Nucleotides serve as units of the polymers, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
Both of these acids are essential biomolecules in all lifeforms on Earth.

 

Proteins, DNA, Life in the Laboratory

This is our Second Essay on “Abiogenesis” — The Creation of First Life 

Note to Our Readers:  This is The Second of our three Essays on the Evolution of Life.  Of the three, this Essay is the most technical.  Some readers may elect to skim this Essay or even to skip it.  That’s fine.  We think the reader can move on to Essay #3, which we regard as less technical and more colorful than #2.

The Six Basic Chemical Compounds of Life

In the prior Essay, the first of our three, we discussed the Six Key Chemical Elements of Life – Carbon, Hydrogen, Nitrogen, Sulphur, and Phosphorous.

We know from high school chemistry that chemical elements can combine to form chemical compounds.  In this Essay, we discuss the Six Basic Chemical Compounds of Life, which are: 1

  • Methane (CH4)
  • Ammonia (NH3)
  • Water (H2O)
  • Hydrogen sulfide (H2S)
  • Carbon dioxide (CO2) or carbon monoxide (CO), and
  • Phosphate (PO4).

Note: Molecular oxygen (O2) and ozone (O3), both important parts of today’s atmosphere, were either rare or absent on early Earth. They were created later, in and around the Great Oxygenation Event, which we will take up later in this Book. At the early time of First Life, it is thought that no organisms breathed oxygen as we do today. 2

Organic Compounds

Organic compounds are generally any chemical compounds that contain carbon-hydrogen bonds.

By this definition, methane (CH4) is an organic compound. Most organic compounds arise from biological processes. Methane is a component of natural gas arising from the decomposition of ancient life under the heat and pressure of deep Earth.  Water (H2O) would not be an organic compound, because there is no carbon in it.

Due to carbon’s ability to catenate (form chains with other carbon atoms), millions of organic compounds are now known; most of them manufactured by biochemical systems within living organisms, or by organic chemists making plastics, pharmaceuticals, or petrochemicals (For more, see the Wikipedia article on Organic Compounds.)

Although organic compounds make up only a small percentage of the Earth’s crust, they are of central importance because all known life is based on organic compounds. Living things incorporate inorganic carbon compounds into organic compounds through a network of processes (the carbon cycle) that begins with the conversion of carbon dioxide plus a hydrogen source like water into simple sugars and other organic molecules by organisms using light (photosynthesis) or chemical sources of energy. (See Wikipedia article, “Organic Compound.”)

Still more important for our purposes, are The Four Key Monomer Molecules of Life:

The 4 Key Monomer Molecules of First Life and their Key Processes:

#1.  Lipid moleculesLipid monomer molecules link together to make fats, oils, phospholipids, and waxes. Usually, phospholipids form the cell membrane, the boundary that separates it from the outside world. The membrane encloses and protects the cell’s interior chemistry. The lipids also have other jobs within a cell. Self-enclosure, providing self-identity and self-protection, are a Key Process of life. We discussed these lipid molecules, and the cell membranes they form, at the end of our prior Essay. The remaining three below, are taken up in this Essay.

#2.  Amino-acid moleculesAmino-acid monomers chain together to build the cell’s large protein molecules, which are the workhorses of the cell. The proteins break down food, build up (and constitute) tissues, transport substances, and eliminate waste. Together, those processes are called metabolism. (In addition, the proteins even build the RNA and DNA molecules needed for reproduction.  Metabolism (the ability to take in food, extract energy, and excrete waste) is a Key Process of life.

#3.  Nucleotide moleculesNucleotide monomers combine together to form nucleic-acids. The nucleic-acids form the exceedingly long DNA and RNA molecules that are the self-replicating genetic blueprints that carry the instructions for reproducing new generations of the cell and/or of the organism as a whole. DNA and RNA are self-replicating, organic molecules. The ability to self-replicate, to reproduce, is another of the Key Processes of life.

#4.  Food molecules — In the modern world, the simplest molecules of sugar, the monosaccharides, are the basic cellular food monomers for many organisms, including humans. A prime example is the monosaccharide, glucose. Eating is obviously a Key Processes of life.  At the cellular level, however, “breathing, eating and digesting” are collectively called “cellular respiration.” The cells of other modern organisms also use plants as food for their energy source, but they do it without oxygen in a process called fermentation. Fermentation is a type of anaerobic respiration processes.

Green plants use the process of photosynthesis to make monosaccharides. Then, at night when the sun doesn’t shine, their cells use oxygen to “burn” the monosaccharides as fuel in a process called cellular respiration. Energy moves when monosaccharides such as glucose are oxidized: the glucose molecule gives (“donates”) an electron to the oxygen molecule (which “accepts” the electron, thereby receiving the energy). The green plants can also store the energy in the monosaccharides by assembling them into carbohydrate structures such as cellulose, grains, fruits, nuts, and tubers.

When animals eat the plants (or eat each other), they use the monosaccharides originally stored in the plant structures for fuel, and they can also store them in their own structures including bone, muscle, nerves, and fat. When these processes involve oxygen, they are called aerobic respiration processes.

The cells of other modern organisms also use plants as food for their energy source, but they do it without oxygen in a process called fermentation. Fermentation is a type of anaerobic respiration processes.

Earth is also home to billions of other organisms whose cells do not make or take in molecules of sugar as their basic cellular foodstuff. Instead, and amazingly, they take in minerals like iron or sulfur.  Some of these organisms use oxygen to get energy from the foodstuff (e.g., they “rust” the iron, an aerobic process), and some use non-oxygen (anerobic) processes to release energy from minerals like sulfur.  Whenever any organism takes in “food” at the cellular level, that Key Process is called Cellular Respiration, and it is the “front-end” portion of Cellular Metabolism.

An important take-away is that life has evolved to use many different chemical processes with which to take energy from different kinds of “food.” Life seeks, explores, tries, persists and then life adapts and adopts.  In other words, Life evolves.  And life does all this without any direction or control from a central authority.

More specifically, every living organism is an open energy system that requires a varying set of additional inputs from outside sources: food, water, minerals, and gases found in air or water such as oxygen for animals and carbon-dioxide for green plants. Each of these inputs must be a flow over time because their purpose is to sustain an organism’s life over time.  All these required chemical molecules (which can be simple or complex) ultimately come from non-living Earthly sources. This is persuasive evidence that Abiogenesis on Earth arose from geochemistry.

Among the more than nine million known organic compounds, four major categories of organic molecules listed above — lipids, amino-acids, nucleotides, and the flows of various energy and supplies (e.g., sugars and minerals) — are found in all living things. If we want to describe how life first emerged, we need to describe how each of these four arose, and then we need to describe how they began to work together in the first living cell.

Dr. Hazen writes: “Every life-form consists of discrete assemblages of molecules (cells) that are separated by a molecular barrier from the outside (the environment). These collections of chemicals have evolved two interdependent modes of self-preservation – metabolism and genetics –that together unambiguously distinguish the living from the non-living.” 3

Arvin Ash also agrees, as he says in the first three minutes of his twelve-minute film presentation, “Abiogenesis – How Life Came from Inanimate Matter,” (Sept 7, 2019). And the Wikipedia article on Abiogenesis concurs as well.

In the sections below, we look at each of our “Four Key Molecules of First Life,” and we describe how they emerged naturally from inorganic (non-living) geo-chemistry.

After those sections, we will consider how likely it was for all those monomers to assemble and function together, chemically.

After that, we will talk about the Models of Where, When, and How the Earliest life took place. These models describe the real-world geological forces and locations that brought all the chemistry together.

Apparent Stages in the Origin of Life. 

