Genesis: The Scientific Quest for Life's Origin

by Robert M. Hazen

  Freund had won relatively few converts by the summer of 2003, when he came to George Cody's lab to duplicate his extraction of molecules from olivine. For several weeks, a white-coated Freund was an amiable fixture at Cody's lab bench. He meticulously washed and powdered the semiprecious stones, extracted carbon compounds with strong solvents, and analyzed the samples with Cody's battery of high-tech instruments. Sure enough, every crystal seemed to release a small hoard of carbon-rich molecules. There wasn't much, certainly, but the volume of igneous rock that has formed and eroded over the course of geological history is immense. So, by Freund's estimates, solid rocks have provided one of Earth's largest and most continuous sources for the emergence of biomolecules.

  Scientific progress involves a long process of hypothesis and testing, bold claims, and critical counterarguments. Not surprisingly, Freund's hypothesis has received a lot of scrutiny and not a little disdain. But those unexplained carboxylic acids can't be ignored. And so, for the time being, the jury is still out.

  THE MULTIPLE-SOURCE HYPOTHESIS

  Where did life's crucial molecules form? In spite of the polarizing advocacy of one favored environment or another by this group and that, experiments increasingly point to the possibility that there was no single dominant source.

  It's not a matter of Millerites versus ventists, or deep space versus Earth's surface. Many ancient environments boasted carbon atoms and sufficient energy to initiate their chemical transformations. Many environments must have contributed to the prebiotic inventory. Lightning-sparked gases were a major source, to be sure, as were UV-triggered reactions high in the atmosphere. Deep in the ocean, in environments ranging from lukewarm to boiling hot, molecules must have been made in abundance, as they certainly were within some reactive rocks of the crust (and, if Tom Gold is correct, perhaps in the much deeper mantle). A wealth of organic products also rained down from space, formed in remote dense molecular clouds and concentrated in the carbon-rich meteorites and asteroids that coalesced to make our planet.

  The bottom line is that the prebiotic Earth had an embarrassment of organic riches derived from many likely sources. Carbon-rich molecules emerge from every conceivable environment. Amino acids, sugars, hydrocarbons, bases—all the key molecular species are there.

  So the real challenge turns out to be not so much the making of molecules, but the selection of just the right ones and their assembly into the useful structures we call macromolecules. That process required a higher level of emergence.

  Interlude—Mythos Versus Logos

  People of the past … evolved two ways of thinking, speaking, and acquiring knowledge, which scholars have called mythos and logos. Both were essential.

  Karen Armstrong, The Battle for God, 2000

  “Whoa, wait a minute!” My wife, Margee, sets aside my draft, her expression a cross between confusion and exasperation. “Is any of this stuff true? Who's to say you're not just writing another creation myth?”

  “What do you mean? This is science.” How could she miss the point? “There's a big difference between myth and science!”

  “But you're just making up a story. It's really ancient history—no one will ever know for sure how life started.” She's warming up to the debate. “Besides, you're constantly saying ‘We don't know' and ‘The jury's still out.' Can you be sure about anything?”

  “Gimme a break!” was about the cleverest comeback I could think of, as I turned back to the word processor.

  So which is this book? Logos? Mythos? Some combination of the two? Am I writing the truth, or only just-so stories?

  The distinction is not always clear-cut. The studies of life's origin are in some ways like the efforts of archaeologists to document the history of ancient Troy. Troy fell to the Greeks in about 1190 BCE and eventually was buried under the litter of later cities. Real people were born, led their lives, and died in Troy; nevertheless, most of that rich, poignant history is lost forever. We learn fragments of the truth from excavations, artifacts, and ancient documents. But mythology always lurks in the background. The Iliad, the Odyssey, and the Aeneid inevitably color our understanding of the great city's past.

  Life, too, emerged through some real process. Molecules formed, they combined, they began to replicate. Much of that history is also lost forever. We will never know exactly where or when the first living entity arose, nor is it likely that every chemical detail of the process will ever be known for certain. Scientists flesh out the process with their own favorite origin stories: Miller's primordial soup, Gold's deep hot biosphere, Wächtershäuser's sulfide surfaces. We tend to favor the stories told by our friends or our mentors, while discounting those of our rivals. And even if we do succeed in making life in the lab, there's no guarantee that that's exactly the way it happened 4 billion years ago.

  Nevertheless, science and myth differ in a fundamental way. Scientific stories must win support through logically sound theory, rigorously reproducible lab experiments, and independently verifiable observations of nature. A scientific hypothesis must make unambiguous predictions. If those predictions fail, the story is deemed false by the scientific community and is cast aside. Today we may debate the details of the process, but all scientists agree that there must be a true origin-of-life story. That truth is our common goal.

  There's so much we don't know and, as you have undoubtedly noticed, much of this book is qualified with phrases of uncertainty. Hardly an experiment or theory goes unchallenged, and groups of researchers often reach diametrically opposed conclusions. But we have attained a vibrant stage in origins research, one in which we are increasingly aware of what we don't know and, consequently, are increasingly focused on what we must learn. A sustained, confident international program of research has supplanted the naïve optimism of the 1950s and 1960s. And so the scientific stories come thick and fast as theory, experiment, and observation winnow the universe of possibilities.

