When it comes to an explanation for the origin of life, there’s only one thing that scientists agree on: we still don’t have one.
Perhaps 4 billion years ago, life arose in the tempestuous environment of the immature Earth. Quite what is meant by ‘life’ in its earliest forms is still hotly debated, although a defining moment has to be when some molecule found a way to reproduce itself with near (but not quite) 100% accuracy. From that point onwards, Darwinian evolution can do the rest. So the real challenge for origin-of-life scientists is to explain how the first self-replicating molecule arose. There are plenty of ideas.
A good place to start the search for this explanation is more than half a century ago in 1953. Chicago University graduate Stanley Miller and his supervisor Harold Urey produced amino acids by electrifying a “primordial soup” of methane, ammonia, hydrogen and water. Their sensational experiment showed how simple ingredients that could have been around on the early earth might have spawned the building blocks of proteins – Nature’s chemistry set.
But it was also in 1953 that Francis Crick and James Watson suggested that double-helical DNA might contain a genetic code. The subsequent discovery of DNA transcription into RNA and RNA translation into protein raised a serious paradox for those contemplating the origin of life.
It’s a chicken-and-egg situation. Even if Miller and Urey’s amino acids had been produced in an inorganic soup, how could they be strung together in the right order without DNA instructions? Yet the transfer of information from DNA to RNA to protein would require proteins themselves to run the complex reactions. So which came first: the genetic material or the protein?
RNA offered the most plausible route out of this chicken-and-egg loop of logic. In the 1960s, Carl Woese of the University of Illinois, Francis Crick at the UK’s Medical Research Council and Leslie Orgel of the Salk Institute in San Diego independently proposed that RNAs capable of both coding and catalysis could be the secret of life without DNA or proteins. Empirical evidence for these so-called “ribozymes” emerged in the early 1980s and Harvard University professor Walter Gilbert coined the phrase “RNA World” in an article in Nature in 1986. “I wish I’d thought of it, admits Dr Orgel. “Having a neat name for things attracts a lot of attention.”
Increasingly, it looks like the attention is warranted. Although the RNA world ribozymes have been extinct for nigh-on 4 billion years, contemporary organisms still harbour evidence of this ancestral era. One of the most exciting developments for fans of the RNA world was the revelation that that the enzyme at the heart of the ribosome condensing amino acids into peptides is not a protein but a ribozyme. “This is probably a fossil of that RNA world that has persisted ever since,” says David Lilley, head of the Cancer Research UK Nucleic Acid Research Group at the University of Dundee, Scotland.
Much of Professor Lilley’s research is focused on understanding how contemporary ribozymes pull off their catalytic tricks. “The present day ribozymes do a very limited range of chemistry,” he says. Nevertheless, this kind of forensic inspection of their folding ability could give us an insight into the RNA world. “In my more fanciful moments, I like to think I’m glimpsing what a world 3.6 billion years ago must have been like.”
Yet more support for an RNA world comes from artificial selection of RNAs in the laboratory. “This so-called in-vitro evolution is a model for RNA evolution in the RNA world,” says Gerald Joyce, professor of chemistry and molecular biology at The Skaggs Institute for Chemical Biology. “It has been used to develop ribozymes that catalyse each of the component reactions of protein synthesis,” he says.
Ribozymes would push the origins of life back, but not to the beginning. RNA is a complex molecule – a long string of nucleotides, each comprised of a ribose, a phosphate and one of four bases (adenine, guanine, thymine and cytosine). So how did it come into existence? Again, there are plenty of ideas.
For example, some clay minerals will catalyse the formation of shortish RNA sequences from a cocktail of nucleotides, says James Ferris, director of the New York Center for Studies on the Origins of Life. “I’m proposing that out of these similar structures you’re going to have one capable of catalysis.” His research, however, doesn’t account for the formation of the bases in the first place and their incorporation into nucleotides. “This is still a big problem,” Professor Ferris admits.
Another possibility is that there were terrestrial ponds that, as they evaporated, concentrated the organic building blocks until a Miller-Urey-type reaction resulted in strands of RNA. The problem with this idea is that the pools risk drying out long before any interesting chemistry can get going.
What if all these reactions took place underwater? Hydrothermal vents at the bottom of earth’s early ocean is the site favoured by William Martin, professor of biochemistry at the University of Düsseldorf in Germany and Michael Russell, professor of geology at the Scottish Universities Environmental Research Centre in Glasgow.
The vents would not have been of the volcanic “black smoker” variety but more like the “lost city” vent system in the Atlantic, says Martin – a warm, alkaline and reduced solution passing through the crust to meet the cooler, more acid and relatively oxidised ocean. The strong temperature and redox gradients at these vents would have made them a hive of chemical activity.
The lost city vents, which lend support to their idea, contain thousands of naturally formed calcium carbonate microcavities. At the origin of life, suggests Professor Martin, hydrogen and carbon dioxide bubbling through similar iron-sulphide reaction chambers would have formed acetyl-thioesters, crucial and central intermediates in the biochemistry of all modern life.
There’s more. “Hydrothermal vents today circulate the entire volume of the ocean about every 100,000 years,” says Professor Martin. This means there were probably plenty of other interesting ingredients passing through these vents and concentrating in their reaction chambers. It’s within the realms of possibility that these could have produced all the building blocks needed for the RNA world, he says.
Others, however, including RNA-world originator Dr Orgel, have come round to the idea that RNA itself is too complex to have been the first self-replicating molecule. If they’re right, there may have been a pre-RNA-world world, which helped put some of the complexity in place.
But was there enough time for all this complex train of molecular evolution to run its course on earth? The early Earth experienced high temperatures, intense volcanic activity and relentless bombardment by meteorites – not the best conditions for the formation of complex organic compounds. This doesn’t leave much time for life to emerge, says Nigel Mason, professor of physics and astronomy at the Open University in Milton Keynes, UK. This raises the possibility that some of the ingredients of the first self-replicator could have hitched a lift to earth on a meteorite or comet, he says.
If all of this sounds too improbable, then maybe a dose of quantum mechanics can help. The stuff of atoms – protons and electrons – don’t have regular positions in space and time but exist as a kind of fog of all possible positions and states, says Johnjoe McFadden, professor of molecular genetics at the University of Surrey and author of Quantum Evolution. The chances of making useful ingredients by classical chemical reactions may be minute, but the quantum fog model would potentially generate a much larger number of chemical entities. It may seem far-fetched but, Professor McFadden points out, quantum effects have recently been seen to be important in enzyme function. This kind of thinking may be needed to explain the origin of the first self-replicating molecule, he says.
As befits the biggest question facing biology, there’s plenty of brain fodder to grapple with. The origin of life is a soluble problem, says Dr Orgel. “I’d hate to have to guess how long it will take,” he says. “Until it’s done you can’t be sure.”
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