Unicellular organisms are thought to be he oldest form of life, with early protocells (“before real living cells”) possibly emerging 3.8–4 billion years ago.  4

We take the approach that First Life likely followed a direction of increasing complexity. This direction of increasing complexity would have taken several (likely interrelated and indistinct) steps:

Step #A: The origin of biological monomers: fatty acids, amino-acids, nucleotides, and sugars.
Step #B: The assembly of biological polymers.
Step #C: The evolution from free-floating molecules to membrane-contained molecules.”
Step #D: The interaction of the molecules in working systems of cellular metabolism and reproduction.

Step #A is both a late step in chemical evolution and the first step in biological evolution. It is truly a transition between chemical evolution and biological evolution.  We can almost say that for Steps #B and #C as well. The metabolic and reproduction systems of Stage #D, however, are clearly in the realm of living things. Stage #D is the tough one to trace, containing many interrelationships and many unknowns.

We must note that the traditional four steps listed above may have happened in a different order. For example, the creation of cell membranes in Step #C may well have happened first, since membranes can arise naturally in certain non-living chemical systems. Even more likely is that two or more of these steps took place together, reinforcing each other.

The Origin of Life Requires 3 Kinds of Simple Molecules in the Organism, plus Food Molecules for Energy

To see how Abiogenesis (The Origin of Life) works, we start by breaking it down into its principal components.

Despite the incredible varieties of life that we see today, at the fundamental level, all living things require the four simple molecules listed above, which are called the “Four Monomers of Life.”  (Per Step #A above)

A monomer is a small molecule that becomes a subunit when combined with similar subunits to form larger chains of molecules called “polymers.”

Each of the four Monomers of Life can link together (polymerize) to form large macromolecules called lipids, amino-acids, and nucleotides. These macromolecules are typically composed of thousands of atoms. (Carbohydrates, a food/energy source, are also macromolecules.) wiki on macromolecule]

We already discussed Key Molecule #1 – “Lipids” and cellular membranes at the end of our last Essay. We also talked about non-living systems that seem structurally analogous to lipids – sea foam and geode crystals.  Lastly, in First Essay we went on to look at diatoms and seashells, which are non-living mineral creations of life.

Key Molecule #2 in Creating Life – Amino-acids: How a Cell Does Its Work

Now we turn to the second of Four Key Components of Abiogenesis (the Origin of Life), which are amino- acids. Amino-acids can chain themselves together to build the cell’s large protein molecules, which are the workhorses of the cell.

The key elements of an amino-acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino-acids. About 500 naturally occurring amino- acids are known and they can be classified in many ways. 5

Short chains of amino-acid molecules are called peptides, and a polypeptide is a longer chain of between 15 to 50 amino-acids.

The amino-acids are the cell’s builders – they make the proteins.  The amino-acids and the proteins do most of the work in the cell, principally including its metabolism.

As the main part of proteins, amino-acids are the second-largest component (water is the largest) of human muscles and other tissues. 6

Beyond their role in proteins, amino-acids participate in a number of processes such as transmitting nerve signals and in building complex molecules out of simple ones (biosynthesis).

Proteins

A polypeptide that contains more than approximately 50 amino-acids is known as a protein. Proteins consist of one or more polypeptides arranged (‘folded”) in a biologically functional way. 7

In modern cells, proteins are formed within tiny cellular “machines” called Ribosomes, which we will discuss more fully a bit later.

The proteins break down food and build up tissues. They are used for structural support, storage, transport, cellular communication, response to stimuli, movement, defense against foreign substances, and elimination of waste. Together, most of these processes are part of the grand process called cellular metabolism. The proteins even build the RNA and DNA molecules needed for reproduction. (See the Wikipedia article on Amino-acids.]

Protein Folding

Each protein exists first as an unfolded polypeptide, after being translated from a sequence of Messenger RNA into a linear, loosely coiled chain of amino-acids. At this stage, the protein polypeptide lacks any stable (long-lasting) three-dimensional structure.

The folded structure of a myoglobin Protein

A protein isn’t functional until it has been folded from a random-coil shape into its native three-dimensional shape. It is the three-dimensional shape that is able to present a certain surface that “fits with” the shape of another molecule. Only when the fit is accomplished can the intended biochemical process move forward.  8

Note the similarity between protein-folding and the way that mineral crystals naturally grow.  It is also analogous to the way that silicate-clay crystals can act as templates for the formation of biomolecules, as we discuss below in our section on The Silicate-Clay Model cellular evolution.

Large catalytic molecules called chaperones assist protein folding. This fact further supports the argument that life evolved naturally from non-living (inorganic) chemistry.

Protein Crystals

Interestingly, proteins can take on crystalline structures. [See my image in Photos file.]  The “chaperone” molecule just mentioned is itself a huge crystalline structure.

Crystalized Proteins

Prions – Misfolded Proteins.

Prions are misfolded proteins with the ability to transmit their misfolded shape onto normal proteins. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It is not known what causes the normal protein to misfold, but the abnormal three-dimensional structure is suspected of conferring infectious properties, collapsing nearby protein molecules into the same shape. 10

Prions can form abnormal aggregates of proteins called amyloids, which accumulate in infected tissue and are associated with tissue damage and cell death. Amyloids are also responsible for several other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. 11

Were Amino-acids the First Key Molecule to Evolve?

Many scientists hold that the amino-acids and proteins evolved before “Key Molecule #3,” the nucleotides.  This view is sometimes called the “Protein-World Model,” which can be paired with the “Warm Little Pond Model.” A more recent and more accepted model is that the Nucleotides and RNA evolved first, i.e., before the amino acids.  It is also possible that amino acids and RNA coevolved together.  We will discuss these and other models later in this Essay.

Darwin’s Conjecture

In an 1871 letter to Joseph Dalton Hooker, Charles Darwin proposed a natural process for the origin of life. Darwin suggested that the original spark of life may have begun in a “warm little pond,” with all sorts of ammonia and phosphoric salts, lights, heat, electricity, etc. Darwin further proposed that a protein compound would then be chemically formed ready to undergo still more complex changes. 12

Modern living things, both animals and plants, require oxygen to “burn” their cellular food (sugars) and thus obtain their energy. However, today’s atmospheric oxygen would have “burned away” any synthesis of Earth’s first organic molecules, which are the building blocks of life. Therefore, it has long been thought that early Earth had a “reducing” atmosphere, meaning it contained almost no oxygen. Instead, it was made up of gases such as hydrogen, carbon monoxide, methane, and hydrogen sulfide.

The Miller-Urey Experiments – 1950’s

In the 1950’s, several experiments by Drs. Stanley Miller and Harold Urey verified that the natural formation of organic molecular compounds was possible under the oxygen-less atmospheric conditions of the primordial Earth. These compounds included amino acids, which are the components of proteins. 13

Their experiments used water (H2O), methane (CH4), ammonia (NH3), and hydrogen (H2). The chemicals were all sealed inside a sterile 5-liter glass flask connected to a 500 ml flask half-full of water. The water in the smaller flask was heated to induce evaporation, and the water vapor was allowed to enter the larger flask. Continuous electrical sparks were fired between the electrodes to simulate lightning in the water vapor and gaseous mixture, and then the simulated atmosphere was cooled again so that the water condensed and trickled into a U-shaped trap at the bottom of the apparatus. 14

The liquid in the Miller-Urey U-shaped trap contained three experiment-produced amino-acids that are common in living things. Early Earth would have had all three of them. In fact, these basic building blocks now appear to be common throughout the universe, as we will discuss later in our section on Panspermia.

Societal Reactions to The Miller-Urey Experiment

Societal reactions to the Miller-Urey experiment varied widely. On the one hand, religious Fundamentalists looked at Miller-Urey’s results and said, “Okay, they got a few amino-acids, but how did but how did the myriad of amino-acid molecules in a living cell come about?  They can’t explain that; therefore, God must have created them.”

