“…all the organic beings which have ever lived on this earth may be descended from some one primordial form.” — C. Darwin
“…ummmm, but where does that one primordial form come from?” — S. Duuude
The visionary…
In 1924 a Soviet biochemist named Alexander Oparin published a very influential book called The Origin of Life. In this book Oparin speculated that the early Earth had a strongly reducing atmosphere, meaning that if oxygen was present it would have reacted immediately with the components of this primitive atmosphere. The specific gases Oparin thought might be present in that time included methane, ammonia, hydrogen and water, the first three of which we know react strongly with oxygen and are flammable. These gases were the raw materials for possible organic compounds and ultimately for living organisms.
According to Oparin, the gases initially reacted to form simple organic molecules, which gradually gained complexity and new properties. These complex organics accumulated in the primitive ocean and formed a primordial soup. The chemicals self-organized within this soup, much as we know that organic compounds today can form droplets and layers, and thus formed the first proto-cell.
About the same time in 1929 John Burdon Sanderson Haldane published an essay called The Origin of Life, which also proposed a similar hypothesis. The interesting thing is that Haldane proposed a sequence roughly similar to our early Earth summary, saying:
“…we may, I think, legitimately speculate on the origin of life on this planet. Within a few thousand years from its origin it probably cooled down so far as to develop a fairly permanent solid crust. For a long time, however, this crust must have been above the boiling-point of water, which condensed only gradually. The primitive atmosphere probably contained little or no oxygen, for our present supply of that gas is only about enough to burn all the coal and other organic remains found below and on the Earth’s surface. On the other hand, almost all the carbon of these organic substances, and much of the carbon now combined in chalk, limestone, and dolomite, were in the atmosphere as carbon dioxide. Probably a good deal of the nitrogen now in the air was combined with metals as nitride in the Earth’s crust, so that ammonia was constantly being formed by the action of water. The Sun was perhaps slightly brighter than it is now, and as there was no oxygen in the atmosphere the chemically active ultra-violet rays from the Sun were not, as they now are, mainly stopped by ozone (a modified form of oxygen) in the upper atmosphere, and oxygen itself lower down. They penetrated to the surface of the land and sea, or at least to the clouds…”
Haldane went on the propose that ultraviolet light from the sun acted on water, carbon dioxide and ammonia to yield a wide array of organic materials including sugars and the components of proteins. He suggested these would accumulate in oceans to form a “hot dilute soup”. The first precursors to life would have existed in this soup as a habitat of endless resources, processed by fermentation.
Although there were tremendous similarities in these two origins of life hypotheses, there were significant differences in their focus. Oparin focused much more on metabolic processes and on self-organizing molecules he called coacervates. Haldane, meanwhile, focused in subsequent work on molecules responsible for heredity.
Either way, both Oparin and Haldane significantly influenced origin of life research for decades to come, indeed to this day.
The mad scientist…
In the early 1950s a young Ph.D. candidate at the University of Chicago named Stanley Lloyd Miller was monitoring his experiment that looked exactly like a Hollywood mad scientist setup: odd shaped glassware connected by a maze of glass tubes, Bunsen burners boiling colored liquids, and the requisite electrodes spitting lightning into a bottle filled with eerily glowing gases.
This was the famous first origin of life experiment which showed that a few simple gases under the right conditions (conditions thought to simulate those in an early, primitive and lifeless Earth) can combine to form more complex organic molecules found in all life… amino acids, which are the building blocks of proteins.
The gases Miller used were the very simple molecules methane, ammonia, water vapor, and hydrogen, all of which were hypothesized to exist in the early Earth’s atmosphere. A flask contained boiling water to simulate primitive oceans. Electrodes poking into one of the larger flasks emitted electrical discharges to simulate lightning.