  Part III

  The Emergence of Macromolecules

  The beginning and end points of life's emergence on Earth seem reasonably well established. At the beginning, more than 4 billion years ago, life's simplest molecular building blocks—amino acids, sugars, hydrocarbons, and more—emerged inexorably through facile chemical reactions in numerous prebiotic environments, from deep space to the deep crust. A half-century of compelling synthesis research has amplified Stanley Miller's breakthrough experiments. Potential biomolecules must have littered the ancient Earth.

  The end point of life's chemical origin was the emergence of the simple, encapsulated precursors to modern microbial life, with all of life's essential traits: the ability to grow, to reproduce, and to evolve. Top-down studies of the fossil record hint that such cellular life was firmly established almost 4 billion years ago.

  The great mystery of life's origin lies in the huge gap between molecules and cells. Ancient Earth boasted oceans of promising biomolecules but, like a pile of bricks and lumber at a building supplier, more than a little assembly was required to achieve a useful structure. Life requires the organization of just the right combination of small molecules into much larger collections—macromolecules with specific functions. Making macromolecules from lots of little molecules may sound straightforward, but what most books don't mention is that for every potentially useful small molecule in that prebiotic environment, there were dozens of other molecular species with no obvious role in modern biology. Life as we know it is incredibly picky about its building blocks; the vast majority of carbon-based molecules synthesized in prebiotic processes have no obvious biological use whatsoever. That's why, in laboratories around the world, many origins researchers have shifted their focus to the emergent steps by which just the right molecules might have been selected, concentrated, and organized into the essential structures of life.

  10

  The Macromolecules of Life

  To purify and characterize thoroughly all [biomolecules] would be an insuperable task were it not for the fact that each class
of macromolecules … is composed of a small, common set of monomeric units.

  Lehninger et al., Principles of Biochemistry, 1993

  We are chemical beings. Every living organism, from the simplest microbes to multicellular fungi, plants, and animals, incorporates thousands of intricate molecular components. All of nature's diverse life-forms grow, develop, reproduce, and respond to changes in their external environment—vital tasks that must be accomplished by exquisitely balanced cascades of chemical reactions.

  The more biologists learn about life, even the most “primitive” single-celled organisms, the more amazingly complex life seems to be. Everywhere you look, living entities have found their niche, and they survive in wonderfully varied ways. Indeed, in a sense, chemical complexity seems synonymous with life. Yet emergent systems, however complex, are usually built from relatively simple parts, and life is no exception.

  One of the transforming discoveries of biology is that all known life-forms rely on only a few basic types of chemical reactions, and these reactions produce a mere handful of molecular building blocks. Virtually all of life's essential construction materials are carbon-based organic molecules that combine by the thousands to form layered enclosures or chainlike polymers. In every instance, just a few kinds of small molecules assemble into a great variety of larger structures.

  In the early nineteenth century, conventional wisdom held that life's chemical compounds formed by their own mysterious rules, perhaps governed by a “vital force.” Many scholars assumed that the nascent science of chemistry applied only to the inorganic world—the world of rocks, minerals, and metals. This perception changed in 1828, when the young German chemist, mineral collector, and gynecologist Friedrich Wöhler demonstrated that biological molecules are no different in principle from other chemicals. He combined the common laboratory reagent cyanic acid with ammonia and succeeded in producing urea, which is extracted in the kidneys and found in urine. Wöhler's letter announcing his important discovery displayed a sense of whimsy not always associated with German academicians: “I can no longer, as it were, hold back my chemical urine: and I have to let out that I can make urea without needing a kidney, whether of man or dog.” By employing straightforward lab techniques to produce a chemical substance known only from life, Wöhler convinced his colleagues of the ordinariness of organic chemistry.

  MODULAR LIVING

  Perhaps the most distinctive characteristic of the molecules of living organisms is their modular design. This familiar strategy is similar to that of modern architects, who rely for the most part on standard building materials. They use mass-produced bricks, beams, windows, doors, stairs, lighting fixtures, and so on to assemble an almost infinite variety of commercial and private buildings.

  You don't have to build in that way. A multimillionaire acquaintance recently created the most extraordinary mansion, with every square foot of walls and floor, every light and bath fixture, every door and window custom-designed and hand-crafted. It's an amazing house, with secret passages, unexpected nooks, and hidden closets, all lovingly constructed of the finest woods, stone, and other extravagant materials. Such personalized craftsmanship is wonderful to see, but inordinately expensive. Most of us choose a more economical path. By relying on a few standard construction modules, buildings are faster and cheaper to design and build. But modularity doesn't imply uniformity. You can design a unique dwelling of almost any size or shape from simple components available through any hardware or building supply store.

  The same modular principle holds for life's carbon-based molecular building blocks. Four key types of molecules—sugars, amino acids, nucleic acids, and hydrocarbons—exemplify life's chemical parsimony.