On the other hand, Scientists said, “Okay, Miller and Urey successfully produced a few amino-acids, but how did the myriad of known amino-acid molecules come about?  Let’s study chemistry and biology further and see if we can eventually explain it; and in the meantime, we can put forward plausible models of it that can guide our further investigations.”

These two types of reactions are still applied today, and not just to the question of Life’s origin, but scientific progress of all kinds, including the origin of Earth and the origin of human beings.

Updating the Miller-Urey Experiment – 1960’s

The Miller-Urey experiment did inspire many others. Notably, professors Juan I Oro and A.P. Kimball found that many amino-acids are formed from HCN and ammonia under these conditions. 15

Updating Miller-Urey -to 2008

In 2008, a group of scientists examined 11 vials left over from Miller’s experiments of the early 1950s.

By using high-performance liquid chromatography and mass spectrometry, the group found more organic molecules than Miller-Urey had found. They found that Miller’s volcano-like experiment had produced the most organic molecules — 22 amino-acids. As Arvin Ash has said, “It turns out it’s pretty easy to form a number of organic molecules in a wide range of environments.” 16

Key Molecule #3 in the Origin of Life – Nucleotides

The nucleotides are our third “Key Monomer.”  Nucleotides are the simple molecules (monomers) that join to make the long molecular chains (polymers) named nucleic-acids – specifically, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).  A single DNA polymer molecule contains all an organism’s hereditary information, its genetic code – the entire blueprint for building its structure and systems. An RNA molecule is a DNA molecule “split lengthwise down the middle.”

Nucleotides are composed of carbon, oxygen, hydrogen, and phosphorous. These chemical elements – C, O, H, & P — are the same as the elements that make up amino-acids, except that nucleotides have added phosphorous.  (Biochemists usually say that nucleotides consist of three “sub-units” of chemical elements: a sugar, a nitrogen base, and a phosphates group.)

Just as important as the addition of phosphorous is the fact that the molecules in nucleotides are arranged in different patterns from the molecules of amino-acids. Their different three-dimensional shapes or patterns allow them to do different jobs inside the cell.

The nucleic-acids DNA and RNA are found in abundance in all living things. Inside each organism, they encode, store, and transmit the distinct design information of that organism. They also transmit and express that information to the interior operations of the cell, as well as to the next generation of the organism.

The DNA polymer molecule, often described as a “double-helix,” looks like a spiral ladder with a great many “rungs.” Strings of nucleotides are bonded to form the long twisting “rails” of the ladder.

Running between the two spiraling rails are the “steps” of the ladder. Each step is composed of a base-pair of nucleotides selected from an inventory of five different nucleotides — adenine, cytosine, guanine, thymine, and uracil.  Each base-pair step in a DNA ladder is composed of adenine-thymine (AT) or guanine-cytosine (GC). Each base pair in an RNA half-ladder is composed of adenine-uracil (AU) or guanine-cytosine (GC). These base pairs are the foundation of the “genetic code” that is woven into the DNA of all living things. (See the Wikipedia entries for Nucleic Acid Notation and Genetic Code.)

How RNA Passes Genetic Information to a New Generation

If a DNA molecule is alternatively pictured not as a spiral ladder, but as a long “twisted zipper,” an RNA molecule can roughly be thought of as an “unzipped half” of a DNA molecule.

When a DNA molecule unzips, and becomes two strands of RNA, each strand picks up free-floating nucleotides and attaches them to make the half-steps of the partial ladder into full steps. Then a new ladder rail is added, joining up outer ends of all the steps. In this manner, the original DNA ladder is replaced by two new DNA ladders. Then the cell divides into two new cells, each with its own double-helix ladder.

The codes in the DNA and RNA molecules are determined not by the nature of the chemicals in the DNA or RNA molecules, but by the order of the steps in those molecules. The order makes the code, just as the order of letters makes the words of a language, and the order of zeros and ones makes the code of a computer program. 

Related Terminology:  A genome is an organism’s complete set of DNA. If we think of an organism’s DNA code as its complete “manual of written instructions,” then we can say those instructions are carefully organized into “chapters” (chromosomes), which are then organized into “paragraphs” (genes). The entire manual from start to finish would be the genome. Almost every creature’s genome, chromosomes and genes are organized in the same way.

Crystalized DNA

Earlier, we remarked that proteins can assume a crystalline form. DNA, the long twin-ladder molecule that contains our genetics code, can also be a crystal.  “DNA crystals form when a double helix is suspended in liquid that evaporates. They grow in patterns dictated by the information stored within the strands. Seen in cross-polarized light, they display a mind-bending kaleidoscope of color and shape.  The huge range of crystal structure is amazing.” 17

How RNA Passes Construction Information for Making Amino-acids

We’ve said that DNA contains all the genetic information of an organism and passes it on to the next generation. Just as importantly, inside each organism, the long RNA half-ladder also delivers genetic “blueprints” directing the cell how to make its own amino-acid building blocks. The cell does this by passing RNA “blueprints” to the cell’s ribosomes, which are the “molecular machines” that build amino-acids. The RNA that does this delivery work is called “messenger RNA” (mRNA).

The human genome (23 chromosomes) is estimated to be about 3.2 billion base-pairs long and to contain 20,000–25,000 distinct protein-coding genes. 18

The Origin of Nucleotides

So, how did nucleotides originate?  And which came first, the amino-acids or the nucleotides? Science continues to pursue the answers to these questions.  We don’t yet have answers, but we do have models that are supported by scientific evidence.

The nucleotides that make the nucleic acids DNA and RNA appear to be products of evolution.  It is believed that the first nucleotides, like the amino-acids, emerged in the “primordial soup” – perhaps a pond on Earth’s surface (with or without a lightning strike), or possibly in an area of water around a hot or warm sub-sea hydrothermal vent.

Today, the RNA-World Model (i.e., RNA-World Hypothesis) is ascendent because many scientists think that the nucleotides, chained together to form RNA (a simpler form of DNA), could have originally performed both functions – protein building and genetic coding. 

The Joan Oró i Florensa Nucleotide Experiments – 1960’s

In the 1960’s, the previously mentioned experiments conducted by teams led by Professor Joan Oró i Florensa found that  RNA and DNA nucleobases could be obtained through simulated prebiotic chemistry with an non-oxygen, i.e., a reducing, atmosphere. For example, Dr. Oró found that the nucleotide base adenine could be made from hydrogen cyanide (HCN) and ammonia in a water solution.

The Georgia Tech Nucleotide Experiments — 2016

Experimental studies led by Nicholas V. Hud of Georgia Institute of Technology (GIT) in 2016 showed that plausible proto-nucleotides can be formed in simulated early Earth environments. 19

The Georgia team reported that the nucleotides they produced can form base pairs similar to the modern DNA base-pairs (adenine, cytosine, uracil, and guanine) that are formed by modern nucleic acids. Furthermore, these experimentally-produced nucleotides can self-assemble into large, stacked, noncovalent complexes, which could eventually facilitate the formation of RNA-like molecules.

Dr. Hud contends that such molecules could have later evolved to incorporate the bases now found in RNA. 20

The Czech Nucleotide Experiments – 2017

Recall that in our recent section on the emergence of amino-acids, we described the Miller-Urey experiment done in the 1950’s. Originally, The Miller-Urey experiment was thought to produce only amino-acids.

However, a 2017 study by researchers in the Czech Republic has shown that a modified version of the original experiment produces nucleotides as well as amino-acids.

Their experimental setup was similar to the original Miller-Urey experiment, using a simple reducing mixture of NH3 + CO and H2O. But in addition to electric discharge in water vapor, the Czech team also subjected the solution to powerful laser discharges to simulate the plasmas resulting from asteroid impact shock waves.