From this mixture of simple gases, Miller showed that the flask simulating the early ocean accumulated a range of organic molecules including the amino acids aspartic acid, glycine, and alanine. There are about 20 amino acids commonly found in proteins in biology, a few rare amino acids, and many more that are not found biologically (or not found yet). Miller described how his miniature ocean first turned pink within a day, and gradually became a deep red. In subsequent years and as a professor with his own multiple generations of graduate students, Miller was able to synthesize almost all biologically relevant amino acids and many other complex organic compounds under various conditions reflecting new hypotheses about the Earth’s atmospheric chemistry.
Miller’s Ph.D. supervisor was Harold Clayton Urey who, similar to Oparin and Haldane, also hypothesized that the early Earth atmosphere was composed of methane, ammonia and hydrogen (Urey won the Nobel Prize in Chemistry in 1934 for discovering deuterium, and developed isotope separation by gaseous diffusion to enrich uranium for the Manhattan Project).
Other scientists not only confirmed Miller’s results, but showed that other sources of energy including ionizing radiation, also yielded complex organics from simple precursors.
A key objection to Miller’s work is the necessity for a reducing atmosphere, with some critics looking to asteroids and comets for these organic compounds on the early Earth.
Carbonaceous chondritic meteorites have long been known to contain organic materials, and these meteorites originated from asteroids that are known to reflect the chemistry of the solar system’s origins. The Murchison meteorite that fell in Murchison, Victoria, Australia in 1969, was analyzed the following year and shown to contain amino acids and other organic materials. Importantly, the analysis ruled out terrestrial contamination which plagued earlier attempts to analyze meteorites.
Rupert Wildt, a German-American astronomer showed in 1932 that Jupiter had methane among other gases in its atmosphere. Therefore, extraterrestrial presence of organic materials was long known. Complex organic compounds including amino acids, however, had been hypothesized but not demonstrated until the analysis of the Murchison meteorite.
Miller’s experiment was the first bit of evidence that simple molecules and natural processes can generate organic compounds necessary for life — and also that we might lift the curtain on the far distant time before the beginning of life on Earth. Miller’s experiments also demonstrated conceptually that complex organics may be synthesized either here on Earth or on an asteroid or other body.
An even madder scientist…
1953, the same year that Miller wrote his groundbreaking paper on the synthesis of amino acids, Francis Crick and James Watson published an even bigger world-shaking paper announcing the structure of deoxyribonucleic acid — DNA.
Although in 1953 there were some hints that DNA was the cellular material in which genetic information was encoded, it was by no means the consensus at the time. Most scientists then believed that proteins were the only biochemical component of cells with sufficient complexity to encode all the genetic information not only for a cell, but for an entire organism.
Watson and Crick had stolen Rosalind Franklin’s unpublished x-ray crystallography data and correctly reconstructed the structure of DNA and eventually persuaded the scientific community that DNA was indeed the genetic material and proteins were not.
Watson, Crick, and Franklin’s supervisor Maurice Wilkins, all got the Nobel Prize in Medicine in 1962. In 1968, Watson published The Double Helix: A Personal Account of the Discovery of the Structure of DNA. In this book, Watson disparaged and demeaned Franklin, causing Crick to protest and ultimately fight its publication (which he ultimately lost). Franklin had become friends with Crick and his wife in the years following the DNA debacle, despite their inauspicious beginning. Franklin died of cancer in 1958. She was 37 years old.
Crick followed up in 1988 with his own book, What Mad Pursuit: A Personal View of Scientific Discovery.
In 1958, Crick elucidated what became known as the Central Dogma of molecular biology which stated that: information about the sequence of amino acids that make up a protein flows from DNA to RNA to protein.
The question for origin of life research then became which came first (DNA or RNA or protein) and how did the information for building proteins and living organisms first become encoded and transmitted?
Between 1966–68 Crick, simultaneously with other researchers, Leslie Orgel and Carl Woese, proposed that RNA was the original genetic code. This was the origin of what later became known as The RNA World hypothesis.
The main problem with the RNA World hypothesis was that proteins at the time were the only known biochemical with the ability to act as enzymes, or biological catalysts that dramatically speed up otherwise reluctant chemical reactions.
