# The Tangled Tree: A Radical New History of Life

David Quammen

Our understanding of the ‘tree of life’, with powerful implications for human genetics, human health and our own human nature, has recently completely changed.This book is about a new method of telling the story of life on earth – through molecular phylogenetics. It involves a fairly simple method – the reading of the deep history of life by looking at the variation in protein molecules found in living organisms. For instance, we now know that roughly eight per cent of the human genome arrived not through traditional inheritance from directly ancestral forms, but sideways by viral infection.In The Tangled Tree, acclaimed science writer David Quammen chronicles these discoveries through the lives of the researchers who made them – such as Carl Woese, the most important little-known biologist of the twentieth century; Lynn Margulis, the notorious maverick whose wild ideas about ‘mosaic’ creatures proved to be true; and Tsutomu Wantanabe, who discovered that the scourge of antibiotic-resistant bacteria is a direct result of horizontal gene transfer, bringing the deep study of genome histories to bear on a global crisis in public health.Quammen explains how molecular studies of evolution have brought startling recognitions about the tangled tree of life – including where we humans fit into it. Thanks to new technologies, we now have the ability to alter even our genetic composition – through sideways insertions, as nature has long been doing. The Tangled Tree is a brilliant exploration of our transformed understanding of evolution and of life’s history itself.

## Copyright

William Collins

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This eBook first published in Great Britain by William Collins in 2018

Copyright © David Quammen 2018

Jacket design by Jack Smyth

David Quammen asserts the moral right to be identified as the author of this work.

A catalogue record for this book is available from the British Library.

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Source ISBN: 9780008310684

eBook Edition © September 2018 ISBN: 9780008310691

Version: 2018-07-31

## Dedication

To Dennis Hutchinson and David Roe, my attorneys of the soul

Contents

Cover

Title Page

Copyright

Dedication

THREE SURPRISES: An Introduction

PART I: Darwin’s Little Sketch

Chapter 1

Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Chapter 7

Chapter 8

PART II: A Separate Form of Life

Chapter 9

Chapter 10

Chapter 11

Chapter 12

Chapter 13

Chapter 14

Chapter 15

Chapter 16

Chapter 17

Chapter 18

Chapter 19

Chapter 20

Chapter 21

Chapter 22

Chapter 23

Chapter 24

Chapter 25

Chapter 26

Chapter 27

PART III: Mergers and Acquisitions

Chapter 28

Chapter 29

Chapter 30

Chapter 31

Chapter 32

Chapter 33

Chapter 34

Chapter 35

Chapter 36

PART IV: Big Tree

Chapter 37

Chapter 38

Chapter 39

Chapter 40

Chapter 41

Chapter 42

Chapter 43

Chapter 44

Chapter 45

Chapter 46

Chapter 47

Chapter 48

PART V: Infective Heredity

Chapter 49

Chapter 50

Chapter 51

Chapter 52

Chapter 53

Chapter 54

Chapter 55

Chapter 56

Chapter 57

Chapter 58

Chapter 59

PART VI: Topiary

Chapter 60

Chapter 61

Chapter 62

Chapter 63

Chapter 64

Chapter 65

Chapter 66

Chapter 67

Chapter 68

Chapter 69

PART VII: E Pluribus Human

Chapter 70

Chapter 71

Chapter 72

Chapter 73

Chapter 74

Chapter 75

Chapter 76

Chapter 77

Chapter 78

Chapter 79

Chapter 80

Chapter 81

Chapter 82

Chapter 83

Chapter 84

Notes

Bibliography

Illustration Credits

Index

Acknowledgments

About the Book

About the Author

Also by David Quammen

About the Publisher

## THREE SURPRISES. An Introduction

Life in the universe, as far as we know, and no matter how vividly we may imagine otherwise, is a peculiar phenomenon confined to planet Earth. There’s plenty of speculation and probabilistic noodling, but zero evidence, to the contrary. The mathematical odds and chemical circumstances do seem to suggest that life should exist elsewhere. But the reality of such alternate life, if any, is so far unavailable for inspection. It’s a guess, whereas earthly life is fact. Some astounding discovery of extraterrestrial beings, announced tomorrow, or next year, or long after your time and mine, may disprove this impression of Earth’s uniqueness. For now, though, it’s what we have: life is a story that has unfolded here only, on a relatively small sphere of rock in an inconspicuous corner of one middling galaxy. It’s a story that, to the best of our knowledge, has occurred just once.

The shape of this story, in its broad outlines as well as its finer details, is therefore a matter of some interest.

What happened, over the course of roughly four billion years, to bring life from its primordial origins into the fluorescence of diversity and complexity we see now? How did it happen? By what concatenation of accident and determination did it yield creatures so wondrous as humans—and blue whales, and tyrannosaurs, and giant sequoias? We know there have been crucial transitions in evolutionary history, improbable incidents of convergence, dead ends, mass extinctions, big events, and little ones with big consequences—including some fateful contingencies that have left behind evidence of their occurrence embedded subtly throughout the fossil record and the living world. Alter those few contingencies, as a thought experiment, and everything would be different. We wouldn’t exist. Animals and plants wouldn’t exist. Why did it happen as it did, and not some other way? Religions have their responses to such questions, but for science, the answers must be discovered and then supported with empirical evidence, not received in a holy trance.

This book is about a new method of telling that story, a new method of deducing it, and certain unexpected insights that have flowed from the new method. The method has a name: molecular phylogenetics. Wrinkle your nose at that fancy phrase, if you will, and I’ll wrinkle with you, but, in fact, what it means is fairly simple: reading the deep history of life and the patterns of relatedness from the sequence of constituent units in certain long molecules, as those molecules exist today within living creatures. The molecules mainly in question are DNA, RNA, and a few select proteins. The constituent units are nucleotide bases and amino acids—more definition of those to come. The unexpected insights have fundamentally reshaped what we think we know about life’s history and the functional parts of living beings, including ourselves. In particular, there have come three big surprises about who we are—we multicellular animals, more particularly we humans—and what we are, and how life on our planet has evolved.

One of those three surprises involves an anomalous form of creature, a whole category of life, previously unsuspected and now known as the archaea. (Their name gets uppercased when used as a formal taxonomic category: Archaea.) Another is a mode of hereditary change that was also unsuspected, now called horizontal gene transfer. The third is a revelation, or anyway a strong likelihood, about our own deepest ancestry. We ourselves—we humans—probably come from creatures that, as recently as forty years ago, were unknown to exist.

The discovery and identification of the archaea, which had long been mistaken for subgroups of bacteria, revealed that present-day life at the microbial scale is very different from what science had previously depicted, and that the early history of life was very different too. The recognition of horizontal gene transfer (HGT, in the alphabet soup of the experts) as a widespread phenomenon has overturned the traditional certitude that genes flow only vertically, from parents to offspring, and can’t be traded sideways across species boundaries. The latest news on archaea is that all animals, all plants, all fungi, and all other complex creatures composed of cells bearing DNA within nuclei—that list includes us—have descended from these odd, ancient microbes. Maybe. It’s a little like learning, with a jolt, that your great-great-great-grandfather came not from Lithuania but from Mars.

Taken together, these three surprises raise deep new uncertainties—and carry big implications about human identity, human individuality, human health. We are not precisely who we thought we were. We are composite creatures, and our ancestry seems to arise from a dark zone of the living world, a group of creatures about which science, until recent decades, was ignorant. Evolution is trickier, far more intricate, than we had realized. The tree of life is more tangled. Genes don’t move just vertically. They can also pass laterally across species boundaries, across wider gaps, even between different kingdoms of life, and some have come sideways into our own lineage—the primate lineage—from unsuspected, nonprimate sources. It’s the genetic equivalent of a blood transfusion or (different metaphor, preferred by some scientists) an infection that transforms identity. “Infective heredity.” I’ll say more about that in its place.

And meanwhile, speaking of infection: another result of this sideways gene movement involves the global medical challenge of antibiotic-resistant bacteria, a quiet crisis destined to become noisier. Dangerous bugs such as MRSA (methicillin-resistant Staphylococcus aureus, which kills more than eleven thousand people annually in the United States and many more thousands around the world) can abruptly acquire whole kits of drug-resistance genes, from entirely different kinds of bacteria, by horizontal gene transfer. That’s why the problem of multiple-drug-resistant superbugs—unkillable bacteria—has spread around the world so quickly. By such revelations, both practical and profound, we’re suddenly challenged to adjust our basic understandings of who we humans are, what has gone into the making of us, and how the living world works.

This whole radical reset of biological thinking arose from several points of origin in space and time. One among them, maybe the most crucial, deserves mentioning here: the time was autumn 1977; the place was Urbana, Illinois, where a man named Carl Woese sat with his feet on his desk, before a blackboard filled with notes and figures, posed jauntily for a photographer from the New York Times. The accompanying Times story for which the photo was shot, announcing that Woese and his colleagues had discovered “a separate form of life” constituting a “third kingdom” of biological forms in addition to the recognized two, ran on November 3, 1977. It was front page, above the fold, shouldering aside items on the kidnapped heiress Patty Hearst and an arms embargo against the apartheid regime in South Africa. Big news, in other words, whether or not the average Times reader could grasp, from such a lean telling, just what was meant by “a separate form of life.” That article marked the apex of Woese’s fame, his Warhol moment: fifteen minutes of limelight, then back to the lab. Woese brought radical changes—to his own field, to the story of life—and yet he remains unknown to most people outside the rarefied corridors of molecular biology.

Carl Woese was a complicated man—fiercely dedicated and very private—who seized upon deep questions, cobbled together ingenious techniques to pursue those questions, flouted some of the rules of scientific decorum, made enemies, ignored niceties, said what he thought, focused obsessively on his own research program to the exclusion of most other concerns, and turned up at least one or two discoveries that shook the pillars of biological thought. To his close friends, he was an easy, funny guy; caustic but wry, with a love for jazz, a taste for beer and scotch, and an amateurish facility on piano. To his grad students and postdoctoral fellows and laboratory assistants, most of them, he was a good boss and an inspirational mentor, sometimes (but not always) generous, wise, and caring.