The results of the experiment demonstrated that all RNA nucleobases were synthesized, strongly supporting the emergence of biologically relevant chemicals in an Early Earth atmosphere. 21

Ribosomes – “Tiny Cellular Machines”

Now we want to take a moment to discuss ribosomes, because in modern cells they work in between our first key molecule, amino-acids, and our second key molecule, nucleotides.  More specifically, ribosomes are mostly made out of RNA, while on the other hand they make (manufacture) most amino-acids.

For decades now, it has been firmly established in biology that protein catalysis (the work of building proteins) in modern cells is reserved for special molecules called enzymes located in the ribosomes. The “blueprints” or “catalytic templates” used by the enzyme molecules, are segments of genetic nucleotide chains messengered out of the nucleus as messenger-RNA (mRNA). Each ribosome is a tiny cellular machine that moves along a particular segment of the mRNA, using that segment’s sequence of genetic information as a template to manufacture a particular amino-acid. It is as if the ribosome were “reading” the RNA sequence “by braille.” 22

Note: Catalysis is the process by which a substance speeds up a chemical reaction without being consumed or altered in the process. Substances that can accomplish this remarkable feat are termed catalysts and are of immense importance in chemistry and biology. In biology, sequences of amino-acids compose the enzymes with the aid of catalysts.  https://www.britannica.com/science/catalysis/Biological-catalysts-the-enzymes.

It is important to know that catalysis also happens quite often in non-living (inorganic) chemistry. This is yet another piece of clear evidence showing that the cellular processes of life arose naturally from the processes of standard inorganic chemistry. Supernatural intervention is not required.

Since ribosomes are not surrounded by a membrane, they are not organelles like the much larger nucleus and mitochondria are. Ribosomes are simple cell inclusions, as are pigment granules, fat droplets, and nutritive substances. Ribosomes are found in large numbers in the cytoplasm of living cells.

As we discussed earlier, the amino-acids made in this manner build the structure and conduct the operations of most chemical processes inside the cells of all life forms.

Cellular Machines and Structural Cell Biology

Modern ribosomes are an example of “cellular machines.” Cellular Machines are multi-component macro-molecules that carry out essential biological processes inside individual cells. Another type of cellular machine are the macro-molecules that make the little tails (flagella) that certain bacteria use to propel themselves through the water. There are hundreds of types of cellular machines at work inside cells.

The ability of electron microscopes to see the atomic structures of molecules has led to the new field of Structural Cell Biology. Powerful microscopy plus crystallography and computational tools are now able to generate testable atomic models of cellular machines. 23

Synthetic Biology

Another new field, Synthetic Biology, uses our understanding of cellular machines and other aspects of cellular biology to engineer new functions into living things, producing useful chemical compounds such as pharmaceuticals and biofuels. “This effort has already led to some astonishing successes, but much work, including standardization of techniques for manipulating genes, still needs to be done before cells can be as easily engineered as traditional machines.” 24

Synthetic Biology Creates a Vaccine for the Covid-19 Virus

In late 2020, synthetic biology successfully produced some of the first vaccines to fight the COVID-19 virus. Unlike traditional vaccines which use weakened or inactivated versions of the germ they intend to fight, the new vaccines use laboratory-made mRNA.  When injected into our arms, the new mRNA vaccines instruct some of our cells to make a harmless piece of “spike protein” on their own surfaces, like the spikes found on the surface of the COVID-19 virus. Next, our bodies’ overall immune systems recognize the spiky proteins as “foreign bodies,” and our immune systems begin making antibodies to kill the cells that have spikes. At the end of the process, our bodies have learned how to kill any and all cells that have spikes, thus protecting us against future infection from real COVID-19 viruses. 25

We have now described the first three of the four monomers that are key in starting life – lipids, amino-acids, and nucleotides. It is remarkable that all three are mostly composed of oxygen, hydrogen, nitrogen and carbon (plus a bit of phosphorous in the third of them). The different characteristics and powers of these molecules lie in how those chemical elements are arranged and connected.  As we say repeatedly in the Book of Continuing Creation, the key to creation is the combining of components to create wholes that are remarkably new and different. 

Before we talk about Key Molecules #4 – the “food” molecules, we should ask if “self-replication” or “reproduction” ever occurs outside of life, in the realm of inorganic chemistry. 

Self-replication Among Non-Living (Inorganic) Chemicals

While DNA and RNA are both organic molecules that can self-replicate, all the other organic molecules need help from adjacent molecular machinery. For example, amino-acids get replicated, but only at the direction of RNA (an “unzipped” half of DNA), as we just discussed.

However, there are examples of chemical molecules self-creating outside of living organisms.  Here are two of those examples:

Example #1 — “Life makes more of itself. And now, so can a set of custom-designed chemicals. Chemists [Gerald Joyce and Tracey Lincoln] have shown that a group of synthetic enzymes replicated, competed, and evolved much like a natural ecosystem, but without life or cells… The researchers began with pairs of enzymes they had been tweaking and designing for the past eight years. Each member of the pairs can only reproduce with the help of the other member.” From there, Joyce and Lincoln added the enzymes into a soup of building blocks, “short strings of nucleic bases….and tweaked them to find the base pairs [that would allow the enzymes] to reproduce…. When the scientists put them in a bigger soup mix, a new set of mutants emerged that were better at replicating within the system. It worked almost like an ecosystem, but with just straight chemistry.” 26

Example #2 –“Although self-replication is usually associated with DNA, the behavior has been seen in very different-looking chemical systems – for example in rotaxanes [tiny molecular assemblies shaped like ring around an axel, where the axel is capped at each end to keep the ring from sliding off]. This raises the intriguing possibility of creating completely synthetic lifeforms that tick all three boxes for life: replication, the use and storage of energy to perform… reactions that require outside energy, while keeping all of these functions contained to protect them from parasitic lifeforms.” 27

Key Requirement for Life #4 – Food (“electron donors”) for Energy

This brings us to the fourth of Four Key Components of the Origin of Life (Abiogenesis), which are the various molecules that cells bring in from outside to fuel the cell’s housekeeping, repair, and construction. In other words, we are talking about “food” molecules, water, and often (but not always) some gas such as oxygen or carbon-dioxide from the sea or from the air.

Let’s start by looking at what we humans (giant multi-celled creatures composed of trillions of cells) take in on behalf of our individual cells.  We take in (eat) food, we take in (drink) water, and we take in (breathe) oxygen from the air. All three of those inputs go into our bloodstream, which delivers them to our individual cells.

The food, of course, must first be broken down in our stomachs and intestines, because it has to be turned into simple molecules that the individual cells can handle.  An important and common molecule is the simple sugar, glucose.

Cellular Respiration and Cellular Metabolism

When one of our human cells takes in oxygen (O2), water (H2O), and glucose (C6H12O6), this process is called Cellular Respiration. In fact, when the cell of any organism, unicellular or multicellular, takes in its “life supplies,” no matter what those supplies are, the process in called Cellular Respiration. 28

When any sort of cell uses its inputs to do work – repairing, growing, transporting, moving, reproducing – that process is called Cellular Metabolism. Cellular metabolism also includes the processes by which energy is stored in body tissues for later use by the organism.

Metabolism is a Process, but not a process of Evolution. It is a process of homeostasis, of survival, of continuing life within each organism. (For more, see our Essay, The Processes of Evolution and Their Spiritual Meaning.)

Note: While lungs and gills are sometimes said to do “respiration” for animals, here in this section we are talking about cellular respiration. And while every human being is said to have an overall “metabolism,” here we are talking only about cellular metabolism.

Aerobic (“uses oxygen”) Cellular Respiration

Cellular energy powers the cell as it performs all its metabolic activities. Cellular Respiration is the set of processes that take in food and releases its energy; it is the “front-end” part of metabolism.

