Busy Being Born: On the Molecular Origins of Life Print E-mail

18kand_1-650(San Diego Reader September 12, 2002)

Ask evolutionary biologist Christopher Wills and organic chemist Jeffrey Bada, who are studying the origin of life on earth at the University of California, San Diego, to define life and both will answer, "an autonomous self-replicating system that replicates imperfectly via natural selection." Key for this pair is understanding how the abiotic or non-living world developed into the biotic one. Co-authors of The Spark of Life: Darwin and the Primeval Soup (2001), Wills and Bada believe life could arise only in optimal conditions and over a significant period of time.

Bada echoes Wills. "When I talk to the lay public about the origin of life, I’m talking about something that can’t be seen even with the best microscope."

The mid-western Bada, who is in his 60s and has taught at Scripps Institution of Oceanography since 1970, concentrates on the chemistry of amino acids in marine environments and on exobiology, the search for extraterrestrial life—not Klingons but unseeable organic compounds that have evolved "in the solar system and beyond." For the past 10 years, Bada has directed NASA’s Specialized Center of Research and Training in Exobiology, a program whose goal is to find "the importance of extraterrestrial input on the primitive Earth."

And yet as impressive as their bios are, both men still face a monumental problem. If biological evidence that developed during the Earth’s first billion years has been ground to dust in the maws of the planet’s tectonic plates, how can we be reasonably sure that life originated in one particular way? The answer is, we cannot be sure—not scientifically. We can only hypothesize.

Part of the trouble in Origin City comes from how we think about origins as a culture. The popular (and paltry) imagination sees origins in facile mechanistic terms, like a car equipped with an ignition switch. In her 1818 novel Frankenstein Mary Shelley never shows us Victor Frankenstein creating the eponymous monster. Her Promethean doctor assembles his Creature from pieces of corpses but is never seen to flip any switch. Instead, he merely states, "After days and nights of incredible labour and fatigue, I succeeded in discovering the cause of generation and life; nay, more, I became myself capable of bestowing animation upon lifeless matter." About the only science the occult-driven Frankenstein engages in is galvanism—the 19th century conceit that beings could be helped, even brought to life, via electric current.

The origin of life has also been "explained" as either inexplicable or divine, limbs of the same body. The Bible and other tracts—philosophic, spiritual, religious—argue that there’s no argument as to how life got started: God did it (quickly not slowly), and that’s that. Lack of evidence seems to make a purposive creation more probable.

Until the past two decades, simplistic explanations of life’s origin have guided scientists. An agnostic Darwin ends his Origin of Species by writing that "the Creator" breathed life "originally into a few forms or into one." That hardly sounds like an evolutionist. Up to and during Darwin’s time, scientists and theologians believed life sprung into being via spontaneous generation, which is similar to galvanism. Frogs born of the mud they wallow in, for example. I recall hearing the news conference, two days before the July 20, 1969 moon landing, during which Wernher von Braun, the German rocket engineer, said that the feat was "equal in importance to that moment in evolution when aquatic life came crawling up on the land" (italics added). In the 2000s, a smattering of researchers, among them Michael Behe, have bivouacked a new anti-evolutionary camp called "intelligent design." The group contends that evolution could not have built a system as sophisticated as a first cell. It is, in Behe’s words, "irreducibly complex." Any structure that exceptional had to have sprung fully formed. In short, a miracle.

There’s nothing miraculous about the United States income tax code. The code is a self-enabling system that no one understands except a certain caliber of tax attorney, who alone is capable (to our benefit and peril) of managing its recondite regulations. Even (former) Secretary of the Treasury Paul O’Neill hires a tax accountant. The tax code can be said to have "a life" because it is so highly complex and evolved. In fact, its complexity is the result of its development, a 90-plus-year accretion of more (never fewer) regulations. The tax code didn’t happen over night and it certainly wasn’t intelligently designed.

As the tax code did in one century, life seeped into being during its 10 to 200 million-year prime. Wills has called this variable interval no more than "a moment." But it is a moment that, in his thinking and research, he has tried "to blur," propounding a series of stages and a number of locales—in the molecular world and on the earth’s surface—for creation to begin. To shape the multiple endeavors of life—breeding, mutation, survival—only a process is possible. Not a birth, but a very slow arrival.

