And the LORD God formed man of the dust of the ground, and breathed into his nostrils the breath of life; and man became a living soul. And the LORD God planted a garden eastward in Eden...

Genesis 2:7-8

But if (and oh! what a big if!) we could conceive in some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity, etc., present, that a protein compound was chemically formed ready to undergo still more complex changes...

Charles Darwin, Letter of 1871

PART I: Approaching The Problem

It took a long time for Europeans to start to think about the origin of life in naturalistic terms. Before the development of modern biochemistry, it wasn't even possible to define what life was, let alone account for its origin. Moreover, the intellectual strangulation resulting from the triumph of Christianity in the Western World lingered long after the period known as "The Enlightenment," which flowered in the eighteenth century. The magical thinking which permeated Christian societies made it all but impossible for even great scientists to contemplate the origin of life in purely materialistic terms.

It is one of the great ironies in the history of science that it was a major advance in scientific understanding which caused a crippling setback in research concerning the origin of life. In the 1860s when the colossus of French science, Louis Pasteur, disproved the hypothesis of spontaneous generation - the idea that life can come from non-life (e.g., maggots from rotting meat, or bacteria from beef-broth) - he effectively ruled out the notion that it could be scientifically respectable to maintain that life had originated spontaneously in the remote past. Pasteur, despite his magnificent discoveries in what today would be called enzymology, remained a Roman Catholic throughout his life. In fact, Pasteur is reported to have died with a crucifix in one hand and the hand of his wife in the other. Despite his pioneering studies of the purely chemical underpinnings of living cells, he seems never completely to have given up the Vitalistic beliefs that sprang so easily from the religious milieu in which he lived - although it is now known that he privately allowed for the possibility that life might arise spontaneously as the result of an "asymmetric force" acting on organic and inorganic materials.

The Vitalists, it will be remembered, believed that living things could not be explained completely in terms of matter and ordinary energy. Translating into a more modern jargon the mythological view inherent in the passage from Genesis quoted above, the Vitalists maintained that living beings differed from non-living or dead beings by virtue of their possession of an élan vital - a "vital force." What should have been the death-blow to this idea had actually been delivered back in 1828 by the German Chemist Friedrich Wöhler when he synthesized the organic compound urea from ammonium cyanate, an inorganic substance. (Organic compounds were so named because they were found only in organisms.) When Wöhler demonstrated that living kidneys were not needed to produce this humble substance, he dispelled much of the mystique that had enveloped the chemistry of life. By the time of Pasteur's elegant experiments disproving the idea of spontaneous generation, (see Figure 1), numerous "organic" compounds had been synthesized in laboratories. A mechanistic view of life had been steadily advancing, but Pasteur's authority stopped it cold. It would not be until the 20s of the present century before a completely mechanistic, materialistic view of living systems could resurface and turn its attention to the problem of how life had arisen on the primordial earth.

Figure 1. Pasteur's swan-necked flask experiment. Broth has placed in the flask and sterilized by boiling. The neck of the flask was drawn out into a narrow "swan's neck," which would admit air to the broth chamber but would serve as a trap for bacteria suspended in the air. To prevent bacteria being sucked into the flask during the rush of air into the flask as the boiled broth cooled, the inrushing air was sterilized by being made to pass through a red-hot platinum pipe temporarily connected to the mouth of the flask. As long as the neck of the flask remained unbroken, the broth remained clear and free of bacteria. If the neck of the flask were broken off, however, or if broth were sloshed into the neck of the flask and then allowed to run back into the chamber, the broth became cloudy and full of bacteria. This proved that the bacteria had come from the air and had not been generated spontaneously by the broth itself.

It is not surprising that the first substantial efforts to account naturally for the origin of life came from the Soviet Union, where completely Atheistic views were free to flourish, and from England - where the steadily growing Darwinian tradition had rendered the Anglican Church as impotent as the Monarchy. The Russian theorist was a man by the name of Alexandr I. Oparin; the British scientist was the multifaceted Atheist thinker J. B. S. Haldane.

It was in 1924 that Oparin systematically first set forth his ideas on how life could have originated, with the publication of a small book titled The Origin of Life.¹ This was then greatly expanded into a major treatise, The Origin of Life On The Earth,² which underwent progressive revisions throughout the author's life (the third edition was published in 1957). Haldane's first publication on the subject (in which he introduced the idea of a "hot, dilute soup," now referred to as "primordial soup"), so far as I can determine, appeared in 1928, in an essay published in the Rationalist Annual.³ Once the taboo against scientific investigation of the origin of life had been broken, scientists all over the world jumped into the fray, and the last fifty years have witnessed an explosive growth of information and ideas relative to the problem of biopoiesis (the formation of living systems). Today, the International Society for the Study of the Origin of Life publishes a fine journal, Origins of Life and Evolution of the Biosphere, which is devoted entirely to the subject of biopoiesis. While we must admit that we do not yet have a comprehensive theory explaining biopoiesis with the degree of reliability and comprehensiveness, say, as the origin of species - or even the origin of stars and planetary systems - we are closing in on such a theory at an excitingly rapid rate. Not a week goes by which lacks some new report of findings relevant to the problem of biopoiesis.

It was, however, Charles Darwin himself who resolved the dilemma posed by Pasteur's experiments. In a letter quoted in part at the beginning of this article, he explained why Pasteur's demonstration that life does not arise spontaneously today is not adequate proof of the notion that life could not have originated spontaneously in the early days of the earth.

It is often said that all the conditions for the first production of a living organism are present, which could ever have been present. But if (and oh! what a big if!) we could conceive in some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity, etc., present, that a protein compound was chemically formed ready to undergo still more complex changes, at the present day such matter would be instantly devoured or absorbed, which would not have been the case before living creatures were formed.⁴

In short, it is the presence of life already developed which rules out the emergence of new life from the earth. Darwin could also have noted that the confines of Pasteur's swan-necked flasks were too small to allow for the trillions of different chemical interactions which must have been required, and that Pasteur's life was too short to pass judgment on processes which must have required millions of years to come to completion. Scientists attempting to make theoretical models of processes extending over large volumes of space and vast stretches of time have to find ways to scale down both time and space. It is only in recent times that we have begun to learn how to design experiments in which we scale down for time as well as space.

Although Oparin devoted considerable attention to the problem Pasteur posed for studies of the origin of life, Haldane was altogether unawed by the French authority. In his 1928 essay, "The Origin of Life," he disposed of Pasteur's experiments in one paragraph:

It is hard to believe that any lapse of time will dim the glory of Pasteur's positive achievements. He published singularly few experimental results. It has even been suggested by a cynic that his entire work would not gain a Doctorate of Philosophy today! But every experiment was final. I have never heard of anyone who has repeated any experiment of Pasteur's with a result different from that of the master. Yet his deductions from these experiments were sometimes too sweeping. It is perhaps not quite irrelevant that he worked in his latter years with half a brain. His right cerebral hemisphere had been extensively wrecked by the bursting of an artery when he was only forty-five years old; and the united brain-power of the microbiologists who succeeded him has barely compensated for that accident. Even during his lifetime some of the conclusions which he had drawn from his experimental work were disproved. He had said that alcoholic fermentation was impossible without life. Buchner obtained it with a cell-free and dead extract of yeast. And since his death the gap between life and matter has been greatly narrowed.⁵

Before we examine the writings of Oparin, Haldane, or subsequent students who have pondered the problem of biopoiesis, it is necessary first to consider just what it is that we seek to explain. Just what is life, anyway?

Ignoring, for the moment, the question of whether viruses should be considered living, we may note that all forms universally agreed to be alive share certain basic features. For example, they are cellular in structure and are comprised of at least one cell - a jelly-like object bounded by a structurally dynamic membrane composed of lipids (fatty substances) and proteins. All living things are able to reproduce - at least at the cellular level. (Worker ants and Roman Catholic nuns, although alive, tend not to reproduce very often at the organismal level!) All living things are capable of evolutionary change, i.e., producing offspring that differ from them to a certain degree. Living things interact with their environment, (eliminating wastes and taking in raw materials needed to produce energy), replace worn-out parts, and grow. The energy produced may be mechanical (used for movement) or chemical (used to synthesize the components of the cell). Light energy also may be absorbed and used by some cells, and certain types of cells may actually produce light - although light production is not considered a fundamental process of living systems in general.

In addition to the features listed - features which can be found listed in every high school biology textbook published since 1920 - we may note that all modern forms of life can be thought of as information-containing systems in which information (specifically, instructions on how to build a living organism according to certain specifications) is stored in the form of giant, self-replicating molecules (the genes), which are maintained by a regular cycle of chemical changes involving subordinate types of molecules. The chemical cycle we call life is diagrammed in Figure 2. Readers will note that the keystone molecule in the chemical cycle of life is DNA (deoxyribonucleic acid) - the stuff that genes are made of. Given the proper raw material (medium-sized molecules known as deoxyribonucleotides), DNA molecules are able to reproduce themselves. To produce the raw materials, however, requires a number of chemical reactions.