There are two types of respiration: Aerobic respiration, which uses oxygen; and anaerobic respiration, which does not use oxygen.

In aerobic cellular respiration, oxidation of organic “food” compounds takes place in cell cytoplasm to produce energy. After respiration, the energy eventually goes into molecules of adenosine triphosphate (ATP). ATP is the “quick-storage” of energy that is immediately ready for use by muscle, nerve, and all other cells.

To see how the aerobic respiration chemistry works, we will use glucose (the most abundant of the simple sugars) as our example of a food (fuel) molecule.

When we humans take in oxygen, we use it to accept electrons “donated” from our food atoms. In the aerobic respiration process, the glucose (cellular “food”) is oxidized (“burned”). This oxidation of glucose releases chemical energy for the cell to use.  In chemistry, this is an example of a “Redox Reaction:”

6 Glucose+ 6 Oxygen yields 6 Carbon-dioxide + Water + energy

C6H12O6 + 6O2 à  6CO2 + 6H20 + energy

In this reaction, Glucose donates the electrons and Oxygen accepts the electrons.

(See Khan Academy, “Introduction to Cellular Respiration and Redox.”)

It is called a “redox” reaction because the glucose (a simple sugar monomer) is “oxidized” to carbon dioxide. The “acceptor molecule” for the electrons is oxygen, which becomes “reduced” to water. When the chemical bonds of the glucose molecule are broken, electrons move, releasing chemical energy (a form of electromagnetic energy) for the cell’s use. (Often, the cell will temporarily hold the energy in the “quick storage” form of ATP.)

Humans have an intuitive understanding of oxidation because we have seen fires use this process to burn paper and wood since we were children.  Oxidation produces heat because the chemical bonds in the fuel contain more energy than the bonds in the water and carbon dioxide that are the end-products of combustion.

Note — Below is more detailed biochemistry nomenclature for readers who have an interest:

A “Redox (Reduction-Oxidation) Reaction” between two participants in a chemical reaction that involves the donation of electrons (energy) by one of the participants to the other. (Participants may be chemical elements or chemical compounds.)

The term “Oxidation” refers to the participant element that donates electrons (energy). The term “Reduction” refers to the element that accepts the electrons (energy).

An example of a Redox Reaction is when pure iron reacts with oxygen, forming iron-oxide compounds such as rust and iron ores. The iron is “oxidized,” and the oxygen is “reduced.”

A blast furnace in a steel mill reverses that reaction, using carbon monoxide as a reducing agent (it accepts electrons and becomes Reduced) to reduce the iron-oxide ore (it donates electrons).

( See https://simple.wikipedia.org/wiki/Reduction_(chemistry) )

Anaerobic (“doesn’t use oxygen”) Cellular Respiration

While our human cells get their energy through oxidation, that’s not how most scientists think the proto-cells and the cells of First Life got their energy. Why? Because early Earth had little or no oxygen in its atmosphere or in the oceans.

Instead, the primordial atmosphere was mainly composed of gases spewed from volcanoes. The atmosphere included hydrogen sulfide, methane, hydrogen, and ten to 200 times as much carbon dioxide as today’s atmosphere. 29

Readers will recall that the Miller-Urey’s experiment used a glass vessel containing a similar (but not identical) “atmosphere” composed of water (H2O), methane (CH4), ammonia (NH3), and hydrogen (H2). 30 Whatever the actual mix, the early atmosphere was exceedingly hot. Any oxygen that had been present would have soon be used up by burning away many of the more populous hydrogen and hydrocarbon molecules.

This early atmosphere is quite suitable for organisms that do a different type of cellular respiration, namely   non-oxygen using anaerobic respiration.  We know this type of respiration was possible, because this method is still used today by many unicellular organisms, principally Archaea, that often live in unique sheltered environments where oxygen is either rare or not present at all. These modern environments include swamps, undersea hydrothermal vents, and sulfurous surface geysers like those at Yellowstone. https://en.wikipedia.org/wiki/Anaerobic_respiration

Most scientists think that Earth’s First Life, the Last Universal Common Ancestor,” had an anerobic (non-oxygen using) metabolism like so many of today’s archaea have. Today’s archaea would be descendants of that Original Ancestor. Of course, all of today’s aerobic (oxygen using) organisms would also be descended from that same Original Ancestor, but first they had to evolve an oxygen-based metabolism. Shortly, we will talk about how that evolutionary switch most likely happened.

Anaerobic respiration usually means that elements other than oxygen are the electron acceptors. Common replacements for oxygen are nitrates, iron, manganese, sulfur, sulfates, fumaric acid and carbon dioxide. These electron acceptors have lesser ability to accept electrons than oxygen has. Since fewer electrons travel, less energy is released per each reaction. Anaerobic respiration is therefore less efficient than aerobic respiration; except, of course, when oxygen is scarce.  31 When oxygen did become prevalent on Earth, many ancient single-celled organisms evolved the ability to use aerobic metabolism – because it is much more efficient. 

An Example of Early Anerobic Respiration

For purposes of illustration, let’s say that the First Cell (or even the first protocell) consumed raw, elemental Sulfur and used it as its electron acceptor.  If so, then Hydrogen was likely used as the electron donator.

Note: Although sulfur is primarily found in sedimentary rocks and sea water, it is particularly important to living things because it is a component of many proteins. 32

“Sulfur-eaters” – Anaerobic Respiration of Sulfur

Here is the equation for the anaerobic respiration of Sulfur by Sulfur-reducing microorganisms:

Hydrogen + Sulfur yields Hydrogen-sulfide

H2 + S yields H2S

Hydrogen is the “food” or “fuel” that is donating electrons, and Sulfur is the electron acceptor.

Since Sulfur has accepted electrons, the Sulfur has been “reduced.”

Note that since oxygen is not involved, this is not a “redox reaction.” Instead, it is called a “sulfur-reduction respiration,” and is the “front door” to “sulfur-reduction metabolism.”

In our example, the end-product, Hydrogen-sulfide (H2S), is a gas having the foul odor of a rotten eggs. Several types of bacteria and many archaea can reduce elemental sulfur. 33

Similar microbes use inorganic sulfur compounds, such as Sulfide (SO3) and Sulfate (SO4), as electron acceptors. Sulfur and sulfate-reducing microorganisms can be traced back to 3.5 billion years ago and are among the oldest forms of microbes.35

Today, many species of archaea and bacteria still use reduction reactions to survive and grow. We know them colloquially as sulfur-gas “breathers” “iron-eaters,” and similar names. Of course, since these microbes have neither mouths nor lungs, they don’t really “eat” or “breathe.” The most correct expression would be to say they “consume,” or “take in” the chemical compounds they need to live. Sulfur-based metabolism has been found largely in microorganisms from extreme environments, and previously unknown microorganisms found there in recent years. 36

Elemental sulfur and sulfates remain abundant in the modern world, especially in and around deep-sea hydrothermal vents, hot springs, and other extreme environments.  In July 2019, a scientific study of Kidd Mine in Canada discovered sulfur-breathing organisms which live 7900 feet below the surface, and which “breathe” sulfur in order to survive. These organisms are also remarkable due to consuming minerals such as pyrite as their food source. 37

Anaerobic Respiration of Organic Foods

Microbes also anaerobically take in organic foods – such as grains, grapes, dead plants and animals. The ones that “eat” grape and grain sugars use the anerobic process fermentation, which has alcohol as a by-product. (Yeast, which is a microbial fungus, can also do this.) The microbes that “eat” dead swamp plants and landfill garbage often have smelly hydrogen sulfide gas as a by-product, as well as methane (from which they get the name methanogens). There are even bacteria in the human gut which use anaerobic chemistry to help us digest our food.