As a teacher in the narrower sense—a professor of microbiology at the University of Illinois—he was almost nonexistent as far as undergraduates were concerned. He didn’t stand before large banks of eager, clueless students, patiently explaining the ABCs of bacteria. Lecturing wasn’t his strength, or his interest, and he lacked eloquent forcefulness even when presenting his work at scientific meetings. He didn’t like meetings. He didn’t like travel. He didn’t create a joyous, collegial culture within his lab, hosting seminars and Christmas parties to be captured in group photos, as many senior scientists do. He had his chosen young friends, and some of them remember good times, laughter, beery barbecues at the Woese home, just a short walk from the university campus. But those friends were the select few who, somehow, by charm or by luck, had gotten through his shell.

In later years, as he grew more widely acclaimed, receiving honors of all kinds short of the Nobel Prize, Woese seems also to have grown bitter. He considered himself an outsider. He was elected to the National Academy of Sciences, an august body, but tardily, at age sixty, and the delay annoyed him. He became, by some reports, distant from his family—a wife and two children, seldom mentioned in published accounts of his scientific labors. He was a brilliant crank, and his work triggered a drastic revision of one of the most basic concepts in biology: the idea of the tree of life, the great arboreal image of relatedness and diversification. For that reason, Woese’s moment of triumph in Urbana, on November 3, 1977, has its place near the core of this book.

Other scientists and other discoveries are connected to Woese and his tree. A little-known British physician named Fred Griffith, for instance, in the mid-1920s, while researching pneumonia for the Ministry of Health, noticed an unexpected transformation among bacteria: one strain changing suddenly into another strain, presto, from harmless to deadly virulent. This was important in terms of public health (bacterial pneumonia was in those days a leading cause of death) but also, as even Griffith didn’t realize, a clue to deeper truths in pure science.

The mechanism of Griffith’s perplexing transformation remained obscure until 1944, when a quiet, fastidious researcher named Oswald Avery, at the Rockefeller Institute in New York, identified the substance, the “transforming principle,” that can cause such sudden change from one bacterial identity to another. It was deoxyribonucleic acid. DNA. Less than a decade later, Joshua Lederberg and his colleagues showed that this sort of transformation, relabeled “infective heredity,” is a routine and important process in bacteria—and, as later work would show, not just in bacteria. Meanwhile, the corn geneticist Barbara McClintock, discovering genes that bounce from one point to another on the chromosomes of her favorite plant, worked with very little support or recognition through the prime years of her career—and then accepted a Nobel Prize at age eighty-one.

Lynn Margulis, a Chicago-educated microbiologist unique in almost every way, shared at least one thing with McClintock: the frustrations of being dismissed by some colleagues as an eccentric and obdurate woman. In Margulis’s case, it was for reviving an old idea that had long been considered wacky: endosymbiosis. What she meant by the term was, roughly, the cooperative integration of living creatures within living creatures. That is, not just tiny creatures within the bellies or noses of big creatures, but cells within cells. More specifically, Margulis argued that the cells constituting every creature in the more complex divisions of life—every human, every animal, every plant, every fungus—are chimerical things, assembled with captured bacteria inside nonbacterial receptacles. Those particular bacteria, over vast stretches of time, have become transmogrified into cellular organs. Imagine an oyster, transplanted into a cow, that becomes a functional bovine kidney. This seemed crazy when Margulis proposed it in 1967. But she was right about the matter, mostly.

Fred Sanger, Francis Crick, Linus Pauling, Tsutomu Watanabe, and other scientists played crucial parts in this chain of events too, sometimes by force of personality as well as by scientific brilliance. Slightly deeper in the past lie obscure figures such as Ferdinand Cohn, Edward Hitchcock, and Augustin Augier, as well as more famous ones, including Ernst Haeckel, August Weismann, and Carl Linnaeus. The ghost of Jean-Baptiste Lamarck rises here again to skulk along inescapably in the shadows of evolutionary thinking.

Such people, all contributors to a scientific upheaval, are of additional interest for the ways their works grew from their lives. They serve as good reminders that science itself, however precise and objective, is a human activity. It’s a way of wondering as well as a way of knowing. It’s a process, not a body of facts or laws. Like music, like poetry, like baseball, like grandmaster chess, it’s something gloriously imperfect that people do. The smudgy fingerprints of our humanness are all over it.

Humans aren’t the only important characters in this book. There are also a lot of other living creatures, whose unique histories and foibles illustrate points in the story I’m trying to tell. Many of them are microbes—those bacteria I’ve mentioned, those archaea, and other teeny things. Please don’t be fooled by their smallness; their implications and impacts are big. And don’t be daunted by their names, which are mostly expressed in scientific Latin: Bacillus subtilis and Salmonella typhimurium and Methanobacterium ruminantium and other monstrous tongue twisters. The reason I call them by those names is not because I like arcane language but because no other labels exist. Microbes generally don’t get the courtesy of common names at the species level, casual monikers such as southern giraffe, olive bunting, monarch butterfly, and Komodo dragon. If the bacterium known as Haemophilus influenzae could be accurately called Fleming’s nose-tickler, I promise you I would do it.

One other featured character, of the human sort, should be introduced here. He’s a bearded American microbiologist with a penchant for philosophical musing, tucked away at a university in Nova Scotia. This man has linked Carl Woese, Lynn Margulis, and much of the new work in molecular phylogenetics into a pungent challenge against biology’s central metaphor. His name is Ford Doolittle. He’s tall, diffident in manner though not in thought, and enjoys causing a little intellectual discomfort. At the turn of the millennium, Doolittle published an essay titled “Uprooting the Tree of Life,” which helped release a cascade of arguments. I caught wind of him through that essay and his related writings, notably those in which he discussed horizontal gene transfer and its implications. “Horizontal what?” was my earliest thought. Then I pilgrimed to Halifax and camped for days in his office. Doolittle is semiretired, still guiding graduate students, still well funded with a prestigious research grant, but no longer growing radioactive bacteria in a lab in order to deduce bits of their genomes (the totality of their DNA) from images on chest X-ray films. He’s no longer pulling chopped molecules through electrophoretic gels, as he did in the pioneer days. He reads, he thinks, he writes, he draws. (He takes art photographs, mainly for his own amusement, and occasionally mounts a gallery show, but that’s another realm of enterprise entirely.) In fact, part of what has made Ford Doolittle so influential is that, in addition to his qualifications in biology, he writes far better than most scientists—and he draws deftly, turning big concepts into graceful, cartoony shapes. Doolittle’s father was a painter and an art professor. Young Ford considered an art career himself, though his father called that “a terrible way to make a living.” Then, when he was fifteen years old, in 1957, the Soviets put Sputnik into space, persuading Ford and many other Americans that science and engineering were the more urgent, forceful pursuits. He went to Harvard College and studied biochemistry. The artistic impulse never left him. Nowadays, to illustrate his subversive thinking and his genial provocations, he draws trees that aren’t trees.

Woese, Doolittle, Margulis, Lederberg, Avery, Griffith, and the others—they all have their roles in this story. But a more natural starting point is much earlier: London, 1837, with a very different scientist, in a very different situation.

PART I

## [1]

Beginning in July 1837, Charles Darwin kept a small notebook, which he labeled “B,” devoted to the wildest idea he ever had. It wasn’t just a private thing but a secret thing, a record of his most outrageous thoughts. The notebook was bound in brown leather, with a tab and a clasp; 280 pages of cream-colored paper, compact enough to fit in his jacket pocket. Portable, but no toss-away pad. Its quality of materials and construction reflected the fact that Darwin was an affluent young man, living in London as a naturalist of independent means. He had arrived back in England just nine months earlier from the voyage of HMS Beagle.

That journey, consuming almost five years of Darwin’s life, on sea and land, mostly along the South American coastline and inland to the plains and mountains, though with notable other stops on the roundabout way home, would be the only major travel experience of his sheltered, privileged life. But it was enough. A mind-awakening and transformative opportunity, it had given him some large ideas that he wanted to pursue. It had opened his eyes to an astonishing phenomenon that demanded explanation. In a letter to his biology professor and friend John Stevens Henslow, back at Cambridge University, written from Sydney, Australia, Darwin mentioned his puzzling observations of the mockingbirds (not the finches) of the Galápagos Archipelago, a set of volcanic nubs in mid-Pacific. These gray, long-beaked birds differed from island to island but so subtly that they seemed to have diverged from one stock. Diverged? Three kinds of mockingbird? Varying slightly, this island to that? Yes: they appeared distinct but similar, in a way that suggested relatedness. If that impression were true, Darwin confided to Henslow, confessing an intellectual heresy, “such facts would undermine the stability of species.”

The stability of species represented the bedrock of natural history. It was taken for granted, and important, not just among clergy and pious lay people but scientists too. That all the varied forms of creatures on Earth had been fashioned by God, in special acts of creation, and are therefore immutable, was an article of faith to the Anglican scientific establishment of Darwin’s era. This tenet is known as the special-creation hypothesis, though at the time, it seemed less hypothesis than dogma. It had been embraced and supported by prominent naturalists and philosophers of the scientific culture within which Darwin had been educated at Cambridge. He was now home from his wildcat voyage, a youthful adventure with a bunch of rough English sailors, about which his stern father had been skeptical at the start. The experience had altered him—though not in the ways his father may have feared. He hadn’t become a drunk or a libertine. He didn’t curse like a bosun. Darwin’s wanderlust, satisfied physically, was now intellectual. He intended to investigate, very discreetly, a radical alternative to scientific orthodoxy: that the forms of living creatures weren’t eternally stable, as God had created them, but instead had changed over time, one into another—by some mechanism that Darwin didn’t yet understand.