Figure 2. The chemical cycles defining life today. The arrows should be read "causes to form or occur," rather than "turns into," as would be the case with ordinary chemical equations. Thus, given a supply of deoxyribonucleotides, DNA is able to reproduce itself; given ribonucleotides, it can cause RNA to be formed. RNA in turn can cause proteins to be formed. Enzyme proteins then can control nearly all the chemical reactions needed to keep the cell going, including the production of amino acids, ribonucleotides, and deoxyribonucleotides, the raw materials for making proteins, RNA and DNA, respectively. All the chemistry taking place in the cell can be viewed as merely a means of providing for the replication of DNA. Just as a chicken can be thought of an egg's way of making another egg, cells and bodies can be thought of as DNA's way of making more DNA!

As can be inferred from Figure 2, just about every chemical reaction occurring in the cell is regulated by enzymes - workhorse proteins which are able to speed up chemical reactions and cause them to be carried out with high precision. Enzymes, however, like all proteins, require the help of RNA (ribonucleic acid) to be formed. RNA, in turn, is dependent upon information stored in DNA in order to be formed.

How did this cycle of interlocking chemical reactions begin? That is the fundamental problem we have to solve.

In Search of The Primitive

It is fairly certain that the first living things were neither elephants nor orchids - still less were they human beings, as claimed in Genesis 2:7! In accounting for the appearance of the first living things, therefore, we shall ignore such complex, highly-evolved forms. Quite obviously, the first living things were extremely primitive and simple things - simpler than anything alive today. In seeking clues to the nature of the first living things, clearly, we are better off studying the simplest forms of life available, rather than worrying about complex organisms such as poppies or penguins. If we can account for the origin of the simplest known organisms, the rest of the living world can be explained by known principles of evolutionary transformation.

In searching for the most primitive forms of life, we have to go way down - lower than televangelists, even. This constraint rapidly narrows the field to just two candidates: viruses and bacteria.

Although viruses are structurally simpler than bacteria, it no longer appears that they are more primitive than bacteria. Moreover, there is dispute over their being completely "alive." Viruses lack a cellular structure and typically are composed of just two components: a core molecule of DNA or RNA, and a shell or envelope composed of a small variety of protein molecules. Many viruses are so simple that they were synthesized in the laboratory years ago. All known viruses are parasites: although they carry genetic information on how to reproduce themselves, in fact they do so only inside the cells of other organisms, and it is really the host organisms that provide the machinery to reproduce the viruses! No free-living viruses are known. Unlike all indisputably living things known, viruses can be crystallized like salt or sugar, stored indefinitely, redissolved, and found to be fully capable of infecting host cells - as if their "life-cycles" had never been interrupted!

Rather than being connecting links between the nonliving and living worlds, as once supposed, it now appears that viruses are actually the product of a long evolution and represent the ne plus ultra of parasitic reduction. Whereas parasitic animals such as tapeworms have lost eyes, digestive tracts, and other anatomical features that their free-living ancestors once possessed, viruses seem to have lost all but the absolute essentials in becoming the world's most perfect parasites. Having lost even a cellular structure, viruses are essentially "naked genes" - clothed only in a few proteins, which are needed to assist entry into host cells and subversion of their metabolic machinery.

If viruses are not the most primitive forms of life today, then we must search among the bacteria and their kin - the so-called prokaryotes. Unlike the eukaryotes (organisms which have cells containing nuclei and other complex organelles such as chloroplasts and mitochondria), the prokaryotes are characterized by extreme austerity of construction. Their genome (their entire set of genes) - instead of being organized into chromosomes and surrounded by a nuclear membrane - typically consists of a long, circular strand of DNA which is anchored to the cell membrane and dangles into the cytoplasm of the cell. In keeping with their overall simplicity, prokaryotic cells tend to be smaller than eukaryotic cells: when there's less to be packaged, the package is smaller.

Of all the prokaryotes known today, the smallest and least complicated are the mycoplasmas, the so-called pleuropneumonia-like organisms (PPLO). Ironically, these organisms were discovered by Louis Pasteur, but he was unable to isolate them or see them, electron microscopes in those days being as hard to find as the present king of France. The smallness (and the necessary simplicity) of these cellular beasties is hard to imagine without help.

In a classic article written long ago in Scientific American,⁶ Harold Morowitz and Mark Tourtellotte gave some helpful comparisons to help readers visualize just how small these organisms are. The smallest PPLO "elementary bodies: (reproductive cells) are about 0.1 micron in diameter - about one-tenth the diameter of the average bacterium. This is one-hundredth the size of mammalian tissue cells, and about one-thousandth the size of an amoeba. Thus, a PPLO cell is as close in size to an atom as it is to a 100-micron protozoan! (See Figure 3). A better measure of the simplicity of these organisms is their mass, however, since that gives one a sense of how much material is actually packed into the cell. Considered in terms of mass, an amoeba is about a billion times bigger than a PPLO, and a laboratory rat is about a billion times bigger than an amoeba!"

Figure 3. The Pleuropneumonia-like organism (PPLO) elementary body (reproductive cell) compared in size to the smallest cell theoretically possible and to the atomic and molecular components of which it is composed.

There are theoretical limits to how small a self-reproducing entity can be, and a lower limit to the number of "worker molecules" it can contain. The PPLO elementary body comes very close to this theoretically smallest-possible cell, being only about twice its diameter and eight times its mass. In terms of molecular content, the PPLO elementary body is simple enough that synthesis in the laboratory is not at all out of the range of possibility in the near future.

Some numbers: The hypothetically smallest cell possible would have to contain at least 1.5 million atoms (not counting the atoms of water molecules). The PPLO elementary body contains twelve million atoms. The DNA molecule which encodes the PPLO genome has a molecular weight of 2.88 million daltons, and the smallest theoretically adequate molecule would weigh about 360,000 daltons (a dalton is approximately the weight of a hydrogen atom). In terms of the number of amino acid and nucleotide units required (the building blocks of proteins and DNA/RNA, respectively), the PPLO gets by with only 600,000, as compared with the minimum possible of 75,000 (by contrast the "adult" PPLO contains nearly 9.4 million such building blocks and bacteria contain vastly greater numbers). The most exciting statistic, however, is the small number of macromolecules (proteins, DNA, or RNA) needed to keep a PPLO elementary body running: about twelve hundred. This is so small a number that one would have to be skeptical to the point of pathology to suggest that creation of such an organism in the laboratory will be forever impossible.

Of course, the creation of PPLO in the laboratory would not be proof that life has ever originated without intelligent guidance. It will be our task in Part II (Stardust in the Primordial Soup") and Part III ("The First Cells") of this article to show that it is possible to simulate the conditions of the primitive earth, and to explain first how the chemicals of life could have originated without intelligence, and then how the dynamic organization of living systems could have begun. We end Part I with the assurance that the simplest forms of life known today are very simple indeed, and they are a realistic target at which to aim in trying to account for the origin of life on planet earth. They possess no frills to sidetrack us in our quest, and allow us to reconstruct more easily the intermediate stages which must have been involved in the transition from the prebiotic would to the world of life. In Parts II and III we shall see that life is a natural product of cosmic chemistry, and that there is no need to invoke supernatural powers - breathing or otherwise - to imbue earth's productions with the pulse of life.

PART II: Stardust in the Primordial Soup

Stardust isn't just for making songs: it is the very stuff of which life is made. Life is a phoenix, born of cosmic cinders cast into space by the death-throes of stars no longer sparkling in the throng above our heads. Our sun was not among the first generation of stars formed when the Big Bang made possible the condensation of energy into matter, and the aggregation of matter into nebulae and stars. Theorists tell us that the first stars were composed mostly of hydrogen, and that although there may have been a fair amount of primordial helium, with traces of lithium and beryllium, the material emanating from the explosion that generated the universe contained no carbon, no nitrogen, no oxygen, nor any other of the heavier elements that make up our bodies, our planet, or our star the sun. Some of those elements, particularly the lighter ones, were generated by the fusion of primeval hydrogen in the fiery bowels of first-generation stars. Most of the heavier elements, however, appear to have been formed not during the lives of those stars, but rather during their explosive deaths, when they turned into novae or supernovae.

It is now apparent that our day-star, the sun, like the life that it has spawned, is also a phoenix. It has arisen from the ashes and crematory gases hurled into space as older stars exploded - like nuclear pressure-cookers blowing off their lids - creating vast funerary clouds, or nebulae, of dust and gas in the interstellar regions of our galaxy. From the recondensation of such a nebula, perhaps triggered into collapse by a shock-wave emanating from a near-by nova or supernova, was born our sun, with its attendant retinue of planets, satellites, and comets.