  Sugars are the basic building blocks of carbohydrates, Earth's most abundant biomolecules. Many common sugars in our diets, including the fructose of honey, the sucrose of cane sugar, and the glucose of fruits, are small molecules consisting of at most a few dozen atoms. These energy-rich molecules incorporate carbon, oxygen, and hydrogen typically in about a 1:1:2 ratio. But most of life's sugar molecules are locked into macromolecules—countless individual sugar molecules linked together to form giant polymers, such as the fibrous cellulose of plant stems or the bulky starch of potatoes.

  Amino acids are small molecules that link together to form proteins. Proteins serve as the chemical workhorses of life, with myriad vital functions: They form tissues and strengthen bone; they act as hormones to control glandular functions; they clot blood, digest food, and promote the thousands of chemical operations essential to life. All proteins form from long chains of hundreds to thousands of individual amino acid molecules, lined up like beads on a string. These chains fold into the most wonderful shapes, each protein folded in such a way as to accomplish a specific chemical task.

  The vital genetic molecules DNA and RNA are also lengthy chainlike polymers, assembled from small molecules called nucleotides. Each nucleotide, in turn, is constructed from three small molecular parts: a 5-carbon sugar (ribose in RNA, its cousin deoxyribose in DNA); a base (one of five closely related ring-shaped molecules); and a phosphate group (a tiny cluster made up of a phosphorus atom surrounded by four oxygen atoms). RNA consists of a long chain of single nucleotides, while in DNA two such chains link together and twist into the famed “double helix” structure.

  Finally (as we'll see in the next chapter), arrays of elongated hydrocarbon molecules called lipids, including a wide variety of fats and oils, coalesce in every cell to form membranes, store energy, and perform other critical functions.

  The most enticing aspect of Stanley Miller's experiment and the discoveries of subsequent prebiotic researchers was that they synthesized components (or at least close relatives) of all four groups—carbohydrates, proteins, nucleic acids, and lipid membranes. No wonder so many researchers were optimistic that an understanding of life's emergence was at hand.

  But this molecular catalog of success ignores a puzzling part of the prebiotic synthesis story. For every useful molecule produced, many other species with no obvious biological function complicate the picture. Take sugar molecules, for example. All living cells rely on two kinds of 5-carbon sugar molecules: ribose and deoxyribose. Sure enough, several plausible prebiotic synthesis pathways yield small amounts of these essential sugars. But for every one of these molecules produced, many other 5-carbon sugar species also appear—xylose, arabinose, and lyxose, for example. Adding to this chemical complexity is a bewildering array of more than 100 3-, 4-, 6-, and 7-carbon sugars, in chain, branching, and ring structures—of which life uses only a small handful.

  As if that weren't enough of a problem, life is even choosier about its molecules. Many organic molecules, including ribose and deoxyribose, come in mirror-image pairs. These left- and right-handed varieties are in most respects chemically identical. They possess the same chemical formula and many of the same physical properties—identical melting and boiling points, for example. But they differ in their shapes, just like your left and right hands. Laboratory synthesis usually yields equal amounts of left- and right-handed sugars, but finicky life employs only the right-handed sugars, never the left.

  Given the disparity between the rich variety of prebiotic molecules and the apparent paucity of biomolecules, is it possible that we're fooling ourselves? Might the earliest life-forms have used a more diverse suite of organic molecules and a different repertoire of biochemical pathways? It turns out that living cells hold clues that are now being teased out by the remarkable field of molecular phylogeny.

  MOLECULAR PHYLOGENY AND THE “LAST COMMON ANCESTOR”

  The complete chemical arsenal of each living species is recorded in its unique genome, an encoded sequence of millions to billions of DNA “letters,” the base pairs that form the rungs of DNA's double helical ladder. The four-letter DNA alphabet—A, G, T, and C (for the purines adenine and guanine and the pyrimidines thymine and cytosine)—is sufficient to spell out all the genetic information of any organism. What's mor
e, all cells share the same mechanism for converting genetic instructions into the proteins that serve in many chemical and structural roles. That's why genetic engineers can use a simple bacterium, such as E. coli, to synthesize human growth hormone, or insulin, or other valuable pharmaceuticals.

  A central assumption of molecular phylogeny is that the genomes we see today evolved over billions of years from earlier ancestral cells, via the gradual mutation of DNA sequences. Comparative examination of many genomes reveals marked similarities, as well as important differences that have inexorably arisen by this slow evolutionary process. Differences among DNA sequences suggest the evolutionary branching; the more dissimilar the sequences of two species, the longer ago they are likely to have split from a common ancestor. DNA sequences that show little variation among many diverse species (so-called highly conserved sequences) are more likely to represent ancient, essential biochemical traits.

  The power and promise of phylogenetic analysis is epitomized in a remarkable recent study of early English literature. University of Cambridge biochemists Adrian Barbrook and Christopher Howe teamed with British literary scholars to analyze 58 different fifteenth-century manuscript copies of the Wife of Bath's Prologue from Geoffrey Chaucer's The Canterbury Tales. No copy of the late fourteenth-century original in Chaucer's hand is known, and significant variations among the many early hand-copied sources raise doubts regarding the author's original text.