It was a risky proposition. But he was twenty-seven years old and deeply changed by what he had seen and, in a quiet way, very gutsy.

So he had set himself up in the big city, with lodgings on Great Marlborough Street, a convenient location for his visits to the British Museum. This was just a few doors down from the house where his elder brother, Erasmus, had already settled. Darwin joined scientific clubs, the Geological Society, the Zoological Society, but had no job. Didn’t need one. The same formidable father who had first disapproved of the Beagle voyage—Dr. Robert Darwin, a wealthy physician up in the town of Shrewsbury—was now rather proud of his second son, the young naturalist well regarded within British scientific circles. Grumpy on the outside, generous within, Dr. Darwin had made supportive arrangements for both brothers. And Charles was single. He sauntered around London, he handled follow-up tasks on his specimens from the voyage, he worked on rewriting his Beagle diary into a travel book, and—very privately—he ruminated about that radical alternative to special creation. He read widely, scribbling facts and phrases into various notebooks. The “A” notebook was devoted to geology. The B notebook was first of a series on what, to himself only, he called “transmutation.” You can guess what that meant. Darwin had begun thinking his way toward a theory of evolution.

He opened the B notebook, in July 1837, with a few phrases alluding to a book titled Zoonomia; or the Laws of Organic Life, published decades earlier by his own grandfather, another Erasmus Darwin. Zoonomia was a medical treatise (Erasmus was a physician), but it contained some provocative musings that sounded vaguely evolutionary. All warm-blooded animals “have arisen from one living filament,” according to Zoonomia, and they possess “the faculty of continuing to improve” in ways that could be passed down across the generations, “world without end!” Improvement across generations? Heritable change throughout the history of the world? That was contrary to the special-creation hypothesis, but not too surprising from a gouty, libidinous freethinker and sometime poet such as old Erasmus. Darwin had read Zoonomia during his student days and shown little sign of giving his grandfather’s daring ideas much credit. But now, on revisiting, he took them as a point of departure. Page one, entry one, in the B notebook: his grandfather’s title, Zoonomia, followed by reading notes.

Then again, those wild suggestions didn’t lead anywhere. Erasmus Darwin had offered no material mechanism for “the faculty of continuing to improve,” and a material mechanism was what young Charles wanted, though he may not have fully realized that yet. As reflected in the B notebook, he now went from his grandfather’s work to other readings, other speculations and questions, jotting down clipped phrases, often in bad grammar and punctuation. He wasn’t writing to publish. These were messages to himself.

“Why is life short,” he asked, omitting the question mark in his haste. Why is reproduction so important? Why do animals of a given kind tend to be constant in form across an entire country but to differ at least slightly on separate islands? He remembered the giant tortoises on the Galápagos, where his stopover had lasted only thirty-five days but catalyzed an upheaval in his thinking. He remembered the mockingbirds too. And why had he seen two distinct kinds of “ostriches” (his label for big, flightless birds now known as rheas) on the Argentine Pampas, one living north of the Rio Negro, one south of it? Did creatures somehow become different when isolated? Put a pair of cats on an island, let them breed and inbreed there for generations, with a little pressure from enemies, and “who will dare say what result,” Darwin wrote. He dared. The descendants might come to look different from other cats, might they not? He wanted to understand why.

Another important question: “Each species changes. does it progress.” Do the cats become better cats, or at least better cats for catting on that particular island? If so, how long would it take? How far would it go? What are the logical limits, if “every successive animal is branching upwards” and with “different types of organization improving,” new forms arising, old forms dying out? That one word, branching, was freighted with interesting implications: of directional growth, of divergence, of an arboreal form. And these questions Darwin asked himself, they applied not just to cats and ostriches but also to armadillos and sloths in Argentina, to marsupials in Australia, to those huge Galápagos tortoises, and to the wolflike Falkland Islands fox, all peculiar in certain ways, all unique to their isolated places, but recognizably similar to their correlatives—other cats and tortoises and foxes, etcetera—elsewhere. Darwin had seen a lot. He was an acutely observant and reflective young man. He sensed that he had seen patterns, not just particulars. It almost seemed, he wrote, that there was a “law of adaptation” at work.

All this and more, facts and speculations, crammed into the first twenty-one pages of notebook B. The pages are mostly undated, so we can’t know how many days or weeks passed in the opening burst of effort. Anyway, he didn’t yet have his theory. Big ideas were coming at him like diving owls. He needed some order as much as he needed the jumble of tantalizing clues. Maybe he needed a metaphor. Then, on the bottom of page 21, Darwin wrote: “organized beings represent a tree.”

## [2]

We don’t know whether Darwin sat back after writing that statement and breathed deep with a new sense of clarity, but he might have. And he was entitled.

Then he scribbled on. The tree is “irregularly branched,” he told the B notebook, “some branches far more branched.” Each branch diverges into smaller branches, he wrote, and then twigs, “Hence Genera,” the next higher category above species, which would be the twiglets or terminal buds. Some buds die away without yielding further growth—species extinction, end of a line—while new buds appear, somehow. Although the very idea of extinction had once been problematic among naturalists and philosophers, doubted as a possibility or rejected outright on grounds that God’s acts of special creation couldn’t be undone, Darwin recognized that there’s “nothing stranger in death of species” than in death of an individual. In fact, extinction was not just natural but necessary, making space for new species as old ones die away. He wrote: “The tree of life should perhaps be called the coral of life, base of branches dead,” ancestral forms gone. Darwin knew something about coral, having seen reefs at Keeling Atoll in the eastern Indian Ocean and elsewhere during the Beagle voyage. They fascinated him; he concocted a theory of how reefs are formed; and in 1842, five years after this notebook entry, he would publish a book about coral reefs. Coral seemed apt—branching coral, not brain coral or table coral, was what he had in mind—because the lower limbs and base are lifeless calcitic skeleton, left behind like extinct forms of ancient lineages as the soft polyps advance upward like living species. But even he seems to have sensed that “the coral of life” didn’t have the same memorable ring. He drew a feeble pen sketch, on page 26 in the B notebook, of a three-branched coral of life, with dotted lines depicting the inanimate lower sections. And then he let the coral idea slide, abandoning that metaphor.

The tree of life was better. It was already a venerable notion in 1837, and Darwin could adapt it to his purposes as an evolutionary theorist—easier than inventing a new trope from scratch. Of course, to make that adaptation was to alter its meaning radically. Never mind, he took the step. Ten notebook pages along, he sketched a much livelier and more complex figure in bold strokes, with a trunk rising into four major limbs and several minor ones, each major limb diverging into clusters of branches, one branch within each cluster labeled A, B, C, D. The branches B and C were near neighbors in the treetop, within adjacent clusters, indicating close relationships among the creatures on those branches. The letter A was far away, on the opposite side of the tree’s crown, signaling a more distant relationship—but still a relationship. The letters were placeholders, meant to represent living species, or maybe genera. Felis, Canis, Vulpes, Gorilla. We don’t know exactly what he had in mind, and maybe it was nothing so specific. Anyway, this was a thunderous assertion, abstract but eloquent. You can look at the little sketch today, with its four labeled branches amid the limbs and the crown, and imagine the evolutionary divergence of all life from a common ancestor.


Darwin’s 1837 sketch, redrawn by Patricia J. Wynne.

Just above the sketch, as though gesturing toward it bashfully, Darwin wrote: “I think.”

## [3]

Darwin didn’t invent that phrase, “the tree of life,” nor originate its iconic use, though he put it to new purpose in his theory. Like so many other metaphors embedded deep in our thinking, it came down murkily, modified and reechoed, from early versions in Aristotle and the Bible. (Why do these things always go back to Aristotle? Well, that’s why he’s Aristotle.) In the Bible, it’s a grand bookend motif, invoked in Genesis 3 just as Adam and Eve are booted out of the Garden, and reappearing at the end of Revelation, on the very last page of the King James version—excellent placement for a launch into Western culture. There in Revelation 22, verses 1–2, the authorial prophet describes his ecstatic vision of the “water of life,” flowing out like a pure river from the throne of God, and beside which grows “the tree of life,” bearing fruit every month, plus leaves “for the healing of the nations.” This tree possibly represents Christ, supplying his leafy and fruity blessings to the world; or maybe it’s grace, or the Church. The passage is opaque, and differences in translations (one tree or many?) have confused things further. The point here is simply that the “tree of life” is an ancient poetic image, a resonant phrase, variously construable, with a long presence in Western thought.

In Aristotle’s History of Animals, written during the fourth century BCE, the tree of life is not yet a tree. It’s more like a ladder of nature or—as later Latinized from his Greek—a scala naturae. According to Aristotle, the diversity of the natural world “proceeds” from lifeless things such as earth and fire to living creatures such as animals “little by little,” in a progression so incremental that it’s impossible to draw absolute lines between one form and another. This idea remained useful throughout the Middle Ages and beyond, turning up in woodcuts during the sixteenth century as a Great Chain of Being or a Ladder of Ascent and Descent of the Intellect, which typically rose step-by-step from inanimate substances such as stone or water, to plants and then beasts, then humans, then angels, and finally to God. By that point it was a “Stairway to Heaven,” almost five centuries before Led Zeppelin.

The Swiss naturalist Charles Bonnet reverted to this linear, stair-step model as late as 1745, even while other Enlightenment thinkers and artists were allowing images of nature’s diversity to burgeon sideways with limbs and branches. Bonnet’s treatise on insects, published that year, included a foldout diagram of his “Idea of a Scale of Natural Beings,” arranged in vertical ascent from fire, air, and water, through earth and various minerals, upward to mushrooms, lichens, plants, and then sea anemones, followed by tapeworms and snails and slugs, upward further to fish and then flying fish in particular, and then birds, above which came bats and flying squirrels, then four-legged mammals, monkeys, apes, and lastly man. See the logic? Flying fish are superior to other fish because they fly; bats and squirrels exist on a higher level than birds because bats and squirrels are mammals; orangutans and humans are the best of mammals, and humans are more best than anybody. Bonnet made his living as a lawyer but much preferred studying insects and plants. He was a lifelong citizen of the Republic of Geneva, his French ancestors having been chased out of France by religious persecution, and so maybe it’s no accident that his ladder diagram culminated in people, not God.

The other notable absence from Bonnet’s scale of natural beings, besides God, are microbes. He paid no attention to microorganisms, although the pioneering Dutch microscopist Antoni van Leeuwenhoek had discovered the existence of bacteria, protozoans, and other tiny “animalcules” about seventy years earlier. We all know Leeuwenhoek’s name from our reading in high school of Paul de Kruif’s Microbe Hunters (a terrible book full of concocted dialogue and bogus detail, but an influential doorway to the subject) or other storybook histories of science, though we might not remember that Leeuwenhoek was a draper in Delft who started making his own magnifying lenses in order to better inspect the thread-count of textiles. Then he turned the lenses onto other materials, out of sheer curiosity, and made astonishing discoveries: he found menageries of tiny creatures living in lake water, in rain water, in water from drain pipes, even in scrapings of crud from his own teeth.

Leeuwenhoek’s revelatory observations of microbial life were reported in the journal of the Royal Society of London and became famous in scientific circles throughout Europe, but Charles Bonnet wasn’t interested enough in those “very wee animals” to fit them into his rising scale—not even where they might dismissively have been slotted, somewhere between asbestos and truffles. That omission presages a lasting discomfort with placing microbes on the ladder of life or, harder still, arranging their diverse forms on the tree—and it’s a discomfort to which I’ll return, because it became acute in 1977.

The linear approach to depicting life’s diversity was on the way out, notwithstanding Charles Bonnet’s scale of nature, and being replaced by its more complicated and dimensional successor, the tree. By the late eighteenth century and the start of the nineteenth, natural philosophers (we’d call them scientists, but that word didn’t yet exist) tried to classify and arrange living creatures into distinct groups and subgroups, reflecting their similarities and differences and some sort of organizing schema. The linear alignment, in order of what passed for increasing sublimity, the ladder raised toward God, was no longer satisfactory. There had been a knowledge explosion in Europe since the great age of sailing explorations began—knowledge of diverse animals, plants, and other creatures from all over the world—and scholars wanted to set that explosive abundance of new facts within hierarchical categories so that it could be easily accessed and used.

This wasn’t evolutionary thinking; it was just data management. The knowledge would fill volumes (one man alone, the German naturalist Alexander von Humboldt, published a thirty-volume account of his travels in South America), making all the more necessary an overview, an organizing principle, that could be apprehended at a glance: an illustration. But the illustrators now needed two dimensions, not one, and so the ladder turned into a trunk, and the trunk sprouted limbs, and the limbs diverged into branches. This offered more scope, sideways as well as up and down, for arranging the varied abundance of known creatures.

The tree of life was an old symbol by then, an old phrase, dating back at least to those mentions in Genesis and Revelation. The tree had also served as a model for family histories—the genealogical tree or pedigree of a German duke, for instance. Now the secularized tree became useful for organizing biology. Among the first to embrace this convention was another Frenchman, Augustin Augier, who wrote in 1801 that “a figure like a genealogical tree appears to be the most proper to grasp the order and gradation” of what concerned Augier: the diversity of plants.

Augier was an obscure citizen of the French Republic, living in Lyon, working on botany part-time; his real profession was unknown, his biographical details lost, even to a historian of Lyonnais botanists writing a hundred years later. Augier disappeared. But he left behind a book, a little octavo volume, in which he proposed a new classification of plants, “according to the order that Nature appears to have followed.” That is, a “natural order,” as opposed to an artificial classification system based merely on human whim or convenience. And in the book was a figure representing that system: his arbre botanique (botanical tree). Its trunk and limbs look almost as orderly and stiff as a menorah, but its sideways branching and copious leafing suggest a rife multiplicity of plant forms.

Again, this didn’t imply any heretical ideas about origins. Augier was no evolutionist before his time. His natural order wasn’t meant to suggest that all plants had descended from common ancestors by some sort of material process of transformation. God was their maker, shaping the varied forms individually: “It appears, and one can hardly doubt it, that the Creator, when making flowers, followed certain proportions and progressions in the number of their different parts.” Augier’s contribution, as he saw it, was discovering those proportions and progressions—design principles that had satisfied the Deity’s neat sense of pattern—and using them after the fact to organize botanical knowledge into a tidy system.

Augier wasn’t the first naturalist to hanker for a natural order of nature’s diversity. Aristotle had classified animals as “bloodless” and “blooded.” In the first century of our era a Greek physician named Dioscorides, attached to the Roman army, gathered lore on more than five hundred kinds of plants, arranging them in a compendium mainly on the basis of their medicinal, edible, and perfumatory uses. That book, in various reprints and translations, served as a trusted botany text for the next fifteen hundred years. Toward the end of its run, around the time of the Renaissance, as people traveled more widely and paid closer attention to the empirical details of nature, old Dioscorides gave way to newer illustrated herbals. These were essentially field guides to botany, graced with better illustrations based on improvements in drawing and woodcut techniques, but still organized for convenience of use, not natural order. In the sixteenth century, Leonhart Fuchs produced one of those books, an herbal cataloging hundreds of plants, beautifully illustrated and arranged in alphabetical order. Two centuries later, the great systematizer Carl Linnaeus described a genus of plants with purplish red flowers, naming it Fuchsia in honor of Leonhart Fuchs (and hence we got also the color, fuchsia). Linnaeus himself, a Swede who traveled widely as a young man and then took up a professorial life in Uppsala, emerged from this herbalist tradition but went beyond it.


Augier’s Arbre Botanique, 1801.

Linnaeus’s Systema Naturae, as first published in 1735, was a unique and peculiar thing: a big folio volume of barely more than a dozen pages, like a coffee-table atlas, in which he outlined a classification system for all the members of what he considered the three kingdoms of nature: plants, animals, and minerals. Notwithstanding the inclusion of minerals, what matters to us is how Linnaeus viewed the kingdoms of life.

His treatment of animals, presented on one double-page spread, was organized into six columns, each topped with a name for one of his classes: Quadrupedia, Aves, Amphibia, Pisces, Insecta, Vermes. Quadrupedia was divided into several four-limbed orders, including Anthropomorpha (mainly primates), Ferae (doggish forms such as wolves and foxes, plus cat forms such as lions and leopards, in addition to bears), and others. His Amphibia encompassed reptiles as well as amphibians, and his Vermes was a catchall group containing not just worms, leeches, and flukes but also slugs, sea cucumbers, starfish, barnacles, and other sea animals. He divided each order further into genera (with some recognizable names such as Leo, Ursus, Hippopotamus, and Homo), and each genus into species. Apart from the six classes, Linnaeus also gave a half column to what he called Paradoxa: a wild-card assemblage of mythic chimeras and befuddling but real creatures, including the unicorn, the satyr, the phoenix, the dragon, and a certain giant tadpole (Pseudis paradoxa, under its modern label) that, strangely, paradoxically, shrinks during metamorphosis into a much smaller frog. Across the top of the chart ran large letters: CAROLI LINNAEI REGNUM ANIMALE. His animal kingdom. It was a provisional effort, grand in scope, integrated, but not especially original, to make sense of faunal diversity based on what was known and believed at the time. Then again, animals weren’t Linnaeus’s specialty.

Plants were. His classification of the vegetable kingdom was more innovative, more comprehensive, and more orderly. It became known as the “sexual system” because he recognized that flowers are sexual structures, and he used their male and female organs—their stamens and pistils, those delicate little stems sticking up to present and receive pollen—for characterizing his groups. Linnaeus defined twenty-three classes, into which he placed all the flowering plants, based on the number, size, and arrangement of their stamens. Then he broke each class into orders, based on their pistils. To the classes, he gave names such as Monandria, Diandria, and Triandria (one husband, two husbands, three husbands), and, within each class, ordinal names such as Monogynia, Digynia, and Tryginia (numbers of wives, yes, you get the idea), thereby evoking all sorts of polygamous and polyandrous ménages that must have caused lewd smirks and disapproving scowls among his contemporaries. A plant of the Monogynia order within the Tetrandria class, for instance: one wife with four husbands. Linnaeus himself seems to have enjoyed the sexy subtext. And it didn’t prevent his botanical schema from becoming the accepted system of plant classification throughout Europe.

Our man Augustin Augier, coming along a half century later with his botanical tree of classification, seems to have seen himself challenging Linnaeus’s overly neat sexual system. “Stamen number is a striking character,” Augier conceded, but “not when it comes to the examination of plants”—that is, not always unambiguous and therefore not reliable as a basis for organizing the great jumble of botanical life. He nodded respectfully to Linnaeus—also to the French botanist Joseph Pitton de Tournefort, who had sorted plants into roughly seven hundred genera based on their flowers, their fruits, and other bits of their anatomy—and offered his own system, using multiple characters for different levels of sorting and to resolve the ambiguities and fine gradations. “This figure, which I call a botanical tree, shows the agreements which the different series of plants maintain amongst each other, although detaching themselves from the trunk; just as a genealogical tree shows the order in which different branches of the same family came from the stem to which they owe their origin.” All discrete, yet all connected: bits of the same tree.

But they weren’t connected, in Augier’s mind, by descent from shared ancestors. Despite the hint he gave to himself in his language about family trees—all branches divergent from “the stem to which they owe their origin”—there is no evidence in Augier’s writing or his tree figure that he had embraced, or even imagined, the idea of evolution.

## [4]

That idea was coming soon, and, with its arrival, the tree of life would change meaning. The change was drastic, soul shaking to many people who lived through it, because it reflected a challenge to faith, and it met strong resistance. Jean-Baptiste Lamarck, France’s great early evolutionist, and Edward Hitchcock, an American who prided himself a “Christian geologist,” are the two scientists whose works—and whose graphic illustrations—best reflect how tree thinking shifted during the decades before Darwin unveiled his theory of evolution.

Lamarck was a protean figure: a soldier from a family of soldiering minor nobility who transformed himself into a botanist, then into a professor of zoology at the Muséum National d’Histoire Naturelle in Paris, to which he was appointed in 1793, on the eve of the Reign of Terror. His title at the museum put him in charge “of insects, of worms, and microscopic animals,” three categories of life he had never studied, but he adapted fast, and even invented the word invertebrates to cover them. He abandoned plants and studied his invertebrates through the grimmest days of the French Revolution, earning a measly salary but at least keeping his head, as other scientists such as Antoine-Laurent Lavoisier went to the guillotine. Lamarck had probably helped his standing among the revolutionaries back in 1790 while employed at what was then the Jardin du Roi, when he urged dropping the royal label and renaming that institution the Jardin des Plantes. Clearly, he had good political instincts. He held the conventional view of species—that they were fixed forever and created by God—until 1797, but then his views changed, possibly as a result of his study of fossil and living mollusks, which seemed to show patterns of gradual transformation. He came out as an evolutionist on May 11, 1800, in his first lecture for the year’s course on invertebrates. After that, he published three major works on evolutionary zoology, the most influential being his Philosophie Zoologique in 1809.

Lamarck outlived four wives and three of his seven children, living beyond the revolution, through the Napoleonic era and most of the Bourbon Restoration, a handsome man with a downturned mouth, balding slowly across his pate, blind for his final ten years, his faithful daughter, Cornelie, giving her life to him and reading him French novels. He died at eighty-five and was eulogized by important colleagues such as Geoffroy St. Hilaire, after which things didn’t go so well: his remains were interred at the Montparnasse Cemetery in a common trench, not a permanent individual plot, and because such burial trenches were regularly recycled, his bones may have ended up in the Paris catacombs, along with those of thousands of paupers and other neglected folk. There was no Lamarck grave to visit. He became, according to one biographer, rather quickly “forgotten and unknown.” His fame would return, if not immediately, but still it was a cold finish for the world’s first serious evolutionary theorist.

Lamarck nowadays is commonly associated with what his name came to represent: Lamarckism, an easy but imprecise label for the idea of the inheritance of acquired characteristics. Many people are vaguely aware of him as a predecessor to Darwin; he is seen as a forerunner whose theory was provocative but wrong, refuted by later evidence because it depended, as Darwin’s did not, on that illusory notion of acquired traits being heritable. (The real facts aren’t so simple. For instance, Darwin himself included the inheritance of acquired characteristics as a force in evolution, under the label “use and disuse.”) The most familiar example of such inherited adjustments, which Lamarck himself offered, is the giraffe. The proto-giraffe on the dry plains of Africa stretches to reach high foliage, its neck lengthens (supposedly) from the effort, its front legs lengthen too, and therefore (again supposedly) its offspring are born with longer necks and front legs. Lamarckism, in that cartoonish form, has been easy to despise but harder to kill off entirely.

It came back into fashion during the late nineteenth century, when the general idea of evolution gained acceptance but the crucial details of Darwin’s particular theory, offering natural selection as the primary mechanism, were widely rejected. Natural selection just seemed too mechanistic, too stark and unguided, and many evolutionists found it unpalatable. This situation went on for decades—the world accepting Darwin’s idea of evolution but not his explanation of how it occurs—though only historians remember that now. Lamarckism became neo-Lamarckism and seemed a less nihilistic alternative. It has continued to linger as a dubious but ineradicable notion—embodied in that single tenet, the inheritance of acquired characteristics—enjoying small surges of reconsideration even down to the present day.

But that single tenet was never Lamarck in totality. He had other ideas, some even worse. He believed in spontaneous generation. He disbelieved in extinction, at least as a natural process. He argued that “subtle fluids,” surging through the bodies of living creatures, helped reshape them adaptively.

In one of his earlier botanical works, before the shift to animals and the epiphany about evolution, Lamarck had arranged plants in what he called “the true order of gradation”: from least perfect and complete to most, ascending along an old-fashioned ladder of life. He matched that with a separate ladder for animals, a “counterpart” arrangement, showing an ascending series of forms: from worms, through insects, through fish and amphibians and birds, to mammals. Neither of those ladders hinted at divergence from common ancestors or transformation. But in the 1809 book Philosophie Zoologique, he included a different sort of figure, subtle yet dramatic, depicting animal diversity. It was a branched diagram, descending down the page, with major animal groups connected by dotted lines, like one of those connect-the-dots games for kids on the paper placemats at a pancake house. Connect the dots and discover that the secret shape is … an airplane! Or … an elephant! Or … George Washington’s head! In Lamarck’s dotted figure, the secret shape was a tree.


Lamarck’s tree of dots, 1809.

Birds sat perched on a branch divergent from reptiles. Insects had diverged from the main trunk before it yielded mollusks. Walruses and other marine mammals lay farther along that trunk, beyond which still other branches led to whales, then to hoofed mammals, and finally to all other mammals. Wrong though it was about the particulars, and despite being upside down, this figure marked an important transition in scientific thought. Scholars tell us that it was the earliest evolutionary tree.

## [5]

Edward Hitchcock stands as a counterpoint to Lamarck, with that first evolutionary tree, in that Hitchcock offered a last pre-evolutionary tree in the decades before Darwin changed everything. In fact, Hitchcock presented two separate trees of life, one for animals, one for plants, in his 1840 book Elementary Geology, which became a successful and often-reprinted text in the mid-nineteenth century. Hitchcock’s trees were also innovative—among the first based on deep knowledge of fossils, not just close observation of living creatures. He called his illustration a “Paleontological Chart,” and what it shows is diversification of the animal and plant kingdoms charted against geological time, from the Cambrian period (beginning about 540 million years ago) to the present.

Hitchcock’s trees weren’t classically tree shaped, spreading outward into a canopy like a maple or an oak. Each of the two, the one for animals and the one for plants, looks more like a windbreak of tightly placed Lombardy poplars grown to maturity along a roadway. The base of each windbreak is a thick, solid trunk from which rise slender stems, fluffy with foliage but without much branching as they ascend. Vertical, parallel, they seem independent: crustaceans, worms, bivalves, vertebrates. The vertebrate stem does branch into several shafts. The shaft leading up to modern mammals culminates in the word Man, atop which sits a regal crown adorned by a cross.

The crowned “Man,” with its cross, tells us what we need to know about Hitchcock’s sense of hierarchy in the living world. He grounded his geology firmly within the tradition known as natural theology, meaning science purposed to illuminate the power and wisdom of God as creator of all, with humans as the culmination of that divine creativity. He was a devout, driven New England Yankee, and his “Paleontological Chart” reflected his view of humans as the apogee of creation, as well as his findings in geology.

Hitchcock was born to a poor family in Deerfield, Massachusetts, his father a Revolutionary War veteran and a hatter by trade, with debts and three sons, who found just enough money to see his boys through primary school and some time at the local academy. After that, as Hitchcock recalled, “nothing was before me but a life of manual labor.” He balked at the idea of apprenticing as a hatter, to his father, or in any other trade. Instead he worked on a farm—it was rented land, cropped by one of his brothers—for a period that stretched on so long, or what felt like so long, that later he claimed not to remember how many years. With his free time, especially rainy days and evenings, young Edward studied science and the classics. Ambitious and hungry, he thought he was preparing himself for Harvard. Under the influence of an uncle, he took up astronomy. Then came the great comet of 1811, a celestial passerby that reached its peak of brightness in the north sky during autumn that year, when Hitchcock was eighteen. He borrowed some instruments from Deerfield Academy and spent night after night measuring its progress. “I gave myself to this labor so assiduously that my health failed,” he wrote later.

The health crisis brought on a religious conversion: from Unitarianism, into which he had drifted, back to the Congregationalism of his father. That passed for a drastic rethink in Edward Hitchcock’s life. In lieu of Harvard, he returned to Deerfield and somehow got hired, at age twenty-three, as principal of the academy. Then he studied for the ministry, was ordained, and became pastor of a Congregationalist church in Conway, Massachusetts, just up the road from Deerfield. Throughout these years and for the rest of his life, Hitchcock remained an invalid in self-image if not bodily, obsessed with his own fragility, continually complaining that he felt death nearby, although he lived to be seventy. One scholar, having looked into his life and work, called him “a hypochondriac of the first rank.”


Hitchcock’s “Paleontological Chart,” 1857 version.

Conveniently for his scientific career, he was “dismissed” from the Conway pastorate in autumn 1825 on the grounds of impaired health and imminent death if (according to his own worried judgment) he didn’t stop preaching, circuiting the parish, and running revivals. Amherst College, recently founded, hired him to teach chemistry and natural history, and he stayed there the rest of his life, serving later as professor of natural theology and geology, and for one nine-year stretch also as president. The early years of Hitchcock’s career at Amherst spanned the period when Charles Lyell, in England, published his multivolume Principles of Geology, a radical work that challenged Scripture-based interpretations of the geological record, including Hitchcock’s own.

The conventional school of thought, known as catastrophism, saw Earth’s history as a series of cataclysmic upheavals cast down like thunderbolts by the Creator, such as the bolt that brought forty days and forty nights of rain, documented in Genesis as Noah’s flood. These catastrophes were considered directional and purposeful, in the sense that God used them as occasions for purging the planet of some creatures (dinosaurs, begone) and adding new creations (mammals, arise). Lyell’s alternative view was uniformitarianism, insisting that the processes and events that shaped Earth in the past were physical, such as erosion and deposition, as well as the occasional volcanic eruption—things that continue to occur in the present at roughly the same rate they did in the past. Those forces caused extinctions, among other effects. Second thoughts by God about what fauna and flora should exist, according to Lyell, did not enter into it.

Hitchcock read Lyell’s work promptly as the first three volumes came out, from 1830 to 1833, and found it all discomforting. He was no young-earth creationist himself; he acknowledged that volcanism and erosion were continuing processes. But he worried that Lyell’s view of the planet would “exclude a Deity from its creation and government.” In an article on deluges, comparing the biblical with the geological records, Hitchcock wrote cattily: “We know nothing of Mr. Lyell’s religious creed. But there is something in such an ambiguous mode of treating of scriptural subjects that reminds us of infidel cunning and duplicity.” Lyell was a dutiful Anglican, not an infidel, at least when he authored Principles of Geology, but Hitchcock seems to have sensed, maybe better than Lyell himself, that his work would nudge some readers toward godless, materialistic ideas.

One of those so nudged was Charles Darwin, who read Lyell’s three volumes aboard the Beagle and followed their influence, not just toward uniformitarianism in geology but eventually (because Lyell described Lamarck’s ideas, without endorsing them) toward a theory of evolution. So although Hitchcock was wrong about Lyell’s supposed “cunning and duplicity,” he was right about Principles of Geology taking readers—one crucial reader, anyway—onto a slippery slope.

In 1840, seven years after Lyell’s third volume appeared, Hitchcock published his own Elementary Geology, and with it that Paleontological Chart of Lombardy poplars, included as a hand-colored, foldout figure presenting his two nonevolutionary trees of life. The chart showed changes in Earth’s flora and fauna over geological time, with this or that group of plants or animals waxing or waning in diversity and abundance, but not much branching of one from another. The cause of those changes, Hitchcock explained in his text, was God’s direct agency, adding and subtracting creatures, improving and perfecting the world as a long-term project. The major groups were present all along, according to this slightly tortured schema, but new species manifesting “a higher organization” had been inserted along the way, until at last Earth was ready for “more perfect” kinds of creatures, “the most generally perfect of all with man at their head.” The gradual introduction of “higher races,” he wrote, “is perfectly explained by the changing condition of the earth which being adapted for more perfect races Divine Wisdom introduced them.” These were special creations by the Deity, appropriate as environments changed. God wasn’t rethinking the planet’s fauna and flora, just adjusting them to newly available niches. If that doesn’t quite make sense, don’t blame Charles Lyell or me.

Hitchcock’s Elementary Geology was a hit. Between 1840 and the late 1850s, it went through thirty editions, to which he made minor revisions of language and data. Throughout all those editions, the trees figure remained—unchanged except for color adjustments. Then something happened. As a consequence of that something, or else by improbable coincidence, the thirty-first edition of Hitchcock’s book, in 1860, contained a notable difference. An omission. No trees.

What happened was that in 1859 Charles Darwin published On the Origin of Species. His book also contained a tree, but one with dangerous new meaning.

## [6]

By that point, Darwin had incubated his theory in secret for half a lifetime. After sketching his little tree into the B notebook in 1837, he had continued reading, gathering facts, pondering patterns, trying out phrases, brainstorming fervidly for another sixteen months in a series of such notebooks, labeled “C” and “D” and “E,” like a man pushing puzzle pieces around on a table. Then suddenly, in November 1838, as recorded in the E notebook, he solved the puzzle of how species must evolve. Combining three pieces in his mind, he hit upon an explanatory mechanism for evolution.

The first piece was hereditary continuity. Offspring tend to resemble their parents and grandparents, providing a stable background of similarity throughout time. The second factor, a countertrend to the first, was that variation does occur. Offspring don’t precisely resemble their parents. Brown eyes, blue eyes, taller, shorter, differences of hair color or nose shape among humans; wing markings in a butterfly, beak size in a bird, length of neck in a giraffe. Reproduction is inexact. Likewise, siblings, as well as parents and offspring, differ from one another. Darwin saw that these two pieces, heredity and variation, stand together in some sort of dynamic tension.

The third puzzle piece, which he had begun considering just recently, having been alerted to it by his eclectic reading, was that population growth always tends to outrun the available means of subsistence. Earth is always getting too full of life. One female cat may give birth to five kittens; one rabbit may deliver eight bunnies; one salmon may lay a thousand eggs. If all those offspring were to survive, and reproduce in their turns, there would soon be a very great lot of cats and bunnies and salmon. Whatever the litter size, whatever the lifetime fecundity, whatever the kind of organism, including humans, we all tend to multiply by geometric progression, not just by arithmetic increase—that is, more like 2, 4, 8, 16 than like 2, 3, 4, 5. Meanwhile, living space and food supply don’t increase nearly so quickly, if at all. Habitat doesn’t replicate itself. Places get crowded. Creatures go hungry. They struggle. The result is competition and deprivation and misery, winners and losers, unsuccessful efforts to breed and, for the less fortunate individuals, early death. Many are called, but few are chosen. The book that awakened Darwin to this reality was An Essay on the Principle of Population, by a severely logical clergyman and scholar named Thomas Malthus.

Malthus’s gloomy treatise was first published in 1798. It went through six editions in the next three decades and influenced British policy on welfare. (It argued against the relatively easy charity of the contemporary Poor Laws, which were soon changed.) Darwin read it in early autumn 1838–“for amusement,” as he recalled later. Seldom is amusement more productive. He came away with the population piece, combined that with his two other pieces, and scribbled an entry in his D notebook about “the warring of the species as inference from Malthus.” Yes, this “warring” applied not just to humans, Darwin realized, but also to other creatures. Competition was fierce, and opportunities were finite. “One may say there is a force like a hundred thousand wedges,” Darwin wrote, all trying to “force every kind of adapted structure” into the gaps in the economy of nature. “The final cause of all this wedgings,” he added, “must be to sort out proper structure & adapt it to change.” By “final cause,” he essentially meant final result: the struggle yielded well-adapted forms. That was the essence, though still inchoate and crudely stated.

Darwin seemed to leave Malthus behind as he finished the D notebook, but returned to him soon in the next. That one, labeled E, begun in October 1838, was bound in rust-brown leather, with a metal clasp. It’s one of the true relics in the history of biology. In its earlier pages, Darwin ruminated further about “the grand crush of population” and alluded repeatedly to what he now called “my theory.” He was growing more confident and clear. Then, on or soon after November 27, with his usual clipped grammar and eccentric punctuation, he wrote:

Three principles, will account for all

> 1 Grandchildren, like, grandfathers

> 2 Tendency to small change … especially with physical change

> 3 Great fertility in proportion to support of parents

Inheritance, variation, overpopulation. He saw how they fit. Put those three together and turn the crank: you’ll get differential survival, based on something or other. Based on what? Based on which variations turn out to be most advantageous. And those variations will tend to be inherited. The result will be gradual transmutation of heritable forms, and adaptation to circumstances, by a process of selective culling. Eventually he gave the crank a name: natural selection.

Twenty years passed after the E notebook entry. The world heard nothing about natural selection.

## [7]

It was a perplexingly long delay, almost two decades, between the writing of those four lines in his secret E notebook and the first public announcement of Darwin’s theory. Longer still, twenty-one years, to publication of the theory in book form—On the Origin of Species appeared in November 1859. The reasons for that delay, which were both scientific and personal, both anxious and tactical, have been minutely examined in other works (including some of mine). We can skip over them here except to note that, when Darwin finally went public with his theory, it was because a younger naturalist had forced his hand by coming forward with the same idea.

Alfred Russel Wallace, after four years of fieldwork in the Amazon and four more in the Malay Archipelago, had hit upon the notion of natural selection (framed in his own language, not that pair of words) and written it up in a short paper. As recounted by Wallace long afterward, the idea came during a layover in his collecting travels through the northern Moluccas. He suffered a bout of fever (maybe malarial), and, amidst it, he had this extraordinary insight. Variation plus overpopulation, minus the unsuccessful variants, would yield heritable adaptation. When the fever broke, and the sweat dried, and the dreamy brainstorm still seemed cogent, Wallace composed his manuscript and then tried to get it considered.

But he was a poor man’s son, working his way through the tropics by selling decorative specimens—bird skins, butterflies, pretty beetles—not a gentleman traveler as Darwin had been on the Beagle. Wallace wasn’t well educated or well connected. He knew almost nobody in the higher circles of British or European science, and almost nobody in those circles knew him—not face-to-face and not as a peer, anyway. He was a collector of dried creatures for pay, a natural-history tradesman. There was class stratification in science as in every other part of Victorian British society. But he had published a few earlier papers in a respectable journal, and one of those papers had drawn favorable attention from Charles Lyell, the great geologist. Oh, and Wallace knew one other famous man, not personally but as a sort of pen pal, who had spoken generously to him in a letter: Charles Darwin.

It was now February 1858. Hardly anyone at that point recognized Darwin for what he was—an evolutionary theorist, in secret—and though Lyell was among that small group who did, as a close friend and confidant, Alfred Wallace certainly wasn’t. Charles Darwin to him was just a conventionally eminent naturalist, author of the Beagle chronicle and other safe books, including several on the taxonomy of barnacles. But a Dutch mail boat would soon stop at the port of Ternate, in the Moluccas, where Wallace had fetched up. He was excited by his own discovery, if it was a discovery, and eager to share this dangerous hypothesis with the scientific world. So he packed up his paper with a cover letter and mailed the packet to Mr. Darwin, hoping that Darwin might find it worthy. If so, maybe Darwin would share it with Mr. Lyell, who might help get it published.

The packet reached Darwin, probably on June 18, 1858, and hit him like a galloping ox. He felt crushed, scooped, ruined—but also honor-bound to grant Wallace’s request, passing the paper on toward publication. It would mean, Darwin knew, letting the younger man take all the credit for this epochal idea he himself had incubated for twenty years but was not yet quite ready to publish. Despite that, he did send the Wallace paper along to Lyell—communicating yelps of his own anguish along with it. Lyell took not just the paper but also the hint. Along with another of Darwin’s close scientific allies, the botanist Joseph Hooker, Lyell talked Darwin back from despair, suggested a posture of sensible fairness rather than self-abnegating honor, and brokered a compromise of shared credit. The result was a clumsily conjoined presentation—a pastiche of Wallace’s paper plus excerpts from Darwin’s unpublished writings—before a British scientific club, the Linnean Society, in the summer of 1858. Lyell and Hooker offered an introductory note, and then simply watched and listened. Proxies read the works aloud, with neither of the authors present. (Darwin was at home, where his youngest son had just died of scarlet fever; Wallace was still out in the far boonies of the Malay Archipelago.) This joint presentation made almost no impression on anyone, not even the few dozen Linnean members in attendance, because the night was hot, the language was obscure, the logic was elliptical, and the big meaning didn’t jump forth.

Seventeen months later, Darwin published On the Origin of Species. That 1859 book, not the 1858 paper or excerpts, launched the Darwinian revolution. It was only an abridged and hasty abstract of the much longer (and more tedious) book on natural selection that Darwin had been writing for years, but The Origin was just enough, in the right form, at the right time. It presented the theory as “one long argument,” not just a bare syllogism, and with oodles of data but not many footnotes. It was plainspoken, and readable by any literate person. It became a bestseller and went into multiple editions. It converted a generation of scientists to the idea of evolution (though not to natural selection as the prime mechanism). It was translated and embraced in other countries, especially Germany. That’s why Darwin is still history’s most venerated biologist and Alfred Russel Wallace is a cherished underdog, famous for being eclipsed, to the relatively small subset of people who have heard of him.

The crux of the “one long argument” comes in chapter 4 of The Origin, titled “Natural Selection,” in which Darwin describes the central mechanism of his theory. It’s the same combination of three principles that he had scratched into his notebook two decades earlier, plus the turned crank. “Natural selection,” he wrote in the book, “leads to divergence of character and to much extinction of the less improved and intermediate forms of life.” Lineages change over time, he stated. You could see that in the fossil record. Different creatures adapt to different niches, different ways of life, and thereby diversify into distinct forms and behaviors. Transitional stages disappear. Then he wrote: “The affinities of all the beings of the same class have sometimes been represented by a great tree. I believe this simile largely speaks the truth.”

## [8]

Darwin explored the tree simile in one extended paragraph, ending that chapter of The Origin. “The green and budding twigs may represent existing species,” he wrote. From there he worked backward: woody twigs and small branches as recently extinct forms; competition between branches for space and for light; big limbs dividing into branches, then those into lesser branches; all ascending and spreading from a single great trunk. “As buds give rise by growth to fresh buds,” Darwin wrote, and those buds grow to be twigs, and those twigs grow to be branches, some vigorous, some feeble, some thriving, some dying, “so by generation I believe it has been with the great Tree of Life, which fills with its dead and broken branches the crust of the earth, and covers the surface with its ever branching and beautiful ramifications.” There’s a nice word: ramifications.

It’s especially good in this context because, while the literal definition is “a structure formed of branches,” from the Latin ramus, of course the looser definition is “implications.” Darwin’s tree certainly had implications.

Furthermore his book, like Edward Hitchcock’s, included a treelike illustration. This was the only illustration, the only graphic image of any sort, in the first edition of The Origin. It appeared between pages 116 and 117, amid his discussion of how lineages diverge over time. A foldout, again like Hitchcock’s, but published in simple black and white. It was a schematic figure, not an artfully drawn tree, not even so lively as the little sketch in his notebook long ago. Darwin called it a diagram. It showed hypothetical lineages, proceeding upward through evolutionary time and diverging—that is, dotted lines, rising vertically and branching laterally. Darwin was no artist, but, even lacking such talent, he could have laid out this diagram with a pencil and a ruler. In its draft version, as sent to the lithographer, he probably had. But it made the arboreal point.

Each increment of vertical distance on the ruled page, Darwin explained, stood for a thousand generations of inheritance. Deep time. Eleven major lineages began the ascent. Eight of those came to dead ends—meaning, they went extinct. Trilobites, ammonites, ichthyosaurs, and plesiosaurs had all suffered such ends, leaving no descendants of any sort. One lineage rose through the eons without splitting, without tilting, like a beanstalk—meaning that it persisted through time, unchanged. That’s much the way horseshoe crabs, sometimes called living fossils, have survived relatively unchanged (at least externally, so far as fossilization can show) over 450 million years. The other two lineages, dominating the diagram, branched often and spread horizontally—as well as climbed vertically. Their branching and horizontal spread represented the exploration of different niches by newly evolved forms. So there it all was: evolution and the origins of diversity.


Darwin’s diagram of divergence, from On the Origin of Species, 1859.

Back in Massachusetts, Edward Hitchcock read Darwin’s book, and it stuck in his craw. This wasn’t his first exposure to the idea of transmutation (he knew of Lamarck’s work and some other wild speculations), but it was the latest statement of that idea, the most concrete and logical, and therefore the most dangerously persuasive. Like some other pious scientists who chose to see God’s hand acting directly in the fossil record—Louis Agassiz at Harvard, François Jules Pictet in Geneva, and Adam Sedgwick, who had been Darwin’s mentor in geology at Cambridge—Hitchcock wasn’t pleased.

Into the 1860 edition of his Elementary Geology, he inserted his rejoinder to Darwin’s book, based mainly on proof by authority. He noted that Pictet saw no evidence for transmutation in the fossil record of fishes. Agassiz said that the resemblances among animals derive from—where?—the mind of the Creator. “It is well to take heed to the opinions of such masters in science,” Hitchcock wrote, “when so many, with Darwin at their head, are inclined to adopt the doctrine of gradual transmutation in species.”

That was mild but firm, a dismissive shrug. Hitchcock would ignore Charles Darwin and encourage his readers to do likewise. More telling, more defensive, was his other response: he removed the trees figure from his own book. No more Paleontological Chart. It seems never to have appeared in another edition of Elementary Geology.

Darwin and Darwin’s followers owned the tree image now. It would remain the best graphic representation of life’s history, evolution through time, the origins of diversity and adaptation, until the late twentieth century. And then rather suddenly a small group of scientists would discover: oops, no, it’s wrong.

PART II

## [9]

Molecular phylogenetics, the study of evolutionary relatedness using molecules as evidence, began with a suggestion by Francis Crick, in 1958, offered passingly in an important paper devoted to something else. That was characteristic of Crick—so brilliant and recklessly imaginative that he sometimes influenced the course of biology even with his elbows.

You know Crick’s name from the most famous triumph of his life: solving the structure of the DNA molecule, with his young American partner James Watson, in 1953, for which he and Watson and one other scientist would eventually, in 1962, receive the Nobel Prize. Crick wasn’t wasting his time, in 1958, mooning about dreams of glory in Stockholm. He was still interested in DNA, but he had moved on from the sheer structural question to other big problems. He had bent his mind intensely, but with his usual sense of merry play, to the challenge of deciphering the genetic code.

The code, as you’ve heard many times but might need reminding, is written in an alphabet of four letters, each letter representing a component—a nucleotide base, in chemistry lingo—of the DNA double helix. The four letters are: A (for adenine), C (cytosine), G (guanine), and T (thymine). DNA’s full moniker is deoxyribonucleic acid, of course, and it’s worth understanding why. The two helical strands of the double helix, twining around a central axis in parallel with each other, are composed of units called nucleotides, linked in a chain, each nucleotide containing a base (that’s the A, C, G, or T), a sugar (that’s the deoxyribose), and a phosphate group (that’s the acidic part). The sugar end of one nucleotide bonds to the phosphate end of the next, forming the two long helical strands. I just called them parallel, but to be more precise, those strands are antiparallel to each other, since the sugar-phosphate binding gives them directionality—a front end and a back end—and the front end of one strand aligns with the back end of the other. The nucleotide bases, linked crossways by hydrogen bonds, hold the strands together. The base A pairs with T, the base C pairs with G, forming a stable structure, like the steps in a spiral staircase. This is the nifty arrangement that Watson and Crick deduced.

It’s not just a stable structure, though. It’s a wondrously efficient one for storing, copying, and applying heritable data. When the two strands are peeled apart, the sequence of bases along one of the strands (the template strand) represents genetic information ready to be duplicated or used. Watson and Crick noted that capacity with exquisite coyness in their 1953 paper. The paper was lapidary, only a page long, as published in the journal Nature, and included a sketch. Near the end, having proposed their double helix structure and the matchup of bases, always A with T and C with G, they wrote: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

But copying that material, for hereditary continuity, was one thing. Translating it into living organisms was another. Translated how? By what steps does the information in DNA become physically animate?

This mystery leads first to proteins. There are four kinds of molecule essential to living processes—carbohydrates, lipids, nucleic acids, and proteins—often collectively called the molecules of life. Proteins might be the most versatile, serving a wide range of structural, catalyzing, and transporting functions. Their piecemeal production, and the controls on the process of building and using them, are encoded in DNA. Every protein consists of a linear chain of amino acids, folded upon itself into an elaborate secondary structure. Although about five hundred amino acids are known to chemistry, only twenty of those serve as the fundamental components of life, from which virtually all proteins are assembled. But what sequences of the four bases determine which amino acids shall be added to a chain? What combination of letters specifies leucine? What combination produces cysteine? What arrangement of A, C, G, and T delivers its meaning as glutamine? What spells tyrosine? This fundamental matter—how do bases designate aminos?—became known as “the coding problem,” to which Francis Crick addressed himself in the late 1950s. Solving it was a crucial step toward understanding how organisms grow, live, and replicate.