The world was a very different place before it gave birth to the biosphere. With no vegetation covering the surface of the protocontinental crust, the force of erosion was far more formidable than now. Today, the flow of meteoric waters is softened, slowed, and tamed by a green velvet cloak of vegetation, which shields the planetary surface from aerial violence and attack. A layer of ozone, high in the stratosphere, shields the vegetation from the withering rays of ultraviolet light streaming down upon it from the sun. But it was not always so.

Before the advent of algae and their descendants, the green plants, there was very little free oxygen in the atmosphere. This is because it is their advanced type of photosynthesis that generates almost all the oxygen of the atmosphere. Before there were algae and plants, there was no photosynthesis capable of producing oxygen as a by-product,⁷ and the only free oxygen that could have found its way into the earth's atmosphere would have been the small amount resulting from the radiation-induced break-down of water molecules in the upper atmosphere.

Oxygen is a highly reactive substance, and it does not stay long in the atmosphere. It is continuously reacting, burning organic material to produce carbon dioxide, and rusting iron and other mineral elements in the earth's crust to produce redbeds and similar memorials to photosynthetic organisms of the past. If all life suddenly were to go extinct, within approximately two thousand years there would be only trace amounts of oxygen left in the atmosphere! It is quite obvious, therefore, that before life existed the atmosphere was essentially devoid of oxygen.

The fact that the primitive atmosphere lacked oxygen was of great good fortune during the period in which life came into being, for oxygen is a fierce enemy of all the types of molecules needed for life. With oxygen present in the atmosphere, sugars, amino acids, and all the other carbon-containing compounds needed to make living cells either would have been broken down by oxygen soon after their formation, or - most probably - would not have formed in the first place. One of the major reasons life does not originate spontaneously today is that the presence of oxygen makes it impossible. (Another reason, known already to Charles Darwin over a century ago, is that any organic molecules being formed spontaneously today would be devoured by already living organisms - long before those molecules could achieve the complex organization needed for self-replication.) Still yet today, we find reminders of an earth before oxygen in the many species of anaerobic microorganisms that fester in our wounds and poison our improperly preserved vegetables. Thriving in the absence of oxygen, these primitive organisms are snuffed out by the same gas that feeds the fires of higher forms of life.

Although we can be quite certain the earth's atmosphere lacked oxygen (and the protective shield of ozone derived therefrom) at the time life evolved, there is considerable uncertainty as to just what its composition was. It seems clear that the composition of the atmosphere changed during the first half-billion years of its existence - the period during which life originated. Arguing by analogy with the atmospheres of the giant planets, such as Jupiter and Saturn, early students of biopoiesis (the origin of life) assumed that the early atmosphere was highly 'reduced,'⁸ containing substances such as hydrogen (H₂), water vapor (H₂O), methane (CH₄), ammonia (NH₃), hydrogen sulfide (H₂S), etc. Many of the earliest experiments attempting to learn what kinds of molecules could form spontaneously (which we shall examine presently) employed this type of atmosphere.

Persistent efforts to locate ancient sedimentary rocks bearing evidence of having been exposed to such an atmosphere have, however, been quite disappointing, and most students today feel that the early atmosphere - generated by volcanic out-gassing during the separation and consolidation of the earth's core - contained mostly hydrogen, water vapor, nitrogen (N₂), carbon monoxide (CO), and hydrogen sulfide, with minor amounts of methane, carbon dioxide (CO₂), and sulfur dioxide (SO₂). There is reason to suppose that this gradually changed into an atmosphere composed mostly of water vapor, carbon dioxide, nitrogen, and sulfur dioxide, with small amounts of carbon monoxide, methane, hydrogen sulfide, and hydrogen.

I am not at all surprised that we have not yet found any rocks from the earliest period of the earth's history. We now know that the earth's crust is continuously being recycled by the forces causing continental drift; the older a hunk of real estate might be, the greater is the probability that it has been recycled during the four and one-half billion years that our planet has been in business. Moreover, there is reason to believe that a primordial reducing atmosphere of the kind assumed by early investigators would not have existed very long. Quite rapidly, I believe, it would have been depleted of such components as methane, ammonia, etc., by their conversion into the biochemicals from which the first living things were developing. It might have taken only a few million years for such an atmosphere to be replaced by the less reducing atmosphere now accepted by most scholars. It is quite possible that the evolution of living systems was already well underway by the time sedimentary rocks had been formed in any significant quantity!

Despite the uncertainties surrounding the nature of the earth's primitive atmosphere, scientists seeking to explain the origins of the chemicals needed to form living cells are faced by more adequate possible solutions than they can handle at the moment. For example, it has been demonstrated, in experiments simulating presumed early-earth environments,⁹ that amino acids (the building blocks of proteins) and other important biochemicals can be formed in both a highly reduced environment resembling Jupiter's atmosphere and in the less reduced atmosphere now assumed by most scholars. In fact, almost any plausible atmosphere (i.e., an atmosphere free of O₂) can be used to generate a broad suite of critically important biochemicals.

These facts are very encouraging to persons who seek non-magical answers to the question "How did life begin?" - but they are frustrating to scientists who seek precise answers to all questions. Our frustration increases, moreover, when we realize that the early atmosphere may not have been the major site of biochemical production: spectroscopic astronomy shows that the simpler types of biologically important molecules are to be found throughout our galaxy, and analysis of meteorites (such as the carbonaceous chondrites) shows that most of the major biomolecules were present in the solar nebula even before it condensed to form our planet - with or without an atmosphere!

We have already noted that we have more adequate sources than we need for the production of the chemicals we need. However, we also have more adequate methods of production than we need. For example, in 1953 Stanley Miller (then a doctoral student of Nobelist Harold Urey at the University of Chicago) performed a now-classic experiment in which he simulated lightning in the early atmosphere by passing electric sparks through a glass chamber filled with a mixture of gasses resembling the Jovian atmosphere (see Figure 4). To the delight of everyone but creationists, Miller analyzed the "soup" resulting after the experiment had run for several days and discovered amino acids and other molecules of biological importance. Since then, simple variations of Miller's experiment have yielded nearly all the chemical building blocks needed to form living cells.

Figure 4. Diagram of the apparatus used by Stanley Miller to simulate lightning discharges in the primeval atmosphere. By condensing water vapor into liquid water and then reheating the water in the boiling flask, gasses were forced to circulate clockwise and pass repeatedly between the spark-discharge electrodes. Most of the more complicated reaction products formed by the action of the spark upon the components of the atmosphere were trapped in the liquid phase of the system (where they could be sampled periodically during the course of the experiment) and prevented from being degraded by repassage through the spark chamber. Creationists claim that it is cheating to put the trap into the system to prevent loss of the products attained. Actually, the water trap accurately models the role of the aboriginal ocean, into which newly-formed molecules settled, protected from further degradation by lightning. Creationists also decry variants of this experiment in which ultraviolet radiation is substituted for sparks. The radiation, they claim, would decompose biochemicals after they were formed, and thus no significant quantity of molecules could accumulate to form living systems. Non-creationists, however, are aware of the fact that the earth rotates on its axis once per day, and that ultraviolet light could not degrade molecules during the night-time, when particles would be settling out of the atmosphere into the oceans, where they would be protected from degradation by solar radiation returning on the next day. Actually, Le Châtelier's Principle, a rule well-known to high school chemists, tells us that the oceans would serve as a trap even during the day-time for many of the molecules created by the action of ultraviolet light. Although many molecules would, in fact, be degraded soon after their formation, the presence of the sea as a sink to absorb the products of synthesis would force the overall reaction to proceed in the direction of build-up rather than break-down.

Lightning, however, was not the only energy source on the primitive earth, and it is reassuring to learn that Miller's experiment (as well as experiments with less reduced atmospheres) has been rerun using ultraviolet radiation (an extremely important source of energy on the primitive earth before the ozone screen appeared), atomic radiation (mimicking the high-energy forms of radiation abounding in the solar nebula during the formation of the earth), and heat (imitating the effects of vulcanism) as energy sources - and in all cases the same general results have been obtained! Formation of the basic biochemical necessities appears to be a natural consequence of cosmic chemistry, given minimally suitable planetary conditions.

The chemistry of the cosmos is reflected in the elemental composition of the average living cell. Despite the existence of more than one hundred different chemical elements, approximately 95% of the weight of a cell is accounted for by just four elements: oxygen (about 62%), carbon (about 20%), hydrogen (about 10%), and nitrogen (about 3%). In the universe as a whole, these four elements account for about 70% of the observed mass. The universal importance of these four elements is even greater if one ignores the chemically inert elements helium and neon, which together comprise about 28% of the mass of the universe. If we calculate cosmic abundances according to the number of atoms present, rather than according to mass, the four most important bioelements comprise over 99% of the chemically active atoms in the universe!