Catalysts and enzymes achieve their chemical activity by reducing what is called the activation energy, which can be thought of as a chemical speed bump that acts to slow down chemical reactions. By lowering the activation energy, enzymes are able to dramatically accelerate reactions that would otherwise be far too slow to support life. At the time, proteins were the only known biological enzymes.
This changed in the mid-1980s, when for the first time, RNA molecules were discovered which had enzymatic activity on other RNA molecules. Thomas R. Cech’s lab discovered an RNA in an organism called Tetrahymena thermophilia that had the ability to both cut and join other RNA molecules. This earned Cech a Nobel Prize in Chemistry in 1989. And this breathed new life into the RNA World hypothesis.
Now the question was how were the building blocks of RNA, the nucleotides, synthesized in the prebiotic world? Actually, this had been answered two decades before Cech’s discovery of RNA enzymes.
Spanish cooking — the ingredients of life…
In 1960, Joan Oro, a Spaniard who had just a few years earlier earned his Ph.D. at the University of Houston, succeeded in synthesizing adenine under young-earth-like conditions. Adenine is a small nitrogen-containing base, a ubiquitous biochemical used in many reactions throughout biology, and it is one of the four essential bases (the letters A, G, C, T or U of the genetic code) in DNA and RNA. Oro and others in the following years succeeded in synthesizing the other bases guanine, cytosine, thymine and uracil (uracil replaces thymine as one of the four bases in RNA).
Another major question at that time, spurred by Miller’s experiment, was how to link several amino acids together into a chain, and ultimately into a protein, in the prebiotic world. Oro was again at the forefront and managed to link a series of glycine amino acids into a polyglycine chain. We cannot call these proteins, as proteins have a specific and complex combination of many amino acids, and this much longer chain usually folds up into a particular 3-dimensional shape which gives it a very specific structural or enzymatic function. Nonetheless this work appeared to address the polymerization of amino acids in a prebiotic environment.
One of the defining components of a cell is the cell membrane, analogous to the skin of a cell. Today our cells are composed of phospholipids, similar to fats and a type of molecule called a lipid. Fatty acids are the simplest of the lipids, and are the type of molecule from which more complex lipids such as phospholipids are derived. It was not until the late 1970s that Oro and others were first able to synthesize fatty acids as well.
Oro made many important contributions to origin of life research by showing how prebiotic chemistry could synthesize many essential biochemicals. But one question he was not able to address was how nucleotides like adenine might have further polymerized into the first genetic material like DNA or RNA.
A team from the University College of London and Harvard University published a Nature paper in 2016 which showed how they synthesized a set of RNA precursors from common raw materials. Previous efforts by Oro and others required different starting materials and conditions, which argued against the RNA World hypothesis.
Even more exciting was the 2014 publication by a team from University of California Santa Cruz and NASA showing that these individual nucleotide components can be polymerized into small RNA molecules without the need for enzymes, and in environments suggestive of shallow pools near active volcanoes, pools which can alternate between wet and dry.
A rift in the science…
So far, all the origin of life hypotheses focused on variations of early atmospheric gases that react, thanks to electrical or UV or other energy sources, into more complex organic precursors that rain down into the early oceans, forming the primordial soup that gives rise to the first life on Earth.
In the 1970s a team led by John Corliss, Richard von Herzen, and Robert Ballard discovered submarine hydrothermal vents in the Galapagos Rift in the southern Pacific using the deep-sea submersible Alvin. Corliss was one of the crew in the Alvin when they discovered bizarre and amazing creatures like giant tube worms, clams, mussels and limpet thriving around these deep-sea volcanic vents spewing poisonous superheated gas- and metal-laden water. (Ballard was a diver on the team who later went on to fame by discovering the Titanic and other historical wrecks.). Importantly, the team discovered high concentrations of hydrogen sulfide dissolved in the waters surrounding these vents, as well as tremendous concentrations of sulfur-metabolizing bacteria. The huge concentrations of bacteria, thriving in and on the hot minerals within these vents, spilled out and fed the masses of unique deep-sea vent creatures. Corliss noted that this deep-water ecosystem was isolated from solar energy. Corliss quickly linked these discoveries to the possible origin of life.