But these food types are organic, i.e., they were produced by other living things, and so it is chronologically impossible for them to have been First Life.  By definition, “First Life” had to get its nourishment from non-living, inorganic sources.     

Note: In many animals, including humans, a molecule of glucose, usually metabolized aerobically, can also be respirated anaerobically, when there is no oxygen available in the blood.  But the anaerobic path only produces one-third the energy (measured in molecules of adenosine triphosphate, ATP) as the aerobic path. ATP molecules are what directly fuels our cells. Also, the anerobic path produces lactic acid instead of water and carbon-dioxide; and in animals, lactic acid can cause painful muscle cramps. Lastly, anaerobic metabolism can only use glucose and glycogen, while aerobic metabolism can also break down fats and protein. 38

To gain increased energy-efficiency, organisms eventually evolved the ability to use aerobic respiration. The aerobic pathway enabled them to access and deploy energy more efficiently. But the aerobic path of evolution wasn’t possible until Earth’s ocean had enough free oxygen (O2) dissolved in it, and/or Earth had enough free O2 floating in the air, to make aerobic respiration possible. That great increase in O2 was made possible largely by the cyanobacteria, which we will discuss in our following (as yet unwritten Essay), The Rise of Multicellular Life.

It is important to understand that multicellular animals, including humans, make good use of the “triple energy” they get from the aerobic respiration of their food. They (we) use much of the energy for locomotion. Animal creatures can swim, crawl, walk, climb and swing, glide, and fly.  We do this to hunt for food, escape predators, outrun natural disasters, and to escape wars and other forms of adverse competition.  (Of course, many bacteria and protists also move around, but not as much as most animals do.) We will take up the Evolution of multicellular life in our next Essay.

To Summarize, what can we say about the creation of the four Key Molecules of Life? 

Here’s what Professor Hazen wrote in 2012 about his work with the Carnegie Institution (and sponsored by NASA) to create the Four Monomers of Life in the laboratory:

“Our results, now duplicated and expanded in numerous labs, show beyond a doubt that a suite of life’s molecules can be synthesized easily in the pressure-cooker conditions of [Earth’s] shallow crust.  Volcanic gases containing carbon and nitrogen readily react with common rocks and seawater to make virtually all of life’s basic building blocks…“What’s more, these synthesis processes are governed by relatively gentle chemical reactions [oxidation and reduction] reactions, similar to the familiar rusting of iron… These are the same kinds of chemical reactions that life uses in metabolism…” — Professor Robert Hazen 39

If the Carnegie Institution’s results continue to be confirmed, they provide strong support for the “Deep-Hot Model” of the Origin of Life. We will talk more about that model (and other models) later in this Essay.

How the Four Key Molecules Work Together

This is the section where we talk about how all 4 of the Key Monomers — the lipids, amino-acids, nucleotides, and the various food molecules evolved to work together to make the First Living Organism.

Many scientists think that inside the earliest functioning cells, the “protocells,” the second and third of our Key Molecules, i.e., the nucleotides and the amino-acids, worked together using a simpler version of DNA, namely Messenger-RNA (mRNA), to do two important jobs: (1) store and transmit genetic information, and (2) direct the construction of amino-acids.

This has become an important hypothesis of the Origin of Life called the “mRNA Model,” or simply as the RNA World Model.

The “RNA-World” Model

In modern living things, RNA is created from DNA when the DNA “unzips” down its long center to form two strings of RNA. Then, segments from one of the halves, Messenger-RNA (mRNA), travel to the cell’s ribosomes and give them the “blueprints” for specific proteins. Lastly, special enzymes in the ribosomes manufacture the proteins.

The mRNA Model points out, however, that there likely were no ribosomes at the time of the protocells, because ribosomes are quite complex.  Instead, the Model argues that the mRNA did both the work of modern DNA and the work of modern ribosomes.

Since RNA is simpler than DNA, model proponents think the first RNA likely evolved before the first DNA. This idea is central to the widely accepted “RNA-World Model” (i.e., RNA-World Hypothesis). The Kahn Academy has an excellent online lesson and written presentation about “RNA World.’ Go to: https://www.khanacademy.org/science/ap-biology/natural-selection/origins-of-life-on-earth/a/rna-world

In 1982, it was discovered that the simpler (“unzipped”) half of DNA, called RNA, is capable of doing, alone, both of these two jobs:

  1. RNA can store and carry the genetic instructions for the next generation, and
  2. RNA can also direct the protein manufacturing work that enzymes now do in modern organisms. 40

This discovery led Professor Walter Gilbert of Harvard to propose, in 1986, that in the distant past, Earth’s first cells used RNA as both genetic material and as the catalytic protein-constructing molecule, whereas in modern cells these functions are divided between DNA and ribosomal enzymes.

To repeat, the RNA-World model also argues that life on Earth began with a simple RNA molecule that could copy itself without help from other molecules. “RNA-World” is a hypothetical early stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA.

Because early RNA is now thought to have done both these jobs – manufacture proteins and pass genetic information on to the next generation — most scientists think life as we know it began in an RNA-World; a world which at first had no DNA or proteins even in it. 41

It is proposed that the first strands of RNA likely weren’t very stable and degraded quickly. But some were more stable than others; these more-stable strands grew longer and bonded nucleotides more quickly. Eventually, RNA strands grew faster than they broke down—and this was RNA’s foot in the door. Over millions of years, these RNAs multiplied and evolved to create an array of RNA machines, including ribosomes, that are the basis of life as we know it today. 42

Of course, alternative chemical paths to original life have been proposed. 43  Even so, the evidence for an early RNA-World Model is strong enough that the hypothesis has gained wide acceptance. 44

How and Why Did Ribosomes Evolve?

If early RNA could make amino-acid molecules by itself, how and why did ribosomes evolve?

Scientists who support the RNA-World model think that the ribosome may have first originated as a complex of self-replicating RNA. Only later, when amino-acids began to appear, did that complex evolve the ability to synthesize proteins. The early ribosomal RNA was able to take on the task of amino-acid synthesis because it already had the informational, structural, and catalytic functions that it needed to do this work efficiently 45

But for RNA molecules to take hold, they would have needed an abundant supply of nucleotides, and scientists think that nucleotide-building RNAs evolved to provide these RNA building blocks. 46

The enzymes that now make protein inside ribosomes may have come to replace RNA-manufacturing because the enzymes came to be more abundant and versatile. This is supported by the fact that the ribosomes’ own structure contains characteristics from both nucleotides and amino-acids. 47

How and Why Did DNA Evolve?

Why did DNA evolve to replace RNA as the safe-keeping molecule for genetic information? Well, DNA has better stability and durability than RNA, and this alone may explain why it became the predominant information storage molecule in all modern organisms. 48

Note: Sometimes, the term “RNA-World” is used to refer to the entire modeled chain of evolution, from the first nucleotide to RNA, to Ribosomes and proteins, to DNA. Among other things, this overall model explains how nucleotides and RNA on the one hand, evolved to work together with amino-acids, and proteins on the other hand; all resulting in the grand configuration of interlocking systems we see in modern living cells.

Many of the steps or links in the RNA-World model have not yet been fully explained and await additional research. They will be difficult to nail down because the earliest living cells on Earth left no fossil record.

There are more than three million differences between your genome and anyone else’s. On the other hand, we are all 99.9% the same, DNA-wise. (By contrast, we are only about 99 percent the same as our closest relatives, chimpanzees.) 49

Twenty-first Century Efforts to Create First-Life in the Laboratory

Early in the twenty-first century, research groups have already determined ways of creating rudimentary versions of cellular metabolism; and of transplanting hand-crafted genomes into living cells.