Besides the "Big Four," living things contain a handful of other common elements. In decreasing order of importance, we may list calcium, phosphorus, chlorine, sulfur, potassium, sodium, magnesium, iodine, and iron. In terms of cosmic abundance (ignoring the Big Four and the inert elements) the relative order of elemental abundances is magnesium, iron, aluminum,¹⁰ sodium and calcium (approximately equal in abundance), phosphorus, and potassium. The stuff of life is just the ordinary stuff of stars and nebulae.

Despite the protean morphological qualities of organisms - found in shapes appropriate for life in niches as varied as hydrothermal vents at the bottoms of oceans, the frozen aeries of the Himalayas, and the reproductive ducts of squids - at the chemical level organisms display an encouragingly simple similarity. They are comprised of molecules belonging to just four major categories - lipids (fats), carbohydrates (sugars, starch, cellulose), proteins (enzymes and structural fibers), and nucleic acids (DNA and RNA) - plus a small number of important 'miscellaneous' compounds such as pigments, coenzymes, etc.

Considering the pervasive lipophobia of our culture today, it is important to say something nice about fats and to point out that lipids are - quite literally - of vital importance. Not only do they serve as a source of energy and carbon atoms that can be used to build almost any other type of molecule, lipid molecules (especially in forms combined with phosphate) are the major constituent of cell membranes. It is no exaggeration to say that life would be impossible without membranes to prevent the dissolution of cells, regulate what enters and exits, serve as sites for carrying out many chemical reactions, and to compartmentalize cells so that many chemically conflicting processes can occur simultaneously. Imagine what it would be like to try to bake a cake and a pie simultaneously if both had to be prepared together in the same mixing bowl! Because of their electrical insulating properties, lipid membranes allow cells to take on an electrical charge, making possible the evolution of brains - and the writing of this article.

Carbohydrates include simple sugars as well as polymers, such as starch and cellulose, in which thousands of single sugar molecules (glucose) are joined together to form very long, fibrous molecules. Unlike lipids, which are composed mostly of carbon and hydrogen, carbohydrates contain approximately as many oxygen atoms as carbon atoms. They are important as sources of energy, components of the cell walls of plants, and as components of the information-storing nucleic acids DNA and RNA. DNA, the stuff that genes are made of, contains the five-carbon sugar deoxyribose. RNA, which helps translate the information stored in DNA into protein structures, contains the sugar ribose. Besides sugars, nucleic acids contain phosphate and five different nitrogen-containing components referred to as nitrogenous bases (given the common names of adenine, thymine, cytosine, guanine, and uracil). Nucleic acids possess the all-important ability to reproduce themselves: they are autocatalytic.

Unlike cellulose, which is a polymer made up of thousands of identical glucose units (monomers) strung together, a nucleic acid is a polymer made up of four¹¹ different types of monomers (nucleotides) joined together. Each nucleotide is itself a complex entity, being comprised of a sugar molecule, a nitrogenous base, and a phosphate group. The ability of nucleic acids to carry genetic information derives from the non-random way in which the four types of bases are strung out along the length of the molecule. The four bases can be thought of as constituting a Morse Code-like alphabet which, although containing just four letters (A, T, C, & G), can encode the "recipes" for making everything from papal nuncios up to slime molds - and even higher. The difference between men, mosses, and mice is that their DNAs are spelled differently.

The last major category of biochemicals found in living cells contains the giant molecules known as proteins. Also known as polypeptides, proteins are polymers made up of twenty different types of monomer units, the amino acids. Amino acids are named for the fact that they contain at least two chemically active components: an amino group (-NH₂) and an organic acid group (-COOH). All amino acids contain the elements carbon, hydrogen, oxygen, and nitrogen. Several of them also contain the element sulfur. Amino acids can be joined together when the amine group of one molecule reacts with the acid group of another molecule to form a peptide linkage (the double molecule resulting is called a dipeptide). Joining hundreds or thousands of amino acids together creates a polypeptide - a protein. Proteins are extremely important as enzymes - giant molecules that serve as catalysts controlling all the multifarious chemical marriages and divorces that constitute the living condition. Protein enzymes even produce the nucleotides needed by DNA to replicate itself or produce RNA.

Among the miscellaneous compounds of biochemical importance we will mention only the pigments. Pigments are far more important than one might suppose. They do much more than color corals or paint the petals of flowers; nor does their major importance lie in the fact that they fill the photoreceptor cells of human retinas, allowing readers to see this article! Some pigments, such as the chlorophylls, allow living things to draw energy from the nuclear fires of the sun itself. Other pigments, such as the cytochromes, serve to transfer that solar energy - stored in the form of chemical bonds - from one molecular energy bank to another. Ultimately, all the energy that powers the pulse of life on earth is star light - and all of it has been captured by the chemical antennas known as pigments.

Having briefly surveyed the chemical requirements of living systems, we must now try to answer the question: How did these chemicals arise during the dawn days of our planet? How could they have come into being without the aid of supernal intelligence?

In the case of lipids, our problems are few. The presence of hydrocarbons in stellar clouds and comets, and the presence of fatty acids (hydrocarbons containing two atoms of oxygen per molecule, in addition to carbon and hydrogen) in meteorites make it likely that fatty substances were available for incorporation into protocells right from the beginning. However that may be, it is very easy to produce fatty acids and other lipids from methane-containing atmospheres exposed to electric spark or the hot surfaces of volcanic lavas. (Methane, it will be remembered, must have been at least a minor component of the early atmosphere.) Insoluble in water, lipids would have formed membrane-like oil-slicks on the surfaces of the first oceans. Given the turbulence of wave action, these oil-slicks must have frequently been broken up to form membrane-covered vesicles filled with sea water and other compounds present at the water surface. Born with the lipids - whether in the solar nebula before the aggregation of microplanets formed the earth, or in the same atmospheric processes that formed the lipids - were the most important of the pigments, especially the porphyrins, the major components of chlorophylls, cytochromes, and heme (the pigment which gives hemoglobin its red color).

The synthesis of sugars on the ancient earth was not very difficult either, although it does present a chemical puzzle for which as yet no detailed solution has been obtained. It has been known for many years that formaldehyde (H2CO) - one of the first substances formed in spark-chamber experiments - can be polymerized into simple sugars under alkaline conditions, if catalysts such as calcium hydroxide or calcium carbonate (limestone) are present. More exciting is the discovery that a common clay mineral, kaolin, if heated to the temperature of boiling water can convert dilute solutions of formaldehyde into a variety of sugars - including ribose, needed for RNA and ATP.¹²

The puzzling problem associated with carbohydrates is this: when sugars are mixed with amino acids (among the most common products of spark-chamber experiments) they put each other out of commission, interacting by the Maillard reaction to produce a brown, unappealing product resembling the stuff that forms when a slice of apple is left exposed to the air. As far as I am aware, no one has found any use for such compounds in the course of biopoiesis. A hint of a solution comes, however, from several lines of evidence. First of all, sugars do not seem to be formed as abundantly as are amino acids, and so even after a bout with the "browning reaction" there would still be amino acids left over to be converted into proteins. Secondly, except for the sugars needed in nucleotides, it does not appear that early, quasi-living protocells would have had much need for carbohydrates, and so the loss of some sugar molecules might not have had a crippling effect on biopoiesis. Thirdly, it has been discovered that the stability of sugars actually increases after they have been joined to nitrogenous bases (also easily produced in spark-chamber and other experiments). Since few experiments have been reported explaining how sugars may have joined to adenine and other bases, it is quite exciting to learn that researchers at the Laboratory of Chemical Evolution at the University of Maryland¹³ have experimental evidence showing that at least five nucleosides (nucleotides minus the phosphate group) can be formed directly by spark discharges in a methane-nitrogen-water atmosphere! Add a phosphate, and we have nucleotides ready to be polymerized into RNA or DNA. Add two more phosphates, and we have molecules like ATP. With ATP, there seems to be no limit to what can be done!

We have several times already noted that amino acids are among the most abundant products of experiments simulating primitive-earth syntheses. It is interesting to note that the most common types of amino acids resulting from Urey-Miller simulations (glycine, alanine, and glutamic and aspartic acids) just happen to be four of the five most commonly occurring amino acids found in organisms. Serine, the fifth amino acid, is produced abundantly in certain other types of experiments. Once again, the chemistry of life seems to be inherent in the chemistry of the cosmos.

At this point we may note that we have been able to account for the natural origin of most of the molecules comprising living things. We have seen that lipids, pigments, amino acids, nitrogenous bases, and sugars could have formed easily in the early atmosphere - if in fact they were not there from the very beginning as an inheritance from the solar nebula which formed the solar system. What remains to be shown in this article is how amino acids could have been polymerized into proteins (using only "left-handed" amino acids), and how nucleotides could have been polymerized into RNA and DNA.

