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How life first emerged in a non-living world

How big is the universe? What really is consciousness? How did life begin on earth?

The quest for finding the above answers has kept us occupied ever since we first started thinking about our place in the cosmos. For the longest time, the standard explanation for everything was, “…the Gods did it”, and dissenters were routinely branded heretics, tortured, and even killed.

Fortunately for us, times have changed. Over the last few centuries, we have devised wildly ambitious experiments to unlock the secrets surrounding these mysteries. As for life, they’ve even tried to recreate it in the lab, and while no one has been successful – we’ve found some fascinating answers.

This is the story of abiogenesis, the process of how life first originated from, well, not life. In order to answer how life began, we must first look at where and when it began. Buckle up because our first stop takes us 4.6 billion years ago.

Earth before life

The Earth always wasn’t a blue-green globe with oceans, clouds, terrain, teeming with plant and animal life. The Hadean Earth (period lasting from 4.6 billion to 4 billion years ago) was marked by its inhospitable environment made of a thick blanket of carbon dioxide, carbon monoxide, hydrogen sulphide, methane, ammonia, and other chemically reducing gases, constant lightning strikes, surface temperatures of around 230 degrees Celsius. With hardly any surface to speak of, it was constantly bombarded by meteorite showers into a hot molten pulp, and the atmospheric pressure was so high that water remained in the liquid state even at temperatures well above its boiling point.

Hadean
Is it just us or does early Earth pretty much look like the biblical description of hell? | Image credit: Tim Bertelink

The first person who attempted to study the preconditions that led to the creation of life was a Soviet scientist named Alexander Oparin. In 1924, he published The Origins of Life and laid out the model for how Earth cooled down following the Hadean period, creating the conditions for the emergence of sugars and amino acids in the Earth’s waters – molecules central to life.

A few years later, an English biologist named J.B.S. Haldane independently proposed similar ideas in a short article published in the Rationalist Annual. Oparin and Haldane thus helped shape the “primordial soup” model of abiogenesis where life could, in fact, emerge organically from the right chain of chemical reactions under suitable external conditions. As compelling as Oparin and Haldane’s hypotheses were, there was no proof.

Recreating life in the lab

What are the fundamental blocks that come together to create life? If we know what they are, can we recreate life in the laboratory? You would think that post the primordial soup model, things would become simpler to explain. But you would be very wrong.

Harold Urey won the 1934 Nobel Prize in Chemistry for his pioneering work on isotopes and later helped build the atomic bomb. Post the World War II period, he became interested in the chemistry of outer space during the formation of the solar system. One day while delivering a lecture, he spoke about how the lack of oxygen on Earth offered the perfect conditions for life in the models presented by Oparin and Haldane – the fragile chemicals would have been destroyed if they came in contact with oxygen.

SLMiller
You can say the results were… electrifying. | Image credit: NASA

 

In the audience was doctoral student Stanley Miller (pictured above), who approached Urey and presented an experiment intended to recreate the environment of early Earth. Conducted in 1952, this later famously became known as the Miller-Urey experiment. Miller mixed methane, ammonia, and hydrogen in a flask, then passed water vapour through this while simulating lightning strikes using an electrode. After a day, the solution had turned pink and continued to turn into a deeper shade of red as the experiment went on for a week. When Miller analysed the solution, he was able to identify two amino acids: Glycine and alanine. This was huge.

Amino acids are considered to be the building blocks of life. By demonstrating that you could create organic molecules from inorganic matter, given the right conditions, the Miller-Urey experiment secured its place as a breakthrough in abiogenesis research. However, there was a problem, it still offered no useful insights into how actual living beings may have evolved from those simple amino acids, and that’s where the real complexity was.

Biologically, a cell is the basic unit of life – you can examine anything from amoeba to human tissue under a microscope and you will see the same thing – self-contained entities that are capable of harnessing energy and self-replication, each made up of complex molecular structures called organelles. It was hard to conceive how amino acids could huddle together to make up all that stuff. A link was found but the big picture was still missing pieces.

Cell
Hey, you wanna try making one of these at home? Be my guest.

Origin theories

Abiogenesis is replete with theories, some of them contradictory, others plain ridiculous, scientists are known to form tribes and even polarise journalists against the “opponents” by calling their research stupid. Here, we look at the most plausible ones.

Have you ever thought about how difficult it is to pin down what being alive means? Is it the presence of hydrocarbons? Well, sugar has hydrocarbons, but it’s not really alive. Is it the process of consuming energy and creating excrement? Fire fits the description, it certainly isn’t alive in any way we think. Is it having a soul? Whatever that means? Not really, now we’re stepping out of science and going into metaphysics and folklore. So then what is it?

Most scientists now agree on a few essential features that define what is living: The ability to harness energy for sustenance, a mechanism for self-replication, and means of self-preservation. Most proposed models of abiogenesis take one of those features and try to build a valid theory by trying to fit in the missing parts.

While Stanley Miller was trying to create organic molecules from non-living matter, Alfred Hershey and James Crick were trying to crack the code of life at the University of Cambridge in UK. In 1952, they proposed the double-helix structure of DNA, or deoxyribonucleic acid – the molecule that carried genetic information in living organisms. DNA informs cells how to synthesise proteins, but DNA is too precious and is therefore guarded closely within the nucleus. Another molecule called RNA acts as the messenger between DNA and protein. A British chemist named Leslie Orgel first proposed that RNA is the prime candidate for the molecule that existed in the primordial soup that first began creating copies of itself while also having the ability to synthesise proteins.

DNA
I have a joke about DNA but you’ll just copy it.