In 2009-10, Professor Gerald Joyce’s laboratory at the Scripps Research Institute, produced a self-sustaining and self-replicating chemical system in glass containers (in vitro).  Moreover, this system was capable of exponential growth and it featured changing proportions of the original chemicals.

However, all of Dr. Joyce’s new chemical molecules were exact copies of the old molecules, so there was no evolution of novelty; no ability to mutate. The system could not combine those chemicals in new ways to adapt to changes in its environment; it could not evolve50

In September 2017, researchers from 17 laboratories in the Netherlands formed the group, Building a Synthetic Cell (BaSyC), which aims to construct a “cell-like, growing and dividing system” within ten years, according to biophysicist Marileen Dogterom, who directs BaSyC and a laboratory at Delft University of Technology. The project is powered by a $21.3 million Dutch Gravitation grant. 51

As of 2018, various laboratories around the world have successfully done several things:

  • Artificially produced cell-like lipid microspheres and micro-injected them with amino-acids;
  • Made a rudimentary artificial mitochondrion (a cellular machine that manufactures the ready-energy ATP molecules that provide ready energy on demand quickly power to muscles);
  • Isolated 17 natural enzymes from 9 different organisms that together can do photosynthesis more simply and efficiently than real photosynthesis can;
  • Isolated a relatively small number of the most critical genes from a simple bacterium and had that “minimal genome” boot-up a free-living, slow-growing organism. 52(End of this Essay.  Footnotes follow below:)

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Footnotes to this Essay:

  1. From the Simple Wikipedia article on “Origin of Life.”
  2. J.F. Kasting, “Earth’s Early Atmosphere, 2-12-1992, Science, Vol. 259, Issue 5097, pp. 920-926.  DOI: 10.1126/science.11536547.
  3. Robert M. Hazen, The Story of Earth: The First 4.5 billion Years, from Stardust to Living Planet, 2013, Penguin Books, p. 128, paraphrased.
  4. See the Wikipedia article on Unicellular Organism. See also, Andrew Pohorille, and David Deamer, “Self-assembly and Function of Primitive Cell Membranes,” Research in Microbiology 6-23-2009. 160 (7): 449–456. doi:10.1016/j.resmic.2009.06.004. PMID 19580865.
  5. I. Wagner and H. Musso, “New Naturally Occurring Amino Acids,” November, 1983, Angewandte Chemie International Edition in English. 22 (11): 816–828. doi:10.1002/anie.198308161.
  6. M.C. Latham, “Chapter 8. Body composition, the functions of food, metabolism and energy,” 1997, Chapter 8: Human nutrition in the developing world. Food and Nutrition Series, 1997, No. 29.
  7. K. Saladin, Anatomy & Physiology: The Unity of Form and Function (6th ed.), 2011,. McGraw-Hill. p. 67. ISBN 9780073378251. See also: “Proteins,” IUPAC Compendium of Chemical Terminology, 2nd ed. (the “Gold Book”), 1997, online corrected version, 2006, doi:10.1351/goldbook.P04898. See also: “What are Peptides,” Zealand Pharma A/S. Archived from the original on 4-29-2019.
  8. J.M. Berg, J.L. Tymoczko, and L. Stryer, “Protein Structure and Function,” 2002, Biochemistry, W. H. Freeman. ISBN 978-0-7167-4684-3.  See also, D.J. Selkoe, “Folding Proteins in Fatal Ways, December, 2003, Nature. 426 (6968): 900–4, bibcode:2003 Natur.426..900S. doi:10.1038/nature02264. PMID 14685251. S2CID 6451881. See also B. Alberts, D. Bray, K. Hopkin, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter, “Protein Structure and Function,” Essential Cell Biology (Third ed.), 2010, Garland Science. pp. 120–70. ISBN 978-0-8153-4454-4.
  9. Prion Diseases, https://www.hopkinsmedicine.org/health/conditions-and-diseases/prion-diseases. See also,

    See also, “Prion: Infectious Particle,” Encyclopedia Britannica. Retrieved 15 May 2018. 9 https://www.britannica.com/science/prion-infectious-agent.

  10. C.M. Dobson, “The Structural Basis of Protein Folding and its Links with Human Disease,” Feb. 2001, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences. 356 (1406): pp. 133–45. doi:10.1098/rstb.2000.0758. PMC 1088418. PMID 11260793. See also, Todd E. Golde, David R. Borchelt, Benoit I Giasson, and Jada Lewis, “Thinking Laterally About Neurodegenerative Proteinopathies,” 5-01-2013, Journal of Clinical Investigation. 123 (5): pp. 1847–1855. doi:10.1172/JCI66029. ISSN 0021-9738. PMC 3635732. PMID 23635781.
  11. First Life on Earth Archived 2012-06-29 at Archive.today windmillministries.org, Retrieved on 2008-01-18.  See also: Letters of Charles Darwin, written in 1871, published in Darwin, Francis, ed., 1887, The Life and Letters of Charles Darwin, Including an Autobiographical Chapter, Volume 3, London: John Murray.
  12. Arvin Ash, “Abiogenesis,” Ibid.
  13. Stanley L. Miller and Harold C. Urey, “Organic Compound Synthesis on the Primitive Earth.” 1959, Science. 130 (3370): 245–51. Bibcode:1959Sci…130..245M. doi:10.1126/science.130.3370.245. PMID 13668555. See also, Lazcano and J.L. Bada, “The 1953 Stanley L. Miller Experiment: Fifty Years of Prebiotic Organic Chemistry,” 2004, Origins of Life and Evolution of Biospheres.” 33 (3): 235–242. Bibcode:2003OLEB…33..235L. doi:10.1023/A:1024807125069. PMID 14515862. S2CID 19515024.
  14.  Oró J, Kimball AP (August 1961). “Synthesis of purines under possible primitive earth conditions. I. Adenine from hydrogen cyanide”. Archives of Biochemistry and Biophysics. 94 (2): 217–27. doi:10.1016/0003-9861(61)90033-9. PMID 13731263. See also,  Oró J, Kamat SS (April 1961). “Amino-acid synthesis from hydrogen cyanide under possible primitive earth conditions”. Nature. 190 (4774): 442–3. Bibcode:1961Natur.190..442O. doi:10.1038/190442a0. PMID 13731262. S2CID 4219284. See also, Oró J (1967). Fox SW (ed.). Origins of Pre-biological Systems and of Their Molecular Matrices. New York Academic Press. p. 137.
  15. Johnson AP, Cleaves HJ, Dworkin JP, Glavin DP, Lazcano A, Bada JL (October 2008). “The Miller volcanic spark discharge experiment”. Science. 322 (5900): 404.  Bibcode:2008Sci…322..404J. doi:10.1126/science.1161527. PMID 18927386. S2CID 10134423. See also, “Lost’ Miller–Urey Experiment Created More Of Life’s Building Blocks”. Science Daily. October 17, 2008. Archived from the original on October 19, 2008. Retrieved 2008-10-18.
  16. Laura Mallonee, “Turns Out Crystallized DNA Is Crazy Pretty,” 2015, WIRED Magazine, https://www.wired.com/2015/08/linden-gledhill-crystalized-dna/.
  17. L.A. Moran LA (2011-03-24). “The Total Size of the human genome is very likely to be ~3,200 Mb,” 3-24-11, Sandwalk.blogspot.com. Retrieved 2012-07-16.

    See also, “The Finished length of the human genome is 2.86 Gb,” Strategicgenomics.com, 6-12-2006-06,  Retrieved 2012-07-16. See also, International Human Genome Sequencing Consortium (October 2004). “Finishing the euchromatic sequence of the human genome,” October 2004, Nature. 431 (7011): 931–45. Bibcode:2004Natur.431..931H. doi:10.1038/nature03001. PMID 15496913.