The remaining problems are a bit trickier than those we have examined so far. Let us consider first the problem of "left-handed amino acids." All but the simplest of amino acids, glycine, contain what is called an asymmetric carbon atom. This is simply a carbon atom linked by its four possible bonds to four different types of chemical groups. As an example we may consider the second-most simple amino acid, alanine (see Figure 5). It is helpful to visualize the asymmetric carbon as floating in the center of a triangular pyramid (tetrahedron), with its four bonds stretching to chemical groups located at the four corners of the pyramid. As can be seen in Figure 2, there are two different ways in which the attached groups can be arranged, and these two arrangements are mirror images of each other. Looking at both molecular structures simultaneously, readers can see that the "left-handed" L-alanine¹⁴ appears to be a mirror reflection of the "right-handed" D-alanine. Just as there is no way to rearrange a left-handed glove to turn it into a right-handed one (short of turning it inside-out!), so too there is no way D-alanine can be rotated or inverted to turn it into L-alanine.

Figure 5. Left- and right-handed forms of the amino acid alanine. Living things produce only the left-handed variety (L-alanine), whereas artificial syntheses produce a 50/50 mixture of the two forms.

It is a curious fact that all the amino acids that go into the composition of proteins are exclusively of the L-form. No real proteins are known that contain D-amino acids, although the bacterium Bacillus brevis produces a protein-like antibiotic known as gramicidin S, which contains D-phenylalanine, as well as ornithine - which is not one of the standard set of twenty amino acids found in ordinary proteins. Why only left-handed amino acids are used is an unsolved puzzle. It is possible that early forms of life used mixtures of left- and right-handed molecules. After all, when one produces amino acids in the laboratory and in primitive-earth simulations, half of the molecules produced are left-handed, half are right-handed. But when living things produce them, all are left-handed.

There is a tendency, when mixtures of left- and right-handed amino acids polymerize into peptides, for the polymers to contain more L than D components.¹⁵ It is possible that living things have simply exaggerated a bias inherent in the chemistry of peptide formation. However that may be, the solution to our puzzle awaits in studies yet to be done.

The discussion up until now has more or less assumed that all the chemicals created in the atmosphere sooner or later ended up as components of a "primordial soup" - the oceans, seas, and ponds of the new-born world. That such a situation was indeed the fact seems to me to be established beyond reasonable doubt. But if that be true, it creates a difficulty: joining amino acids (and nucleotides) into linear polymers involves the process of dehydration - removing a molecule of water from each pair of molecules being joined together. It is not immediately obvious how water could have been removed from molecules that were dissolved in it!

One of the first to solve this problem was Professor Sidney Fox, of the University of Miami. He showed that water containing amino acids could have splashed up onto hot lava, the water would have evaporated, the amino acids would have formed a dry film, and could have been dehydrated to produce peptides. Experimentally, this has been done, and the result is a protein-like polymer Fox calls "proteinoid." Proteinoid closely resembles natural proteins, although it is less regular in its structure. Like natural proteins, proteinoids possess catalytic abilities - including autocatalytic abilities! Compared to modern enzymes, however, their capabilities are quite feeble. But we must not forget that before the advent of organisms possessed of fancy enzymes, any molecule possessing even weak enzymatic abilities would have a competitive advantage over other molecules in the primeval soup.

Volcanic temperatures are not, however, necessary to dehydrate proteins (or nucleotides, for that matter). James Lawless, a researcher at NASA's Ames Research Center in California, and his colleagues have shown that clay crystals can catalyze the polymerization of amino acids and nucleotides.¹⁶ Solutions containing the molecules to be joined together are sprayed onto clay surfaces, and the surfaces are subjected to fluctuations between hot, dry, cold, and wet conditions - such as might occur in evaporating tidal pools. Clays containing zinc were able to link nucleotides together, to produce nucleic acids. It is interesting to note that DNA polymerase, the modern enzyme that helps DNA reproduce, also contains zinc.

Clays containing copper collected and joined together a wide variety of different types of amino acids. Clays containing traces of nickel, however, adsorbed and polymerized only the twenty types of amino acids found in proteins. Why it is, that of the hundreds of different amino acids possible, proteins in everything from fish to philosophers are composed of a standard set of just twenty, has long been a puzzle. Perhaps they are a memory of a distant shore, long ago, where nickel ions trapped in the atomic cages of clay particles forged a chemical covenant among a score of humble fellow prisoners - a company of covenanters that have never deserted each other, despite the flight of eons, and have gone on to perform nearly all the tasks that life has ever mastered.

Although details remain to be determined, the origins of the chemical ingredients of life are now reasonably well understood. But life is more than just a bag of chemicals. Like the flickering flame of a candle, life is flux. Life is a dynamic pattern maintained by a continuous flow of matter and energy, by a delicate balance between dead matter coming in and dead matter going out. How the flame that is life came to be poised between death and the non-living is the subject of Part III of this article, "The First Cells."

PART III: The First Cells.

The living cell - indeed life itself - huddles poised in time between the death which awaits all mortal forms and the nonliving world of prebiotic nature from which it sprang. The membrane-bounded cell, universally the structure which has arisen as the standard-bearer of the living state on earth, is - despite the naïve views of certain nineteenth-century materialists - more than just a bag of chemicals, even though chemicals are really all that it contains. Even so, there is no "vital force" to stir its atoms into life when it is present, or to leave them dead when it departs.

The living cell is a dynamic, ever-changing system in which chemicals become ordered for a while into microscopic structures, only to dissolve again as other molecules come together to form the same types of structures over again, or to replace them in the same structure. The organelles of which cells are made are no more static than a candle flame. At any given instant, the cell exhibits a dynamic pattern of chemical marriages and divorces, of energy-producing and energy-using processes, of structures forming and structures breaking down. Life is a process, not a thing.

How did this ordered process come to be? Since the cell is a highly-ordered, nonrandom entity (avoiding, however, the dull regularity of a crystal), it can be thought of as an information-containing system.¹⁷ Information is the added ingredient that brings life to otherwise lifeless atoms.

How, we must ask, could information come about without a creative, supernatural intelligence? That is the problem science yet must answer if it is to put god into the ranks of the completely unemployed.

Scientists seeking to account for the information content of living cells are heartened by the fact that information and the appearance of intelligent design can be found in nonliving nature too, in systems no adult would seriously suppose to be evidence of intelligent design. The delicate ferns and filigrees that form upon our windows in winter are thought by children to result from the intelligent efforts of Jack Frost, but those of us over the age of ten know that the ability to form such pretty pictures is in the nature of water itself. The "information" on how to form intricate crystal structures inheres in the submolecular structure of water, in the way in which the electrons orbit about the hydrogen and oxygen atoms which constitute it. The simplest of substances contain information, along with what often appears to be a program telling how to interact with the world.

In the case of living systems, however, the amount of information and pattern-directing programming found in individual molecules is increased to a dizzying degree. Although the entire cell may be considered to be an information-containing system, the fact of the matter is that most of the information content of a cell is present in the form of giant informational molecules such as DNA (which contains the "recipe" for making an entire organism of a particular type) or enzymes (proteins which can be thought of as the molecular tools with which the recipe stored in the DNA is translated into action - the baking of the cake, as it were).

It is often argued that the laws of probability are against the idea that the major informational molecules of the cell could come into existence spontaneously. "The chances that an enzyme molecule could form from just the right amino acids, in just the right sequence," it is often claimed, "is so small that if you had ten trials per second, you wouldn't get an enzyme molecule in a trillion trillion years."

There are at least three major flaws in the assumptions underlying this argument. First of all, it presumes that when the twenty amino acids of which proteins are made react promiscuously with each other, all possible combinations are of equal probability. The fact of the matter is, there is a definite bias in the way that amino acids in mixtures combine (polymerize) to form peptides and protein-like polymers. Sidney Fox, one of the greatest experimentalists studying the problem of biopoiesis (the origin of life), reports that "the varied amino acids do not polymerize randomly; instead, they have much self-instructing ability. The sequences formed are highly specific… and the polymers produced are of sharply limited heterogeneity…"¹⁸ The net result of this bias in the way amino acids join together to form "proteinoids" (protein-like polymers which form spontaneously when mixtures of dry amino acids are heated) is that molecules capable of catalyzing biologically useful reactions (i.e., the types of reactions now catalyzed by enzymes) are more likely to form than are molecules incapable of enzymatic activities. Organic chemistry is biased in favor of life.

The second problem is that the argument fails to comprehend the role of natural selection operating at the molecular level. It is common knowledge, for example, that the probability of being dealt a perfect hand at bridge is extremely small. If, however, one may "select" all the spades obtained from the first deal of cards, return the unwanted cards to the dealer (along with the cards of the other three hands), let the dealer deal again and again, each time keeping the spades obtained and returning the unwanted cards, in no time at all a "perfect hand" will be obtained. When natural selection operates at the molecular level in protocells (cell-like structures not yet able to control their reproductive activity or guarantee hereditary transmission of information with little error), any "step in the right direction" will tend to be saved, and any step in the wrong direction will go back to the "dealer."