Unfortunately, after decades of research, no one was able to synthesise nucleotides (the molecules that make RNA), no trace of self-replicating RNA has been found in nature, and no one has been able to explain how it might have first emerged in the primordial soup. Despite its shortcomings, the RNA World theory remains one of the most important theories that attempts to explain abiogenesis. It may not have been able to solve the mystery, but it certainly laid the groundwork for further research. Even other theories depend heavily on the findings from RNA World while constructing newer models for the origin of life.

While the RNA World theory had hit a dead end, another was picking up steam, centred around the idea that before life self-replicates, it must first know how to harness energy. We now know that when a cell needs energy, it breaks a third phosphate off the molecule adenosine triphosphate (ATP) – releasing energy in the process. This is how cells store and release energy. But how exactly do cells make ATP?

Biochemist Peter Mitchell, who later won the 1978 Nobel Prize in Chemistry, supplied the answer: The cells were pumping charged particles called proton across the membrane to supply the energy, in other words, cells have a proton gradient.

Q: What was the turning point in your research?

“The insight that most changed my approach to the origin of life was simply that we had to think about the origins of cells and not simply the origins of separate components such as membranes, genetic materials, and peptides. Ever since, the assembly of primitive cells that grow, divide and evolve has been the focus of research in my laboratory.”

Dr. Jack W. Szostak 
Winner of 2009 Nobel Prize for Physiology or Medicine, Professor of Chemistry and Chemical Biology, Harvard University.

Geologist Mike Russell, Deborah Kelley of the University of Washington, and biologist William Martin found a spot with natural proton gradient: Deep sea alkaline vents with the chemical energy needed to first make simple hydrocarbons and then complex molecules like RNA. This model provided a viable alternative to primordial soup for explaining abiogenesis. Unfortunately, this is where we hit another roadblock in our journey. Critics maintain that the reactions needed for the Deep-sea Vent theory to work are actually incompatible with water. The RNA World and Deep-sea Vent theories presented compelling ideas about abiogenesis, unfortunately, neither theories could reach a fitting conclusion. This is when Pier Luigi Luisi of Roma Tre University presented an alternative based on the idea of self-preservation.

Seavents
This might explain all those weird deep-sea creatures with four eyes and ten limbs.
Image Credit: U.S. National Oceanic and Atmospheric Administration

His reasoning was simple but hard to refute: How can you have either metabolism or self-replication unless you first have a container to keep the cell structures secure? In the biological world, this task is accomplished by the cell membrane – a barrier between the organelles and the outside environment – made from two layers of insoluble fatty acids called lipids. Jack Szostak, who previously worked on the RNA World hypothesis, teamed up with Luisi to create the crude predecessor to the biological cell, essentially blobs of lipid that they called the protocell. Then, they injected RNAs into protocells and studied their behavior.

The Lipid World theory had some spectacular successes. First, it demonstrated that protocells can split without spilling out their molecular guts, mirroring the process of fission in biological cells. Second, by adding a type of clay called montmorillonite, the vesicles formed hundred times faster, meaning, the protocells now had genes in the form of RNA and a catalyst in the form of clay, all in one neat lipid enclosure. This is the closest we have come to recreating a biological cell in the laboratory from scratch.

Lipid world
Next time someone calls you fat, start describing the Lipid World theory of abiogenesis—that’ll shut ‘em up

All the theories so far tried to build the model of life on top of essential biological processes, but each missed the mark in explaining the larger picture. John Sutherland of the Laboratory of Molecular Biology in Cambridge UK had been following abiogenesis closely. He thought if he could just synthesise RNA nucleotides in the lab, we would get closer to finding the answer.

Each RNA nucleotide is made of a sugar, a base, and a phosphate, but sugar and base don’t pair up easily owing to their different molecular shape. Sutherland’s breakthrough was using cyanamide as a catalyst to induce an alternate chain of reactions, by doing this he was able to produce two of the four RNA nucleotides. It was a home run.

Sutherland was still sceptical of RNA World, it seemed like an oversimplification to him. RNA was an important part, but not the holy grail. So he tried to build a more cohesive theory that took the best aspects of the previous ones and presented something more complex than the primordial soup: A place where cells could self-assemble all at once. According to Sutherland, there might have been a lake somewhere exposed to UV radiation that contained a hodgepodge of chemicals including water, hydrogen, ammonia, methane, phosphates, clay, minerals, and catalysts, precursors to lipids… the messier this concoction, the better, as it allows for more possibilities in chemical synthesis. Then perhaps one day, a rudimentary first cell assembled itself from this chemical soup and thrived in the presence of a suitable environment and absence of natural predators. This may seem too far out but it’s more plausible in its complexity in relation to previous theories.

Q: What was your eureka moment?

“In 2005, I had been struggling for weeks with an energetic chicken-and-egg problem. When I realised that geochemical synthesis of methyl groups would solve that problem, things made sense quickly. It seemed almost illogical at the time, but today we know that hydrothermal systems generate methane, meaning that the methyl groups have to be there, too.”
Dr. William F. Martin 
Institute of Molecular Evolution, University of Düsseldorf.

As you may have guessed by now, it’s exceedingly hard to either fully accept one theory of abiogenesis or fully write off another one. RNA World, Deep-sea Vents, Lipid World, and Hodgepodge World, all attempt to reveal the formative stages of the intricate machinery that goes into the making of every single living cell today, and thus, life itself.

Space may be the final frontier, but even here at home, there are puzzles still begging to be pieced together. In the meantime, we can marvel at the staggering complexity and sheer improbability of the chain of events that led us here.

This article was first published in the June 2017 issue of Digit magazine. To read Digit’s articles first, subscribe here or download the Digit app for Android and iOS. You could also buy Digit’s previous issues here.

Vishveshwar Jatain