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Around 14 billions years ago, the universe originated with the Big Bang. Seven billion years later our solar system began to form. The materials which would become the earth accumulated: from space dust, gases, meteorites, and comets comprising frozen gases and ice. Eventually, the planet orbed into a sphere and its circling around the sun became fixed by gravity.

As the planet formed, the continual volley of meteorites and the decay of the planet’s radioactive elements created intense heat. In such heat, heavier elements sank. The core that drew down iron and nickel was, itself, soon bounded by a lower-density mantle. The silicates rose or stayed on the surface and, eventually, the surface cooked up a crust. The heat and pressure on the crust, however, was so great that it cracked into plates. The mantle’s circulating heat, called convection currents, pushed the plates—inches over centuries. This snail-paced but inexorable drift would form and separate continents.

Toward the end of the Hadean period, meteorites slowly stopped bombarding the earth. Free from assault, the crust solidified. The earth’s atmosphere developed, coalescing at first into a smoggy concentration of hydrogen, methane, ammonia, and water vapor, which nearly blotted out the sun. Hydrogen, the lightest element, escaped into space, and methane and ammonia, supplied from outgassing volcanoes, became unstable and converted to carbon dioxide and nitrogen. Regulating the build-up and retention of the atmosphere was the relative size of the earth and its gravity. Had the earth been smaller, even the heaviest gasses would have leaked into space.

Without meteor showers, the earth began to cool. In the atmosphere, water vapor condensed and fell as rain. During a deluge that lasted more than 100,000 years, the planet’s surface depressions flooded, and global oceans were formed. The crust, much of it now underwater, hardened as it inched along, while in the downpour the heavier elements gravitated to the ocean basins. The creation of the oceans was fundamental to the onset of life.

Wills and Bada describe the early earth as a "water world," punctuated by emerging land areas on which "mighty tides" washed in and out. "On islands that happened to stand athwart these massive movements of water," they write, "the tides could easily have swept across far wider regions than would be accessible to the tides of today." They believe these "enormous tidal floods" may have moved "in predictable patterns." And here, in the tidal washing of the land’s surface, the "synthesis and sorting of organic compounds" began.

Organic compounds, common to all living organisms, are substances that contain carbon. Atoms of carbon most often bond with atoms of hydrogen, nitrogen, or oxygen, and create an almost endless variety of compounds. Amino acids are organic compounds, which, when linked, form proteins. Twenty amino acids are found in living organisms. Just as amino acids build proteins, nucleobases—another kind of organic compound—build the large molecules DNA and RNA.

Scientists speculate that organic compounds may have originated in the oceans, from outer space, or in an oil slick that once covered the earth. Organic compounds may have arisen from hydrothermal vents, or undersea openings, where the crust is thin and superheated water produces chemical reactions. They may have ridden in on particles of cosmic dust, which have been showering the planet throughout its existence. We know today that organic compounds piggyback to earth on meteorites. A meteorite that fell near Murchison, Australia, in 1969, contained several of the building blocks of life, including amino acids and some of the nucleobases in DNA and RNA. It is these meteor-moored compounds that Bada has explored on this planet and plans to investigate in 2011 when soil and rock samples are returned from Mars. Bada, who has helped design the module that will retrieve those samples, hopes to uncover evidence of simple molecules on Mars that may have contributed to the building blocks of life on earth.

The third source of organic compounds may have been a planet-wide oil slick several meters thick. "The most abundant component," Wills and Bada write, "must have been tarry material," which, "tended to coagulate into gooey lumps or films." They describe the surface of the earth as "one giant Exxon Valdez disaster." The slick "could have been like a giant time-release capsule, continuously supplying adenine and amino acids to the oceans of the early Earth." Eventually, the oil would have "congealed into tar and then been broken down slowly by sunlight." But the ocean would have retained the organic compounds created in the tar.

Whether synthesized here or flown in from elsewhere, this grand stew of organic material was cooked during what’s called the prebiotic period, a post-Hadean time some 200 million years long.

Could it be that finding the right balance among the oceans, the island chains, the atmosphere, and the size and gravity of the earth was necessary for life to begin? Wills and Bada say this may be part of the equation. They cite the Gaia hypothesis, formulated in 1975 by British chemist James Lovelock and American biologist Lynn Margulis, and named for the Greek goddess of the earth. Gaia suggests that earth is a biosphere where carbon-rich sediments and a carbon-cycling system regulate the temperature. "Variations on the Gaia theme," write Wills and Bada, "may account for the Earth’s apparent ability to keep to a narrow range of temperatures as the Sun has gradually warmed over the last four billion years." But this hypothesis only works with "living organisms": Protoorganisms had to evolve before the earth became self-regulating. Indeed, for millions of years, the first life-creating system, in order to reach some level of organization, had to battle a severely inhospitable terrestrial environment.

***

As collaborators, Christopher Wills and Jeffrey Bada are working in what may be a golden age of life sciences at UCSD. The campus has nurtured a host of chemists and biologists who continue to hothouse new ideas about life and its origins. The most celebrated pair of UCSD biochemists are Stanley Miller and Harold Urey (Miller died in 2007; Urey in 1981). Under Urey’s tutelage, Miller, while a graduate student at the University of Chicago in 1953, synthesized amino acids by replicating the supposed prebiotic conditions of the earth—several gasses (hydrogen, ammonia, methane), a little water, an electrical charge, and no oxygen—in a bi-level rigging of glass flasks. Having taught at UCSD since 1958, Miller has, among other things, worked on dating the origin of life within a 10-million-year time-frame. (The Spark of Life is dedicated to Miller.) Nobel laureate and double helix codiscoverer Francis Crick researched genes at the Salk Institute until his death in 2004. Also at Salk is Sydney Brenner, who discovered, with Crick and others, messenger RNA, a genetic strand that orders the amino acids in proteins. Still another Salk veteran was Leslie Orgel (died in 2007), who made nucleic acid polymers and is researching a "first gene" that copied itself before complex protein catalysts evolved. And Gustaf Arrhenius of Scripps Institution of Oceanography, having collected carbon isotope evidence from rocks in Greenland, claims that life has existed for 3.8 billion years.

Each of these scientists has struggled with Wills’s "infuriating" question about the origin of life: How did organic molecules "come together" to make a protoorganism?

Some scientists, like Leslie Orgel, argue that one day there appeared a "naked gene on the beach," which had already fully formed in the oceans or on "the surface of some mineral particles." It’s been proposed that this gene, Wills and Bada write, "was capable of making copies of itself from the building blocks supplied by the primordial soup. . . . The genetic material grew in size and complexity, coding for more and more compounds, with which it surrounded itself." Wills and Bada, however, discount this theory. They believe "a limited amount of organization" had to have "appeared in the molecular world" before genes developed.

Another idea is that life sprung into action in what Bada portrays as a "self-sustained little chemical factory." The enclosed factory would have been composed of only metabolizing molecules. But Bada disagrees that such an isolated structure could have advanced and labels the idea, "life as we don’t know it."

Wills and Bada contend that the molecular precursors of a first self-replicating entity rooted themselves on the shores of a vast percolating ocean-soup. For millions of years, organic compounds had gathered in the soup. The compounds were then splashed for millions of more years onto the intertidal zones of the emerging land masses. There, in the tidal zones, formed what Wills calls an "ill-smelling residue," a mineral-rich "organic scum." This scum would have settled in nooks and crannies on the rocky shore.

As more and more molecules aggregated in the scum, organic compounds would have begun to produce more complex groups. For example, write Wills and Bada, "in those early tidal flats, wherever amino acids and sugars were concentrated," a "brownish polymer," or repeating chain of a simple molecular group, would have formed. The "accumulating sugars could have provided some sort of protective function—perhaps by producing a slimy impervious layer that would have repelled water as tides and waves periodically swept by." Such a layer might have separated groups of molecules.

One kind of protective layer that Wills and Bada believe developed early on was a two-dimensional-like membrane. This membrane wasn’t like the lipid or water-insoluble surface that houses a cell today. It was a barrier between one group of molecules and another. Bada describes the membrane as "sticky yet discrete," allowing for simple separation, and Wills elaborates. These membranes were probably "made of a silky material that floated about in the primitive soup. They would have had [the equivalent of] an inside and an outside, across which charged differences could be generated. [This would have led] to the charging up of these molecules." Perhaps the membrane’s surface was composed of one-half an amino acid that is negatively charged, which then attracts—to interact or bond with—a surface of positively charged aminos. Charged molecules may have combined and grown into energy-rich compounds that became sources of food for other compounds.

With the mix of ocean surf and the deposit of more and more organic molecules in the tide pools, "billions of tiny experiments" in life-making got going. Wills and Bada hold that tidal action, an agent itself of constant change, is essential to these experiments because on and within the scum favorable and unfavorable aggregates of molecules began to be sorted. Usually we associate a sorting-out process of favorable and unfavorable—the fit and the less fit—with evolution. But Wills and Bada suggest that "the sorting-out capability could somehow [have been] decoupled from the reproductive capability" before life began, in what they describe as "the molecular equivalent of birth and death." They believe the stronger molecules stuck to the rocks and "lived" while the weaker molecules got washed into the ocean and "died." Initially, there was a simple piling-on of molecules. In the piles, however, "different collections of molecules would have clung to different types of particles" on the rocky surfaces, eventually "becoming stratified according to their sizes and chemical properties."

These different collections, still being sorted out, resided in what Wills and Bada call a "molecular ecosystem." Supported by this ecosystem, a given robust collection of molecules may have been able to accomplish several things at once: attract, with its stickiness and its charged surfaces, other molecules coming in with the tides; absorb energy from sunlight that would aid its development; and protect its expanding aggregate from the ultraviolet light that would normally fry anything exposed.

***

We are now almost ready for the arrival. But, due to further complex development of the first living organism, it may be easier to describe the newborn before analyzing its composition. Wills and Bada adopted the term protobiont, used by the Russian biochemist Aleksandr Oparin in his 1926 The Origin of Life, to describe the first self-replicating entity in the molecular ecosystem. The protobiont has several characteristics: it is an organized collection of molecules; it can multiply "inside the complex, slimy layers of molecules" that cling to the rocks; and it carries rudimentary genetic information. The genes both house the protobiont’s hereditary characteristics and transmit instructions for self-duplication.

Wills and Bada believe that the protobionts made a "skeleton," or platform, out of a group of molecules. The platform secured itself by selecting (and affixing) the architecturally strongest organic compounds from the primitive soup. To illustrate this link between protobiont and environment, Wills offers—from much further up the evolutionary ladder—the sea snail. With the calcium carbonate molecules of seawater a snail builds a shell, a structure or platform within which it can survive. "The ability to build the shell is coded in the snail’s genes," he says, "but the shell itself isn’t." The shell’s materials must come from "outside the organism to enable the organism to complete itself." In this way, the protobiont needed the village of its environment in order to be raised.

The protobiont may have also contained what Wills and Bada describe as a "fragment of genetic material [which was] made up of a short piece of nucleic acid or a similar molecule." Whatever that genetic material was, it was like DNA, the nucleic acid common to almost all life today. We recall that DNA’s structure, the familiar spiraling double helix, is also like a zipper. The sides of the zipper interlock, linking nucleobases into base pairs: adenine with thymine, guanine with cytosine. The human genome is built of 3.2 billion base pairs; the tiny bacterium, mycoplasma, has 500,000 base pairs. Bada believes the first entity’s structure contained just 30 to 50 base pairs. That was "the minimal size needed to store information in this molecule. And, remember, it’s the sequence of the bases that stores the information." As more bases linked, the entity would have had more data to copy and more opportunity to mutate.

What information might have been stored first in the entity’s code? Wills and Bada write that the "most primitive distinction that the early genetic code must have made was between water-loving and water-hating amino acids." If a molecule was coded to "love water," then it would have readily received organic compounds from the soup. If a molecule was coded to "hate water," then it would have built up a structure to repel water, helping the entity survive some of the ocean’s pummeling action on the shores. As we have seen before, the two kinds of molecules may have allowed the entity to do two life-enhancing things simultaneously—grow and protect its growth.

One final sorting-out process remains—what Wills and Bada call, imperfect replication. It’s essential to remember that our knowledge of prebiotic chemistry is, as Wills laments, "full of so many missing steps [that] it’s difficult to see how these steps might have happened." It must have taken billions of chances for each step to occur—for cosmic dust, hydrothermal vents, and a planet-wide oil slick to seed the primeval soup with organic compounds; for ocean tides to begin pummeling the shores; for organic compounds to stick and polymerize in the scum; for the protobiont to develop fledgling nucleic bases that would remember bits and pieces of themselves across a generation. The final step necessary for self-replication would have been for the protobiont to evolve from copying a small part of itself to copying enough of itself that it passed on a living and autonomous organism.

"Life can’t get anywhere," Wills says, "if organisms make exact copies of themselves." In order to get somewhere—that is, to survive the severity of its environment—the protobiont was forced to adapt. The primary source of adaptation for the protobiont came through mistakes made while its genetic information was passed on. We may grasp the theory of the protobiont, Wills says, by looking at "the process of DNA replication itself. DNA is comprised of two strands that spiral, or grow, with each other in the double helix. Suppose you have a sequence of pairs that is A T. If the self-replicating DNA makes a mistake and puts a G in place of the T, you have A G, or a mutation. In this way, organisms acquire mutations and natural selection sorts these mutations out. Humans," he continues, "are very good at repairing our mistakes. We have all kinds of machines in the cell that repair mistakes. As a consequence, we don’t have anywhere near the number of mutations per unit time as the bacteria does."

Early on, the protobionts were, like bacteria, mutating at a very high rate. In fact, before the protobiont became a living organism, different sections of its genetic code, Wills says, must have "replicated extremely imperfectly." At first the protobiont retained a very small percentage of its precursor’s genes, which would not have specified "all the information needed for a living organism." To retain more genes, the protobiont may have evolved a better self-replicating system in which it reduced the number of its mistakes. But once the protobiont had stabilized its rate of mistakes, and enough genetic information was being copied to "secure" its autonomy, then, as Wills and Bada write, this "would have represented the first stirrings of life."

***

How long did it take for the protobiont to arrive? If protobionts were bacteria-like in their mutative proliferation, wouldn’t that have meant an extremely long time to evolve? Wills says no. In fact, he believes life got going in less than 10 million years. He cites three reasons.

One is an idea developed by Stanley Miller. Miller has written that "life must have arisen in 10 million years or less based on the known rate of decomposition of organic compounds." In this inferno, organic molecules "died" when, returned to the ocean, they were sucked through the hydrothermal vents in the deep-sea trenches every 10 million years.

Second is that, at the molecular level, chemical reactions take place very quickly. Combine this rapidity with the third reason: the growing shoreline space of the young planet. While the protobiont was using its 10 million years to form and replicate, it also formed and replicated in several billion places—those tiny terrestrial niches where organic scum collected. If incipient life had only one chance in a million billion chances in one locale, the likelihood of its developing is very slim. But if that one chance had a million billion molecular eco-systems within which to experiment, the odds are much better. Quite good, in fact. Enough to cause Bada to say that there were probably "multiple origins of life."

Let’s say that life originated around 3.8 billion years ago and then took tens of millions of years to reach full autonomy or, as Wills says, "be on its way." As it did, there would have been massive amounts of decomposed organic compounds—those with "imperfect" characteristics—available to "feed" it. On one hand that’s a lot of feed; on the other hand, that’s a lot of dying, an area which scientists, like doctors, seldom discuss. Why is unclear. Perhaps it’s because decomposition is seldom studied under the biologist’s microscope. Living matter attracts the majority of their scrutiny. But the importance (not to mention the amount) of decomposition to the evolution of life is prodigious.

Consider this oblique angle. Estimates suggest that the structure of DNA was fixed more than 3 billion years ago. This includes the DNA of our common ancestor in the bacterial realm. So what were the chances that deoxyribonucleic acid developed its very particular sequence? In The Fifth Miracle: The Search for the Origin and Meaning of Life (2000), Paul Davies collects several metaphors to try to explain the unlikelihood of life developing on earth as it did. Among them is a quotation from the British astronomer Fred Hoyle who "likened the odds against the spontaneous assembly of life to those for a whirlwind sweeping through a junkyard and producing a fully functioning Boeing 747." The possible combinations of billions and billions of interacting molecules to make DNA are, as British zoologist Richard Dawkins is fond of intoning about evolutionary possibilities in general, unimaginable but not incalculable.

DNA "against all odds" sounds fantasy-headed, like a George Lucas movie. But, despite the relentlessness of earth’s geology, DNA beat the odds. We know from the paleobiochemical record that virtually all organisms—the estimate is greater than 99 percent—have died out. We know that all protobionts have been annihilated by plate tectonics. Hence, the self-maintaining biomolecule that came after the protobiont was, up to that date, the most improbable entity to have gotten that far. And still, no matter which organism got through, there is an abyss between the one that made it and all those others that didn’t, all those molecules that were recycled, all those mutations that dropped off the turnip truck. Such loss is evolution’s stamp. To overproduce the very many so the very few survive.

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Christopher Wills says that perhaps the fiercest of the ongoing arguments among origin-of-life researchers is whether an origin theory can be tested in the lab. This fascinates him because, he says, "Every other science is approachable in the lab, why not the origin." The success of Stanley Miller’s 1953 experiment is precisely what attracted an array of scientists to study life’s onset. By the middle of this century, Wills believes, biochemists will in a series of headline-grabbing experiments create life, and, thereafter, such experiments by high school kids will be common. Wills imagine the biology teacher’s challenger to her students, "‘Let’s see who can be the first in the class to make life.’ I have a hunch it’s going to be far easier than we think." And yet, he stresses, it has to be "ineluctably" proven, so that people will accept the molecular ab ovo view. To create life in the lab will be a momentous occurrence for two reasons: first, because it may permanently alter the creationist view that God is the only author; and second, because replication may be less complicated than we thought since even high school kids will be able to do it.

Wills, of course, is not claiming that the mystery of creation will be solved with such experiments; the exact conditions that gave rise to life on the early earth are neither knowable nor reproducible. So what will the lab-based synthesis of self-replicating organic compounds prove?

According to Loren Eiseley, a naturalist and author of The Immense Journey (1957), not much. A demonstrable origin, for Eiseley, "suffers from the defect of explaining nothing, even if it should prove true. It does not elucidate the nature of life." Eiseley is pushed not so much by the complexity of origin science as he is by "the loneliness of a man who knows he will not live to see the mystery solved, and who, furthermore, has come to believe that it will not be solved when the first humanly synthesized particle begins . . . to multiply itself in some unknown solution." For Eiseley the origin’s incredibly lucky conditions "will never come again." And it’s this never coming again that broods the egg. We—all creatures—are doomed to sit on what he calls "the egg of night."

To illustrate the quandary, Eiseley writes, "My memory holds the past, and yet paradoxically knows, at the same time, that the past is gone and will never come again." Humans may be able to recognize that the irreversibility of their own pasts resonates with the irreversibility of life’s beginning. But, if DNA’s existence coincides almost with that beginning, does DNA hold its past in the same way that an individual’s memory holds its past? Is part of the genetic code of any biomolecule a key for deciphering that biomolecule’s past? Or does the code only give instructions for replication, that is, what will be?

It is possible that DNA has "remembered" its past, that a genetic sequence may contain the origin’s right splash of atmospheric and terrestrial conditions. But that sequence may have mutated through the aeons as well as been buried and re-buried, ad infinitum. The origin of life that may be locked in DNA appears to us like a million Rosetta stones, concealed under a few billion years of planetary evolution.

No doubt a "knowable" origin has been entombed by what Paul Davies calls "the carnage of natural selection." What seems truly irreducible about the first biomolecule is that carnage is not only programmed into its DNA—the overproduction and death of "too many" organisms so that the very few survive—but that carnage has been in motion so long that it has made the origin of that biomolecule more inscrutable than it may be. Carnage also suggests the immense amount of failure that is necessary to create and sustain life. The rate of mutation’s failure to replicate life is many times that of the rate of mutation’s success in continuing life. While the number of species alive today is a few million, the number of extinct species, according to calculations done in 1952 by paleontologist George Gaylord Simpson, is 500,000,000. With such odds, no wonder every species and every bacteria tries every trick in the book to ward off the hangman.

Merrily we mutate. Mercifully we die. Is that it? Mutation and death, carnage and renewal, annihilation and rebirth—ultimately achieving a kind of platitudinal purposelessness? All entities, whether they do or don’t replicate, have to die with or without ascribing themselves a purpose. Life may have no purpose because the "autonomous self-replicating system" that drives the living bestows little more to do, in the grand scheme, than accomplish the next round of autonomous and imperfect self-replication. Is that purposeless? I don’t know. I do know that because I’m drawn to summer’s resplendence out my window, to the feathery top of a Eucalyptus bending in a coastal breeze, I think (and it may only be my code) that the irredeemable fact of our origin means very little.