The Third and most serious flaw in the often awesomely mathematical arguments leveled against the possibility of a natural origin of informational molecules is the assumption that the molecules in question (e.g., the enzyme catalase) must be identical to a given, modern, highly evolved standard.

Like all enzymes, catalase is a protein, a very large molecule composed of amino acids joined together. Its major function in modern cells is to break down hydrogen peroxide into water and oxygen. This is highly important, since peroxide is very destructive to the molecular machinery of the cell. Besides its amino acid structure, catalase also contains a pigment molecule, heme, which in turn, is composed of a porphyries ring (see Figure 6) and an atom of iron.

Figure 6. The structural formula for heme, the pigment found in hemoglobin, catalase, and other enzymes. (Carbon atoms occupy all places in the structure where straight lines come together.)

We can concede immediately that the spontaneous origin of a modern catalase molecule, with its four sets of 505 amino acids linked together in a very specific order, is completely unlikely. But what is rarely noted is the fact that the first cells didn't need the entire catalase molecule (if they needed catalase at all, in an environment containing little free oxygen!). In the first cells having to deal with small amounts of peroxide, any molecule that could do the job of catalase even weakly would have conferred an advantage over cells that could not break down peroxide at all.

It so happens that even the ferrous iron ion itself (Fe⁺⁺) is able to break down peroxide. If the iron is combined with a pyrrole ring (the porphyrin¹⁹ "super-ring" shown in Figure 1 is composed of four pyrrole rings arranged along the sides of a square), its catalytic ability is increased several-fold. If the iron is combined with the porphyrin ring of heme, its catalytic properties increase a thousand-fold over that of a free iron ion. Finally, adding the protein part of the catalase molecule increases the activity ten million-fold!²⁰

It is clear that for life to originate it was not necessary for catalase or any other macromolecule now found in cells to have been present. All that was needed were molecules that could do the work of these macromolecules at least a little bit. Of course, it is reasonable to expect that the protoenzymes of protocells would bear a clear chemical resemblance to at least a part of their modern counterparts in cells, and it should be possible to show how modern enzymes developed from the simpler structures of their ancestral protoenzymes. Discoveries in this area are occurring at an accelerating pace.

So-called metabolic pathways are employed by present-day cells to synthesize needed materials, convert into chemically useful form the energy of sunlight trapped by pigments, and to break down both raw materials and waste products. These pathways involve step-by-step chemical alterations of starting materials until they become the needed products. Comparison of the metabolic pathways of primitive bacteria, plants, and animals reveals many clues as to how those pathways may have originated. It is quite clear that metabolic pathways evolved precisely in the manner of the work they perform: step-by-step. At no time in the evolution of life did an entire pathway form at once.

The Heterotroph Hypothesis

To understand how metabolic pathways developed in the course of life's evolution, it is necessary to examine the way in which the first protocells came into existence. The first detailed analysis of this problem was made by the Russian biochemist Alexandr I. Oparin in 1924.²¹ Oparin is famous for his formulation of the so-called heterotroph hypothesis. The word heterotroph comes from the Greek words heteros ('another' or 'different') and trophé ('food' or 'nourishment') and refers to the fact that the first living things were unable to synthesize their own food from carbon dioxide and water in the way that green plants ('autotrophs') do, but rather were dependent upon sources of food outside themselves. Modern animals are said to be secondary heterotrophs, since they have lost photosynthetic capability and depend upon the eating of other animals and plants as sources of energy and raw materials.

According to Oparin, protocells (which he thought would have been microscopic coacervate droplets, colloidal aggregates of molecules) would have formed from the "primordial soup" of organic compounds constituting the primitive lakes and oceans of the world. Once protocells formed which were capable of self-replication, they would have sustained themselves by consuming the remainder of the broth that spawned them. At first, the protocells would have been able to utilize rather complex compounds,²² perhaps compounds that could be integrated into protocell structure without any further alteration. As time went by, however, the complex "food" molecules would have been used up, leaving molecules of lesser complexity which could be used only after some degree of chemical modification.

Although some authors have imagined this stage of chemical evolution to have constituted a "crisis" in the development of life, and have even supposed it to have been a lucky accident that any protocells developed the ability to use somewhat simpler food molecules "just in the nick of time, before they starved to death for want of the more complex molecules," the realities of chemistry make the situation less hair-raising. We must remember that at the point where the soup had been depleted of nearly all of the most complex food molecules, many billions of protocells must have been in existence. As the most desirable food molecules become more and more scarce, some of the protocells would have disintegrated, themselves becoming food for the remaining intact protocells.

It is very likely that a sort of equilibrium would have developed, with protocells disintegrating and other cells absorbing their remains and reproducing, until a particular protocell acquired an enzyme or two that made it capable of utilizing a second, slightly less complex type of molecule still abundant in the primeval pool. Able now to tap an abundant new source of food, this new, mutant form of protocell would multiply rapidly until it replaced all the old-fashioned types that required the highly complex type of molecule now depleted from the medium. Before long, the second type of food molecule would have been used up, and competition would develop again, resulting in a protocell that could utilize a third, still simpler form of chemical food (see below).

MODEL OF SELF-SUSTAINING COACERVATIVE DROPLET: Would it be "alive"? The primordial soup in which life began contained a wide variety of organic compounds, ranging in size from very small to very large, energy-rich molecules. The large, energy-rich molecules (such as the hypothetical compound L×M is conceived to be composed of two major parts, L and M. Breaking the chemical bond holding L o M would liberate energy. This energy could immediately be used to join a phospate group (P) to a molecule of adenosine diphosphate (ADP), the nearly universal form of "energy currency" in modern cells. ATP is an energy-rich compound. Many of the substances in the soup would have had catalytic ability, i.e., the ability to speed up chemical reactions without themselves being used up in the breakdown of the food molecule L×M, with liberation of energy. Overall, this process can be summarized in an equation: Eq. 1. R + L×M + ADP + P => R + L + M + ATP At the same time it may be supposed that there existed in the soup certain compounds which were autocatalytic, i.e., able to assist in the sybthesis of more molecules like themselves. (Sidney Fox has shown that certain proteinoids can in fact facilitate the formation of more proteinoid, although it is not known wheter or not the new proteinoid is precisely the same as the old one.) In the model above the molecule X×Y is conceived to be autocatalytic, speeding up its own formation from its two major compounds X and Y, given a source of energy such as ATP. (When ATP gives up its energy, it is degraced back into phosphate and ADP.) Overall, this process can be summarized in a second equation: Eq. 2. ATP + X + Y + X×Y => ADP + P + X×Y + X×Y The hypothetical coavervate droplet shown above is conceived to consist of two phases, a matrix phase composed of X×Y and one or more particles of the catalyst R. In such a structure the chemical reactions described in equations 1 and 2 could be expected to take place at the phase boundary, where particles of R make contact with the X×Y phase. As the droplet synthesis more X×Ym it will grow in size until it becomes hydrodynamically unstable. Then it will break up into two or more daughter droplets. If the daughter droplets contain at least some R, they will be able to continue the life-like activity of the model. Further evolution of the system would involve gaining the ability to break L and M into still simpler waste produts, extracting ever more energy from their chemical bonds. (The end point would be reached when the food molecules could be broken down all the way to water and carbon dioxide.) Evolution would also involve acquiring the ability to synthesize X and Y form progressively simpler precursors, until only carbon dioxide, water, inorganic minerals, and sunlight were needed. Each of these evolutionary developments would require the addition of new catalysts (proteinoids, pigments, mineral ions, etc.) to the structure of the model above.

As the primordial soup thinned out into just plain ocean, with simpler and simpler molecules being depleted by the heterotrophic protocells, there came a point at which further reduction in the complexity of "food" molecules was impossible. At this point, our first true cells would be able to make do with just carbon dioxide, water, and inorganic minerals. These cells would have become the first autotrophs, organisms independent both of other organisms and leftover soup. These autotrophs would have been able to carry on photosynthesis, capturing the energy of sunlight and using it to combine carbon dioxide and water to form sugar. Sugar, in turn, could be reworked and combined with inorganic compounds containing nitrogen, sulfur, phosphorus, and other elements to form all the varied substances needed to maintain and improve the quality of what at this point must be called "life."

The Origin of Cellular Structure

As in the case with trying to decide how the chemicals of life came into being, when trying to decide how cellular structure came about we are faced by a surfeit of plausible possibilities. There appear to be more possibilities than we need.