The story he wove was quite compelling: that a young Earth accreted about 4.5 billion years ago and was initially bombarded by all manner of debris including planetesimals thus remaining molten during that time. As the bombardment eased, heat radiated away and eventually a thin brittle crust formed, and as the cooling continued water precipitated out of the atmosphere to create the first oceans. Convection of the underlying magma and other forces tore at the thin crust and when this happened under water, the new oceans poured into these rifts and volcanoes and thus began Earth’s first hydrothermal activity.
Corliss believed that hydrothermal vents contained all the conditions necessary for the origin of life on Earth, eliminating the need for specific atmospheric chemistry and energy sources. Miller’s experiments and those that followed him required a reducing atmosphere, where Corliss showed that those conditions occurred naturally in hydrothermal vents. Instead of electrical discharges from lightning, continuous thermal energy was proposed to power those reactions. Raw materials, gases such as methane and ammonia and hydrogen, were all present in these submarine environments. Furthermore, Corliss pointed out that clays found at hydrothermal vents could naturally act as catalysts for reactions, efficiently forming the biological precursor compounds and more complex organic materials.
After Corliss others, such as Gunther Wachtershauser, have built on the hydrothermal vent hypothesis of the origin of life. Wachtershauser, for example, proposed that some early version of biological metabolism predated any form of genetics, and that this metabolism was enabled by conditions at hydrothermal vents. His team and others have claimed to have experimentally confirmed organic synthesis under primordial hydrothermal vent conditions.
What next…
The following table is from a recent review of the origin of life research, and summarizes the early synthesis work including what we discussed above.
There are currently three outstanding theories for the source of complex organic precursors necessary for the origin of life, each of which we touched on more or less:
- Natural synthesis occurring on the early Earth
- Extraterrestrial source from impacting bodies such as asteroids
- Deep-sea hydrothermal vents
There is no way to either exclude or compellingly support any of these hypotheses at this time, so we are at a relative stand-still on that question.
If we agree that the question of deepest origin is too hard, can we query the next step in the evolution of life?
Once the primordial soup or the environment around the deep-sea vent is loaded with precursor organics, how do they self-organize into replicating, metabolizing, identifiable living organisms?
This causes even more hair-pulling and shin-kicking among the normally staid and rational scientific community…
This discussion leads to camps, tribes, factions, outliers... Some champion the need for an informational molecule to precede all the others, perhaps RNA, while even within this camp some say perhaps a different chemistry preceded RNA which then preceded DNA…. Others claim that broad enzymatic requirements for life requires that proteins must have preceded all the other molecules. Yet others demand that metabolism is clearly predominant and without energy there is no life. And some suggest that without a means to separate a living organism from its environment, there can be no life, therefore lipid membranes must have been the first step in the evolution to life.
These are, at the moment, irreconcilable differences, with no means at hand to resolve them or to even move in a given direction.
The search for the origin of life continues today, but draws from all the physical sciences including geology, astrophysics, astronomy, etc. The questions are both broader by looking beyond the Earth to the universe at large for hints of both the precursors to life as well as life itself, and narrower by looking into the quantum mechanics of molecules at the threshold of life. The search for the origin of life here on Earth goes on and we remain no closer to the answer to this day.
The question is indeed, what next?
Thank you!
Again, you have been patient in following me to the end of this very long article with an unsatisfactory “I dunno” at the end.
If you enjoyed this (or even if not), please post it on your social media or forward by email, snail mail, or sign language to whomever and wherever.
Please subscribe if you haven’t already (click on link below) so I can automatically notify you when I post a new article. And check out all the articles on my blog page here: