Life. The Universe. And Everything.

The origins of life have long fascinated philosophers and biologists, but amid all the theory, are we any nearer to finding a definitive answer?

Magazine: Portico Issue 2 2015/2016; Client: UCL

Once upon a time, 3.5 billion years ago, the Earth’s plates shifted slightly as it cooled. Somewhere in the depth of an ocean, a fissure opened up in the Earth’s crust, venting jets of hot water. The smorgasbord of chemical reactions that resulted created something new on a planet whose surface had previously been too hot for anything to arise.

This is one of the current theories about how life on Earth began. Over the years, there have been plenty of others: as simple as a lightning strike into what Darwin described as “warm ponds”; or the now widely discredited “panspermia” theory which suggests life came from outer space; or going back to Aristotle, the “spontaneous generation theory” in which life just sort of “happened”.

The question of the origins of life on Earth has been vexing researchers at UCL for many years. “I couldn’t find a bigger question than ‘Why does life exist on Earth?’” says Dr Matt Powner, Reader of Organic Chemistry at the Department of Chemistry. “It may take some time to solve all aspects of the transition from chemistry to biology, but the biggest driver for me has always been to play some part in understanding this huge question of why is life here. Why specifically here and why specifically the biochemistry we observe in all life?”

Life on earth isn't a battlefield

The search for the origins of life is a challenge, to say the least. But we have some clues. We know that the Earth formed about 4.5 billion years ago and that for the first several hundred thousand years it was too hot for any carbon-based life form. And we know that all living organisms today descended from a single living cell arising some 3.5 billion years ago. “The window for life beginning is quite small in geological terms – somewhere between a quarter and half a million years,” says Powner.

The “where” may also prove important. Some believe those fissures or “hydrothermal vents” at the bottom of the oceans (the Lost City Hydrothermal Field, for example, lies in the mid-Atlantic ocean, 2,600ft under the ocean’s surface) hold the key. According to Dr Nick Lane, leader of the UCL Research Frontiers Origins of Life programme, certain warm alkaline vents, rich in hydrogen and other minerals, are naturally electrically charged, and this could explain how cells began to generate energy. They do this through creating charged membranes that drive the chemical reaction between hydrogen and carbon dioxide. “All cells, from bacteria to human, have membranes which are charged,” explains Lane, author of e Vital Question: Why is Life the Way it Is?. “It’s amazingly strong. If you look at the electrical charge you would experience if you were the size of a molecule, it’s equivalent to a bolt of lightning.” Clues exist, but Lane, whose work on Chemiosmosis and the Foundations of Complex Life is funded by a UCL Provost’s Venture Research Fellowship award, admits the search for the origins of life is “the black hole at the heart of biology”.

Back in the 1970s, a new kind of simple celled organism was discovered, known as archaea. Many inhabit extreme environments such as ocean vents, but they can also be found in dental plaque. It is now clear that all complex cells, like those of animals, plants and fungi, originated from an archaeon engulfing a bacterium around one billion years ago. The echoes of this event are still present in our DNA. The bacteria eventually became mitochondria, the cellular powerplant. The search is on for the archaea from which all complex life evolved and a recent candidate is looking good – an organism called Lokiarchaeota has genes that make many of the important proteins found in our cells. “It looks really like our sister group,” says Professor Buzz Baum, Professor of Cell Biology at the MRC Laboratory for Molecular Cell Biology at UCL.

From an evolutionary standpoint, we think of life as “survival of the fittest”. But recent research suggests that actually a spirit of co-operation may be at the heart of the first complex cell. Baum recently published a paper on just how archaea and bacteria could have come together – the archaea, he says, rather than engulfing the bacteria, began co-operating, eventually merging into one cell with a new membrane. “Darwinian evolution is about survival of the fittest – two deer fight, the strongest gets the mate,” he says. “But the biggest transitions in life on Earth came from different cells working together. You shouldn’t see life as a battle field – it’s many things living together.” It’s a comforting thought that our cells might have evolved through co-operation, not conflict.

Life has adapted to the most insane conditions

To better understand the origins of this co-operation, researchers at UCL are
reconstructing the conditions under which modern archaea – close relatives of our distant ancestors – can grow. “We’re trying to image cells dividing at temperatures as high as 76°C with a super-resolution microscope,” says Baum of this particular piece of radical thinking. It can be difficult though, he says, as microscopes are not made to withstand these conditions. “But it’s really fun, because nobody else in the world has seen these cells changing shape and dividing. We hope to be the first.”

Given the sheer diversity of life on Earth it is amazing that everything stems from the same source. “Life has adapted to the most insane conditions and the way that these different organisms look is also extremely diverse. Yet the stuff they are made of – the amino acids and the nucleotides and the carbohydrates and the lipids – are near identical,” says Professor Finn Werner, Wellcome Trust investigator and team leader of the UCL RNA polymerase laboratory. You can try an experiment: get a microscope
and place a mushroom cell and a human cell next to each other. It’s actually very hard to tell the difference – the cells are basically the same size and shape and have many similar elements. Werner says: “It’s not the components that create the huge diversity of life, but rather the biological information encoding them, the big blueprint of life and its realisation by the precise execution of a genetic programme.” Understanding the origins of life means also understanding how these processes developed.

Werner is also studying archaea to understand how basic cellular processes might have developed, such as how genetic information is interpreted by the cell in a process called gene expression. Important to that process is the molecule RNA – a simpler version of DNA, now responsible for making proteins, and probably the first self-replicating molecule on the planet before cells. “Without time machines we can’t go back and investigate what it really looked like, but we can study the enzymes that synthesise RNA in organisms that are alive today,’’ says Werner. He is comparing the different structures and functions of complicated molecular machines, called RNA polymerases, which make RNA itself, to gain an understanding of how genetic information was processed. “Archaea are the absolute key to this research,” he says.

Complexity derives from a very few core small molecules

Where is this quest for the origins of life likely to lead us? The answer is limitless but, importantly, there could be many positive effects from the work being done. Baum’s work on cell shape and division is funded by Cancer Research UK, and it could well have implications for our knowledge of what damages cells during the division process – which in turn could help us understand cancer better. As Werner says: “Without this type of fundamental research there will be no way to translate our knowledge into the development of new treatments and practices in the future.”

But Werner also argues that research into the origins of life is not primarily about improving human health. “It’s more than that, it’s fundamentally about understanding where we came from.” We are slowly reassembling the jigsaw puzzle of life but, as Nick Lane says, “we are a long, long way from building the puzzle at the moment – we are still dealing with jigsaw pieces and we don’t even know if all the pieces are from the same puzzle”.

Lane says we may not ever really know exactly how life arose billions of years ago, but this doesn’t matter. “ That’s not actually what we are trying to do.” He says what is important is understanding how it could have started. “We can understand the principles that convert a sterile planet with rock, water, carbon dioxide and an atmosphere into the living world around us.”

Werner says this requires a concerted and particularly interdisciplinary effort, such as 
that demonstrated at the Institute for the Physics of Living Systems. “In the RNAP lab we use biophysics, structural, molecular and systems biology as well as computational tools. In order to create plausible theories on the origins of life many aspects have to be rationalised: energy, metabolism, information and cell partition are all equally critical. Scientists from a broad range of disciplines have been researching the individual components for decades, but they have looked at these problems in isolation. I think the biggest task is to reconcile all these independent theories in a unified theory of the origins of life. This is possibly the greatest challenge of science ever – but it is within reach, and coming closer with every experiment we conclude successfully."