Oparin was impressed by the ability of proteins and other macromolecules in solution to clump together to form suspensions of microscopic, complex droplets known as coacervates. As these particles drift about, they absorb more molecules from the surrounding solution and actually grow in size. When a certain size is reached, the coacervate particles reproduce, sometimes by a process that resembles the budding of yeasts, sometimes by simple, irregular fission. The daughter droplets, in turn, grow, split, grow, and split, until the raw material molecules are depleted from the medium. Oparin showed experimentally that many enzymes and groups of enzymes can form into coacervate droplets and can carry on metabolic activities - even imitating the activities of short metabolic pathways.

Sidney Fox of the University of Miami, on the other hand, has shown that when dry amino acid mixtures are heated, they polymerize into a protein-like material called proteinoid. Proteinoids are of great interest theoretically in that they frequently possess catalytic ability. They are able to catalyze not only the formation of nucleic acids (DNA or RNA) - they are autocatalytic as well, being able to bring about the formation of more proteinoid! In short, proteinoids exhibit a primitive reproductive ability.

In addition to possessing exciting chemical abilities, when brought into contact with water, proteinoids can form into structures suggestive of protocells. Termed "microspheres" by Fox, these microscopic particles also can grow by accretion, proliferate by means of fission and budding for several generations, and even engage in a form of interparticle communication by transfer of material.²³

Marigranules, discovered by the Japanese researcher Fujio Egami,²⁴ have also been offered as models of protocells. Egami discovered that by adding simple compounds such as formaldehyde and hydroxylamine (compounds formed easily under primitive-earth conditions) to seawater enriched with trace elements such as molybdenum, zinc, and iron, it was possible to bring about not only the formation of amino acids, lipids, and other biochemically important materials, but it was even possible to get the amino acids to polymerize into peptides and protein-like materials. Best of all, if allowed to stand for several months, seawater containing these polymers was found to contain tiny cell-like structures - marigranules. Unlike Fox's proteinoid microspheres, marigranules are bounded by a lipid membrane-like surface. The similarity of marigranule structure to ordinary cell structure is somewhat greater than that of microspheres. Like microspheres, marigranules are also capable of growth and undisciplined reproduction. Although they too possess catalytic properties, studies of marigranule "metabolism" have not yet progressed as far as those of Fox's microspheres.

Some time ago, at an annual meeting of the American Association for the Advancement of Science, David Deamer²⁵ of the University of California at Davis reported on studies he has done on materials extracted from the Murchison meteorite. Some of the lipid (fatty) material he extracted from the meteorite²⁶ was capable of self-assembly into membrane-bound vesicles looking very much like tiny cells. Like real cell membranes, Deamer's membranes were capable of incorporating pigment-like compounds, such as pyrene, and exhibited some catalytic abilities. It is reasonable to suppose that lipid membranes such as these, forming into closed vesicles as a result of the foaming action of waves, would have enclosed coacervate drops, proteinoid micro-spheres, and marigranules, and would have increased the complexity of protocells greatly. Most importantly, such composite, membrane-bound protocells would have been able to carry out a wide variety of different chemical tasks simultaneously, by virtue of the differing capabilities of their various components. The complexity and properties of such protocells would come very close to those of primitive cells.

Perhaps the most important feature of the protocellular entities discussed is that they would have been capable of evolutionary change by means of natural selection. Protocells acquiring useful combinations of protoenzymes and other useful materials would have tended to survive, and protocells lacking them would have tended toward dissolution. Fusion of protocells separately capable of important life functions could have let to broadly competent form with greater survival potential. Almost certainly, the principle of survival of the fittest" is older than life itself.

DNA: The First Shall Be Last

In all present-day cellular forms of life, DNA is the repository of hereditary information. It is the information stored in DNA which tells the difference between a man, a mouse, and a moss. In modern cells, DNA stands aloof from the metabolic fray, passing its instructions on to "messenger" RNA, which then brings about the synthesis of proteins - a process which is highly complex and is clearly the product of a long series of evolutionary developments. The set of rules which relates the "wording" of the DNA molecule to the amino acid sequence of proteins is known as the "genetic code."²⁷

It is generally agreed that DNA was not present in the first cells. Before the advent of DNA, RNA could have served as the genetic material in early cells, just as it still does in certain viruses. The question still remains, however, whether or not even more primitive cells could have existed without even RNA, using proteins as the major informational molecules. We have seen previously that Fox's proteinoids have the ability to form more proteinoid - thus theoretically being capable of forming a self-replicating system - and they also can catalyze the formation of DNA and RNA from their building blocks. Did life go through a protein phase before the evolution of the genetic code? Or are full-fledged proteins (as opposed to proteinoids, which are somewhat more irregular in their structure than proteins) possible only with a nucleic acid-directed system of protein synthesis?

A great deal of highly technical work has been published on the origin of the genetic code, and it is not possible to summarize it here. However, mention should be made of the astonishing suggestion made recently by A. G. Cairns-Smith that the DNA-RNA-Protein cycle of modern cells was preceded by primitive forms possessing none of the major biochemicals now characteristic of cells. According to Cairns-Smith, the first replicating systems were not even organic, they were minerals! Specifically, they were self-replicating crystals of clay. Shades of Genesis, chapter two!

Cairns-Smith makes it clear that clay crystals cannot only replicate, but can even transmit information from one crystal generation to the next. Crystal defects, the analogs of mutations, can be passed on from parent to daughter crystal. He shows that a type of natural selection can operate in populations of clay crystals, and that clay crystals quite easily could have begun to create and use organic substances to stabilize their micro environments and increase their chances of survival and reproduction. Since various clays are known which can catalyze the formation and polymerization of amino acids, mimic photosynthesis, and direct the formation of nucleic acids, it is only startling - not far-fetched - to suppose that a genetic-code assemblage of RNA and proteins might have been brought together on the surface of a clay crystal and, when just the right combination came about, could thereafter have subsisted without the aid of the clay substrate.

Cairns-Smith likens the delicately balanced nucleic acid-protein system to an arch. Just as the sides of an arch cannot be kept from falling without the aid of the keystone, and the keystone cannot be kept up without the aid of the rest of the arch, so too in living cells nucleic acids cannot come about without the agency of protein enzymes, and enzymes cannot be produced without the aid of nucleic acids.

To make an arch of stones needs scaffolding of some sort: something to support the stones before they are all in place and can support each other. It is often the case that a construction procedure includes things that are absent in the final outcome. Similarly in evolution, things can be subtracted. This can lead to the kind of mutual dependence of components that is such a striking feature of the central biochemical control machinery.²⁸

Whatever future research may show to have been the case with respect to clay minerals as the scaffolding that brought about the construction of the genetic code, it is quite clear that DNA - the prime minister of the biochemical government - was actually a late refinement and was not a part of the first cells.

Envoi

The most primitive living things that carry on photosynthesis do so without releasing molecular oxygen into the atmosphere. It is not clear just how long this type of photosynthesis dominated the earthly scene. By around 1.5 billion years ago, however, a number of photosynthetic algae had evolved which had developed a new, improved form of photosynthesis which released oxygen into the oceans and atmosphere. For early forms of life, oxygen was the first form of "toxic waste," and natural selection led to the development of enzymes (such as catalase) which could protect cells from the damaging effects of oxygen.²⁹ Ultimately, cells acquired the ability to turn adversity to advantage, and actually came to make use of oxygen as a means of "burning" their fuel (sugar and other simple molecules) to provide greatly increased amounts of energy with which to carry out various types of new activities.

Once it was possible, thanks to oxygen-based aerobic respiration, to generate large amounts of energy in very short amounts of time, cells could become more mobile, and the first single-celled animals became possible. Movement is the essence of animality, and significant, sustained movement was unaffordable before the harnessing of oxygen. It was the harnessing of oxygen that led to the appearance of the secondary heterotrophs, the animals. There is no free lunch in nature, and cells acquiring mutations allowing them to move easily about their watery world - making it possible to avoid harmful environments and seek out healthful ones, even in the dark when solar energy was unavailable - had to sacrifice the machinery needed to carry on photosynthesis. Instead of creating their own food from scratch, they could simply engulf their slower neighbors, digesting them by means of digestive enzymes they had evolved long before.

Once the pace of cellular motions had quickened into animal activity, the future course of evolution became clear, at least in its general outline. There would be a selective advantage for cells to group together to form multicellular organisms, animals big enough to procure and eat any of the primitive vegetation in the sea. Once herbivorous animals became abundant, natural selection would lead to the appearance of carnivores - animals which would generally have to be more mobile (and therefore more intelligent) than the herbivores.

Thus began the earliest version of the "arms race," which continues to this day. With carnivores preying upon herbivores, natural selection would tend to select for faster and smarter herbivores, making them harder for the carnivores to catch. This, in turn, would bring about selection for even faster and smarter carnivores. Ultimately, certain carnivores would evolve the ability to use and make tools — weapons with which to gain a decisive and irreversible advantage over the herbivores. Oxygen would be harnessed still a second time in the history of life - in the discovery of fire.

Homo sapiens would have been better named Homo prometheus, after the mythical hero who stole the fire of the gods and brought it to earth for the sake of us mortals. For human history in a profound way is the history of fire and the secondary technologies it has sparked; and science is a part of this history. With fire, Sidney Fox heats lava rocks, sprinkles them with amino acid solutions, and analyzes the proteinoids that form upon their surfaces. Stanley Miller passes sparks through primitive atmospheres to witness the formation of the chemicals of life. The electric sparks, of course, result from electric currents generated miles away by the coal and petroleum fires of generating plants. The fires of science flame brightly, thanks to the oxygen-generating process developed by humble algae so many eons ago - algae which now we seek to understand.

The question that Darwin could not have hoped to answer - the question that Newton, Galileo, and earlier geniuses could not even have dared to ask - is very close to being answered. Thousands of scientists in hundreds of laboratories are closing in on the problem of life's origin. It is exhilarating to contemplate the progress that has been made, despite the fact that the experimental study of biopoiesis is only slightly older than the memory of World War II. When I was born, some sixty years ago, hardly anyone could have suspected that the chemicals of life would prove to be ubiquitous and so easy to produce. When I graduated from college, no one could have suspected the ease with which protocell-like marigranules could form in seawater. And who would have expected to find the makings of cell membranes in meteorites?

Whether or not life as we know it is the result of a "genetic takeover" - of organic systems supplanting self-replicating mineral ones - or whether the genetic code had a yet unsuspected origin remains to be settled. But we shall learn the answer, and the answer is coming soon.

***

Formerly a professor of biology and geology, Frank R. Zindler is now a science writer. He is a member of the American Association for the Advancement of Science, the New York Academy of Science, The Society of Biblical Literature, and the American Schools of Oriental Research. He is the editor of American Atheist.

Notes

1 - Alexandr I. Oparin, Proiskhozhdenie Zhizni [The Origin of Life] (Moscow: Izd. Moskovskii Rabochii, 1924). Back

2 - Alexandr I. Oparin, Vozniknovenie Zhizni na Zemle, 1st ed. (Izd. Akad. Nauk SSSR, 1936); The Origin of Life on Earth, 3d English ed., trans. Ann Synge (New York: Academic Press, Inc., 1957). Back

3 - J. B. S. Haldane, "The Origin of Life," Rationalist Annual, 1928; Science and Human Life (reprint; New York and London: Harper & Brothers, 1933). Back

4 - Oparin, The Origin of Life on Earth, p. 79. Back

5 - Haldane, Science and Human Life, pp. 143-144. Back

6 - Harold J. Morowitz and Mark E. Tourtellotte, "The Smallest Living Cells," Scientific American, March 1962, pp. 117-126. Back

7 - There is a primitive form of photosynthesis found in certain bacteria which, although it can utilize light energy, does not produce oxygen as a by-product. Back

8 - Several definitions of reduction and oxidation can be found in the chemical literature. Originally, 'oxidize' meant adding oxygen, and 'reduce' meant adding hydrogen, usually to replace oxygen. A more modern, generalized definition of 'oxidize' includes removal of hydrogen or an electron from a molecule, and 'reduction' is their addition. Hydrogen-rich materials are said to be 'reduced.' Back

9 - It is important that these experiments reproduce natural conditions and processes in a manner requiring no intelligent guidance. Otherwise, such experiments are no improvement over theology! Back

10 - Although aluminum is of little importance in living things today, it (and silicon) may have been of great importance in the first almost-living systems, as we shall see in the final installment of this article. Back

11 - Altogether there are eight common nucleotides: four ribonucleotides, containing ribose sugar and being the building blocks of RNA, and four deoxyribonucleotides, containing deoxyribose sugar and being the building blocks of DNA. Both RNA and DNA contain the bases adenine, cytosine, and guanine, but in RNA uracil is substituted for the thymine found in DNA. Back

12 - ATP (adenosine triphosphate) is extremely important as the universal energy currency in modern cells. Energy gathered from the sun or produced from food is stored in the form of high-energy phosphate bonds in ATP. This energy can then be used to energize recalcitrant chemicals and make them do tricks that would be thermodynamically improbable without the cattle-prod of ATP. Back

13 - Kobayashi, K., et al., "Abiotic synthesis of nucleosides by electric discharge in a simulated primitive earth atmosphere," Origins of Life and Evolution of the Biosphere, Volume 16, Nos. 3/4 (1986), pp. 277-8. Back

14 - The letter L stands for the Latin word lævus, 'left,' and the D stands for dexter, 'right.' Back

15 - Folsome, Clair Edwin, The Origin of Life: A Warm Little Pond, W.H. Freeman & Co., San Francisco, 1979, p. 150. Back

16 - Schmeck, Harold M., "Clay on Shores of Ancient Seas Viewed as Key to Origin of Life," The New York Times, October 15, 1977, p. 26C. Back

17 - This page of the magazine contains information because of the highly nonrandom, yet relatively unpredictable way in which the elements we call letters are arranged on its surface. If one were to cut out all the words, shake them up, and pour them out on a blank page, the information content would be greatly reduced. If the words were cut up into individual letters and the letters strewn about at random, the information content would be all but lost. Likewise, a cell "contains" information by virtue of the way in which its molecular elements are arranged in space and time. The way in which DNA (the genetic material of the cell) contains information - with its four types of "letters" (A, T, C, and G) strung out to form long "messages" - is exactly analogous to the way this sentence contains information by virtue of the manner in which the letters of the English alphabet are laid out. Back

18 - Sidney W. Fox, The American Biology Teacher, vol. 43, no. 3, March 1981, p. 129. Back

19 - It will be remembered that porphyrin molecules have been shown to form spontaneously under primitive-earth conditions, and various types of porphyrins have been found in meteorites, objects formed in the solar nebula before the earth became a planet. Back

20 - In catalase, as in other enzymes, only a small part of the protein structure is involved in forming the so-called active site, the part of the molecule that actually carries out the chemical chores required buy the cell. Often, large parts of an enzyme are evolutionary refinements that will determine whether the molecule will be dissolved in the cytoplasm of a cell or be attached to cell membranes, determine the circumstances under which the enzyme will be active or inactive, etc. Of the hundreds of amino acids that make up a typical enzyme, it is usually the case that only a dozen or so of them are critically involved in its catalytic activity; and in the rest of the molecule it is often possible to make numerous amino acid substitutions without measurable altering the enzymatic activity. The first enzymes almost certainly were very small molecules, containing only the amino acid sequence essential for enzymatic activity. The smaller the enzyme, of course, the greater the probability it could have formed spontaneously. Back

21 - Alexandr I. Oparin, Proiskhozhdenie Zhizni [The Origin of Life] (Moscow: Izd. Moskovskii Rabochii, 1924). Back

22 - Because of the constraints of the Second Law of Thermodynamics, simple organic compounds would have been the most common components of the "soup," the most complex compounds the least common. The most complex molecules generally would have the highest information content and would be least favored from a thermodynamic point of view. Back

23 - Duane L. Rohlfing, "The Development of the Proteinoid Model for the Origin of Life," Molecular Evolution and Protobiology, ed. Koichiro Matsuno, Klaus Dose, Kaoru Harada, and Duane L. Rohlfing (New York: Plenum Press, 1984), pp. 29-43. Back

24 - Fujio Egami, "Chemical Evolution in the Primordial Ocean and the Role of Transition Element Ions" [in Russian], Izvestiya Nauk SSSR, Seriya Biologicheskaya, no. 4, 1980, pp. 519-526. Back

25 - David W. Deamer, "Amphiphilic Components of Carbonaceous Meteorites: Origins of Membrane Structure, "AAAS Abstracts: 14-19, January 1989, San Francisco, p. 24. Back

26 - It should be remembered that many meteorites contain primordial material created in the solar nebula even before the formation of the earth. Finding membrane-forming materials in meteorites is very good evidence that similar materials would have been present on the nascent earth. Back

27 - The genetic code is often confused with the genetic message. The genetic message is the entire information content of the DNA molecule - the recipe it contains. The genetic code is the rule of correspondence between DNA structure and protein structure. Back

28 - A. G. Cairns-Smith, Seven Clues to the Origin of Life: A Scientific Detective Story (Cambridge University Press, 1985), p. 115. Back

29 - Oxygen, because of its high chemical reactivity, is like a bull in a china shop when it runs loose in the cell. Unless its movements are carefully directed, it is likely to attack and ruin many of the informational molecules of the cell. It can even kill the cell. Back

The publishing was authorized by the author of the original essay.

The original essay is available at February, March and April 1989, American Atheist Magazine

Translations to spanish and grammar corrections on the translation to portuguese are welcome.