  18. Celia Henry Arnaud, “How the First Nucleotides Might Have Formed on Earth,” Chemical & Engineering News, 4-27-2016.
  19. Celia Henry Arnaud, “How the first nucleotides might have formed on Earth,” Chemical and Engineering News, 4-27-16, referencing the publication: “Spontaneous Formation and Base Pairing of Plausible Prebiotic Nucleotides in Water,” by Brian J. Cafferty, David M. Fialho, Jaheda Khanam, Ramanarayanan Krishnamurthy & Nicholas V. Hud, Nature Communications, volume 7, Article number: 11328 (2016).  DOI: 10.1038/ncomms11328).
  20. their results were published in the 2017 Proceedings of the National Academy of Sciences PNAS 2017; 4-10-2017, DOI: 10.1073/pnas.1700010114.
  21. S. Konikkat,“Dynamic Remodeling Events Drive the Removal of the ITS2 Spacer Sequence During Assembly of 60S Ribosomal Subunits,” February 2016, in S. cerevisiae (Ph.D. thesis), Carnegie Mellon University. See also, E.W.  Weiler and L. Nover, (2008). Allgemeine und Molekulare Botanik, in German, Stuttgart: Georg Thieme Verlag. p. 532. ISBN 978-3-13-152791-2. See also J. de la Cruz J, K. Karbstein, and J.L. Woolford, (2015). “Functions of ribosomal proteins in assembly of eukaryotic ribosomes in vivo”. Annual Review of Biochemistry. 84: 93–129. doi:10.1146/annurev-biochem-060614-033917. PMC 4772166. PMID 25706898.
  22. https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(06)00020-1.
  23. http://sitn.hms.harvard.edu/flash/2011/issue88/.
  24. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html.
  25. Alexis Madrigal, “Self-Replicating Chemicals Evolve Into Lifelike Ecosystem,” Wired, 1/8, 1889.  https://www.wired.com/2009/01/replicatingrna/.
  26. https://www.chemistryworld.com/news/self-replicating-molecules-show-signs-of-metabolism-for-the-first-time/4012152.article.
  27. https://www.khanacademy.org/science/ap-biology/cellular-energetics/cellular-respiration-ap/a/fermentation-and-anaerobic-respiration.
  28. https://forces.si.edu/atmosphere/02_02_01.html#:~:text=When%20Earth%20formed%204.6%20billion,carbon%20dioxide%20as%20today’s%20atmosphere.
  29. https://en.wikipedia.org/wiki/Miller%E2%80%93Urey_experiment#:~:text=The%20Miller%E2%80%93Urey%20experiment%20(or,of%20life%20under%20those%20conditions.
  30. https://simple.wikipedia.org/wiki/Anaerobic_respiration.
  31. https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/16%3A_Microbial_Ecology/16.4%3A_Nutrient_Cycles/16.4F%3A_The_Sulfur_Cycle
  32. Madigan MT, Martinko JM, Bender KS, Buckley DH, Stahl DA (2014). Brock Biology of Microorganisms. Benjamin-Cummings Pub Co. pp. 448–449. ISBN 978-0321897398. See also, R. Rabus, TA Hansen, and F Widdel,   “Dissimilatory Sulfate-and Sulfur-Reducing Prokaryotes,” 2006, The Prokaryotes, 2006, Springer Publishing, pp. 659–768. doi:10.1007/0-387-30742-7_22. ISBN 978-0-387-25492-0.
  33. https://en.wikipedia.org/wiki/Sulfate-reducing_microorganisms, 34 LL Barton and GD Fauque, “Biochemistry, Physiology and Biotechnology of Sulfate-Reducing Bacteria,” Advances in Applied Microbiology, 2009, pp. 41–98. doi:10.1016/s0065-2164(09)01202-7. ISBN 9780123748034. PMID 19426853.
  34. https://en.wikipedia.org/wiki/Sulfur-reducing_bacteria#:~:text=Acidithiobacillus%20are%20chemolithoautrophics%2C%20Gram%2Dnegative,and%20nitrogen%20from%20the%20atmosphere.
  35. https://www.google.com/url?sa=i&url=http%3A%2F%2Fwiki.biomine.skelleftea.se%2Fwiki%2Findex.php%2FSulfate_reducing_bacteria&psig=AOvVaw0lzzAafSRHXcc93VaXn8L-&ust=1613421722267000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCKjI5bae6u4CFQAAAAAdAAAAABAD, footnotes 2, 12, 13, and 14.
  36. https://en.wikipedia.org/wiki/Anaerobic_organism#:~:text=An%20anaerobic%20organism%20or%20anaerobe,that%20requires%20an%20oxygenated%20environment.

  37. Robert Hazen, Ibid., p. 135.
  38. https://www.umassmed.edu/rti/biology/role-of-rna-in-biology/.
  39. Christopher Packham, “Researchers Produce all RNA Nucleobases in Simulated Primordial Earth,” 4-21-2017, Phys.org News, https://phys.org/news/2017-04-rna-nucleobases-simulated-primordial-earth.html. See also, Walter Gilbert, “The RNA World,” February 1986, Nature 319 (6055): 618. Bibcode:1986Natur.319..618G. doi:10.1038/319618a0. S2CID 8026658.
  40. Khan Academy, RNA World AP.BIO: SYI‑3 (EU), SYI‑3.E (LO), SYI‑3.E.2 (EK)
  41. BH Patel, C Percivalle, DJ Ritson, CD Duffy, and JD Sutherland, “Common Origins of RNA, Protein and Lipid Precursors in a Cyanosulfidic Protometabolism,”April 2015, Nature Chemistry. 7 (4): 301–7. Bibcode:2015NatCh…7..301P. doi:10.1038/nchem.2202. PMC 4568310. PMID 25803468.
  42. Nicholas Wade, Nicholas (May 4, 2015). “Making Sense of the Chemistry That Led to Life on Earth,” 5-4-2015, The New York Times.  See also, SD Copley, E Smith, and HJ Morowitz, “The Origin of the RNA World: Co-evolution of Genes and Metabolism,” Bioorganic Chemistry. 35 (6): 430–43.
  43. M. Root-Bernstein M and R. Root-Bernstein, “The Ribosome as a Missing Link in the Evolution of Life,” February 2015, Journal of Theoretical Biology. 367: 130–158. doi:10.1016/j.jtbi.2014.11.025. PMID 25500179.
  44. “The RNA Origin of Life,” NOVA Labs, https://www.pbs.org/video/nova-labs-rna-origin-life/. See also, Kahn Academy, “The RNA Origin of Life, https://www.khanacademy.org/science/ap-biology/natural-selection/origins-of-life-on-earth/v/originoflife.
  45. Liang Shen and Ji Hong-Fang, “Small Cofactors May Assist Protein Emergence from RNA World: Clues from RNA-Protein Complexes,” 2011, PLOS ONE. 6 (7): e22494. Bibcode:2011PLoSO…622494S. doi:10.1371/journal.pone.0022494. PMC 3138788. PMID 21789260.
  46. R.J. Mackenzie, “DNA vs. RNA – 5 Key Differences and Comparison,” 12-18-2020, Genomics Research from Technology Networks.
  47. “Genome Variations: How Different is One Human Genome from Another?,” Jan 15, 2003, www.genomenewsnetwork.org.,resources, Ch. 4_1.
  48. Robert Hazen, Ibid. pp. 129-30.
  49. Kendall Powell, “How Biologists are creating life-like cells from scratch: Built from the bottom up, synthetic cells and other creations are starting to come together and could soon test the boundaries of life,” Nature, News Feature 11-7-2018.”
  50. Kendall Powell, How biologists are creating life-like cells from scratch, Nature Magazine, Nature 563, 172-175 (2018) https://www.nature.com/articles/d41586-018-07289-x