal vents on the sea floor (see "Meet your maker"). Not only are these vents laced with pores and bubbles, but they also provide the same kind of electrochemical gradient that drives energy production in cells to this day. Conditions may have been ideal for producing long RNA chains.

Holliger has another idea: maybe it all happened in ice. At the time life began, the sun was 30 per cent dimmer than today. The planet would have frozen over if the atmosphere hadn't been full of greenhouse gases, and there may well have been ice towards the poles. Cold RNA lasts longer, and ice has many other benefits. When water laced with RNA and other chemicals is cooled, some of it freezes while the rest becomes a concentrated brine running around the ice crystals. "You get little pockets within the ice," Holliger says. Interestingly, the R18 and tC9Y RNA enzymes can work better in ice than at room temperature – tC9Y can even synthesise RNA at temperatures as low as -19 °C. And in 2015 Holliger and colleagues demonstrated that freeze-thaw cycles allow complex RNA molecules to spontaneously assemble from simpler ones.

Right now, there's no way to choose between these options. No fossilised vestiges remain of the first replicators as far as we know. But we can try recreating the RNA world to demonstrate how it might have arisen. One day soon, Sutherland says, someone will fill a container with a mix of primordial chemicals, keep it under the right conditions, and watch life emerge. "That experiment will be done."

Michael Marshall

Why are religions so judgemental?

From New Scientist Magazine – 28^th April 2016

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Why are religions so judgemental? Ask evolution

Nicolas Baumard

The rise of moralising religions like Christianity can be explained by evolution – and so can their eventual downfall, says evolutionary psychologist Nicolas Baumard

Forgive me, father

WHEN Jesus of Nazareth died on the cross, leaving behind a few dozen followers in a remote province of the Roman Empire, few would have guessed that 350 years later Christianity would be the official religion of the Roman Empire and would go on to become the most widely practised religion in the world.

Christianity's success is often attributed to its supposedly unique message. Unlike earlier religions, it exhorted people to be good and promised to reward them for their goodness in the afterlife. That is still how most people conceptualise the Christian message: helping others, working hard, controlling one's sexuality and believing that people who don't do so will be punished. In other words, a moralising religion.

It is true that before Christianity, most religions did not place a high value on morality. The Greco-Roman religions, for example, were materialistic, mostly concerned with rituals, sacrifices and other ways of begging favours from their various divinities.

But Christ's message was not actually new. In Homer's time, the 8th century BC, the Greeks believed that when people died they all, good and bad, went to Hades. From the 5th century BC on, Greeks started to believe that the dead were judged in Hades according to their deeds during life. Judaism, too, began to incorporate beliefs about moral punishment in the afterlife.

Roman religions were materialistic rather than moralising

 Parallel developments ccurred in societal values. While the heroes of Homer's Iliad were openly polygamous and unfaithful, fidelity and monogamy started to be promoted towards the end of the 1st century BC. Where Achilles and Agamemnon were quick-tempered, sexually rapacious and arrogant, the moralists of the Roman Empire started to defend an ethics of asceticism and modesty.

Social glue

Christianity, then, was part of a wave of new religions that emerged more than 2000 years ago. What happened to make materialistic religions transform into moralising ones?

Social scientists sometimes explain this by arguing that moralising religions promote cooperation, which would have given the societies that adopted them a competitive advantage. Religion was a sort of "social glue" that bound societies together as they grew beyond the point where everyone was related and family ties stopped people from freeloading. That seems a plausible explanation – except for the fact that moralising religions did not arise until quite late in human history, long after the rise of large-scale societies in Egypt and Sumeria.

Recent research in behavioural ecology and experimental psychology suggests a different answer. This work, known as life history theory, finds that organisms are endowed with evolved programmes that modulate their behaviour according to their environment. In a harsh and unpredictable environment, when resources are scarce and mortality is high, organisms adopt a "fast life strategy". They mature and reproduce earlier, invest less in offspring and pair-bonding, and are impulsive and aggressive.

For instance, starlings placed in a highly competitive environment for a few days during their development go on to invest less in physical maintenance, with a lower body weight and reduced levels of DNA repair. They also develop a fast psychology, preferring immediate rewards over riskier but potentially more profitable investments in foraging. From an evolutionary perspective this makes sense: if you could die at any time, your best shot of passing on your genes is to grab what you can.

In contrast, in a more favourable and predictable environment, organisms switch to a slow life strategy. They mature and reproduce later, invest more in offspring and pair-bonding, and become more patient and more forgiving.

The same ability to switch also exists in humans, and an abundant stream of research shows that as the environment gets better, individuals start investing more in their family and romantic relationships, and become less impulsive and less aggressive (New Scientist, 17 July 2010, p 40). For example, women from more affluent neighbourhoods are likely to have babies at a later age. They have larger babies and breastfeed more, both of which make it more difficult to get pregnant again.

This is strikingly similar to what happened in the eastern Mediterranean 2500 years ago. Around that time, energy use per capita – a good proxy for affluence – rose from the 15,000 calories per day typically seen in Egyptian and Sumerian civilisations to more than 20,000 calories per day. And as people became more affluent and society more stable and predictable, their slow strategy kicked in.

At the same time, we see the invention and spread of moralising religions. Are the two connected?

I think so. Consider the fact that for a long time, the switch from fast to slow strategy was restricted to only the most affluent members of the population. Everybody else was still living fast and dying young, and the elite were none too happy about it.

This may be explained by a general principle of human moral cognition – people intuitively disapprove of behaviour that threatens their interests. You are clearly at a disadvantage if you follow a slow strategy when others follow a faster strategy: if you are faithful when others grab sexual opportunities, if you forgive when others avenge, if you work when others have fun. This disadvantage incentivised the elite to morally condemn fast behaviours, in part by adopting and promoting the new religions that legitimised and reinforced a slow morality and promised punishment for transgressors.

The same idea could also explain the gradual decline of moralising religion in wealthier parts of the world such as Western Europe and the northern parts of North America. As more and more people become affluent and adopt a slow strategy, the need to morally condemn fast strategies decreases, and with it the benefit of holding religious beliefs that justify doing so.

If this is true, and our environment continues to improve, then like the Greco-Roman religions before them, Christianity and other moralising religions could eventually vanish.

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This article appeared in print under the headline "Morality tale"

Nicolas Baumard is an evolutionary psychologist at the École Normale Supérieure in Paris

April Fool's Day Religious Hoaxes

There are some notable April Fool's Day religious hoaxes, some of which are described here

But my favourite is Bob Carroll's conversion to religion