There were questions within questions. Do the bases work in combinations? If so, how many? Two-base clusters, selected variously from the group of four and in specified order (CT, CG, AA, and so on) would allow only sixteen combinations, not enough to code twenty amino acids. Then maybe clusters of three or more? If three (such as CTC, CGA, AAA), do those triplets overlap one another, or do they function separately, like three-letter words divided by commas? If there are commas, are there periods too? Four letters, in every possible combination of three, yield sixty-four variants. Are all sixty-four possible triplets used? If so, that implies some redundancy; different triplets coding for the same amino acid. Does the code include a way of saying “Stop”? If not, where does one gene end and another begin? Crick and others were keen to know.

Crick himself had also started thinking beyond that problem, to the question of how proteins are physically assembled from the coded information, with one amino acid brought into line after another. How does the template strand find or attract its amino acids? How do those units become linked? He wanted to learn not just the language of life—its letters, words, grammar—but also the mechanics of how it gets spoken: its equivalent of lungs, larynx, lips, and tongue.

Crick was back in England by the mid-1950s, after a sojourn in the United States, and based again at the Cavendish Laboratory in Cambridge, where he had worked with Jim Watson. He had a contract with the Medical Research Council (MRC), a government agency with some mandate for fundamental as well as medical research. Solving the DNA structure, though it had brought scientific fame to Crick and Watson and would eventually bring the Nobel Prize, provided no immediate cure for Crick’s dicey financial situation, all the more acute since the birth of his and his wife Odile’s third child. He had to work for pay: a modest salary from the MRC and whatever small change the occasional radio broadcast or popular article might bring. Now he was sharing his office, his pub lunches, his fevered conversations, and his blackboard with another scientist, Sydney Brenner, rather than with Watson. One colleague at the Cavendish, upon early acquaintance with Crick, concluded that “his method of working was to talk loudly all the time.” When not talking, or listening to Brenner, he spent his time reading scientific papers, rethinking the results of other researchers, combing through such bodies of knowledge for clues to the mysteries that engaged him. He was not an experimentalist, generating data. He was a theoretician—probably the century’s best and most intuitive in the biological sciences.

Sometime in 1957 Crick gathered his thoughts and his informed guesses on this problem—about how DNA gets translated into proteins—and in September he addressed the annual symposium of the Society for Experimental Biology, convened that year at University College London. His talk “commanded the meeting,” according to one historian, and “permanently altered the logic of biology.” The published version appeared a year later, in the society’s journal, under the simple title “On Protein Synthesis.” Another historian, Matt Ridley, in his short biography of Crick, called it “probably his most remarkable paper,” comparable to Isaac Newton’s Principia and Ludwig Wittgenstein’s Tractatus. It was a commanding presentation of insights and speculations about how proteins are built from DNA instructions. It noted the important but still-fuzzy hypothesis that RNA (ribonucleic acid), the other nucleic acid, which seemed to exist in DNA’s shadow, is somehow involved. Might RNA play a role in manufacturing proteins, possibly by helping express the order (coded by DNA) in which amino acids are linked one to another? Amid such ruminations, Crick threw off another idea, almost parenthetically: ah, by the way, these long molecules could also provide evidence for evolutionary trees.

As published in the paper: “Biologists should realize that before long we shall have a subject which might be called ‘protein taxonomy’—the study of the amino acid sequences of the proteins of an organism and the comparison of them between species.”

He didn’t use the words “molecular phylogenetics,” but that’s what he was getting at: deducing evolutionary histories from the evidence of long molecules. Comparing slightly different versions of essentially the same protein (such as hemoglobin, which transports oxygen through the blood of vertebrates), as found in one creature and another, could allow you to draw inferences about degrees of relatedness between them. Those inferences would be based on assuming that the variant hemoglobins had evolved from a common ancestral molecule and that, over time, in divergent lineages, small differences in the amino sequences would have crept in, by accident if not by selective advantage. The degree of such differences between one hemoglobin and another should correlate with the amount of time elapsed since those lineages diverged. From such data, Crick suggested, you might draw phylogenetic trees. Humans have one variant of hemoglobin, horses have another. How different? How long since we shared an ancestor with horses? It could be argued, Crick added, that protein sequences also represent the most precise observable register of the physical identity of an organism, and that “vast amounts of evolutionary information may be hidden away within them.”

Having tossed off this fertile suggestion, Crick returned in the rest of the paper to his real subject: how proteins are manufactured in cells. That was his way. A passing thought, with the heft of a beer truck. Essentially he had said: Look, I’m not pursuing this protein taxonomy business, but somebody should.

## [10]

Somebody did, though not immediately. Seven years passed, during which several other scientists began noodling along various routes that would lead to a similar idea. Two of them were Linus Pauling and Emile Zuckerkandl, who gave their own fancy name to the enterprise—they called it “chemical paleogenetics”—and they converged on it by very different trajectories.

Zuckerkandl was a young Viennese biologist whose family had escaped Nazi Europe via Paris and Algiers. He got to America, did a master’s degree at the University of Illinois (long before Carl Woese would arrive there), then returned to Paris after the war for a doctorate. He found work at a marine laboratory on the west coast of France and studied the molting cycles of crabs, which involve a molecule analogous to hemoglobin. His interest drifted from crustacean physiology to questions at the molecular level, and he hankered to return to America. In 1957 Zuckerkandl finagled a chance to meet Pauling, who by then was a celebrated chemist with the first of his two Nobel Prizes already won. The prize had given Pauling some latitude to expand his own range of concerns, from lab chemistry at the California Institute of Technology to the wider world, and some leverage in pursuing those concerns. He had two in particular: genetic diseases such as sickle cell anemia and the threats posed by thermonuclear weapons, including radioactive fallout from testing. By the late 1950s, Pauling was raising his voice. He initiated a petition against atmospheric nuclear testing that more than eleven thousand scientists signed. He had become, along with Bertrand Russell, the provocative British philosopher, also a Nobel winner, one of the world’s most august peaceniks.

Pauling’s initial encounter with Zuckerkandl coincided with his increasing interest in genetics, evolution, and mutation—most pointedly, the mutations that might be caused by radiation released in weapons tests. His interest in disease led in the same direction, because sickle cell anemia is a problem that results from mutations in one of the genes for hemoglobin. Pauling found Zuckerkandl impressive enough that he offered the younger man a postdoctoral fellowship in chemistry at Caltech. Then, when Zuckerkandl arrived in Pasadena, intending to continue work on the crab-molting molecule, Pauling discouraged that project and said, “Why don’t you work on hemoglobin?”

Pauling suggested further that he take up a newly invented technique—still primitive but promising—that employed electrophoresis (separating molecules by their sizes, using electrical charge) and other methods to “fingerprint” such proteins, distinguishing one variant from another. Comparing protein molecules that way, Pauling figured, might allow researchers to draw some evolutionary conclusions. So Zuckerkandl went to work, learning the technique and applying it to hemoglobin in variant forms. Before long, he could see the close similarity between human hemoglobin and chimpanzee hemoglobin, and that human hemoglobin was less similar to hemoglobin found in orangutans. He could also tell a pig from a shark just by looking at the molecular fingerprints. Of course, there were easier ways to tell a pig from a shark, but never mind. Although it wasn’t such a precise methodology as he might have wished, this sort of molecular comparison was a start.

Over the next half dozen years, Zuckerkandl’s work thrived, and he published a series of papers with Pauling. Some of those were invited contributions to celebratory volumes, Festschriften, in honor of eminent scientists, generally on some occasion such as retirement or a big, round birthday. Such invitations came often because of Pauling’s own eminence, and he recruited Zuckerkandl as coauthor to do much of the thinking and most of the writing. In the meantime, Pauling won his second Nobel, this time the Peace Prize in recognition of his efforts against nuclear weapons proliferation and testing. That one didn’t add to his scientific reputation (in fact, he resigned from his Caltech professorship because university administrators and trustees disapproved of his peace activism), but it certainly helped amplify his public voice. He was a busy man, much in demand. The invitations—to speak, to visit, to contribute scientific papers for ceremonial volumes—continued. Because such papers didn’t normally go through the peer-review filter, they could be a little more bold and speculative than a typical journal article. One of them, written in 1963 to honor a Russian scientist on his seventieth birthday, was titled “Molecules as Documents of Evolutionary History.” Two years later, it was reprinted in English in the Journal of Theoretical Biology, giving it much broader reach and influence. Pauling and Zuckerkandl were wading into the same pond where Francis Crick had dipped his toe.

Their 1963 paper made an important distinction between molecules that carry genetic information—such as DNA or the proteins it encodes—and other molecules, such as vitamins, that cycle through a living creature and out the other end. Information molecules have histories that can be deduced; they have ancestors from which the variant forms, in this creature or that, have descended. Scrutiny of such molecules, wrote Zuckerkandl and Pauling, can tell us three things: how much time has passed since the lineages split, what the ancestral molecules must have looked like, and what were the lines of descent. The first of those three kinds of information became known as the molecular clock, although Zuckerkandl and Pauling hadn’t yet named it. The third kind implied trees.

Zuckerkandl continued reworking and developing these ideas, with Pauling as his coauthor and sponsor. In September 1964, before a distinguished and argumentative symposium audience at Rutgers University, he delivered a long paper that became the definitive version of their shared ideas and that, despite Zuckerkandl having done most of the writing, has been called the “most influential of Pauling’s later career.” In this paper, the two authors offered their memorable metaphor: if the minor changes in molecular variants are proportional to elapsed time over the eons, they said, what you have is “a molecular evolutionary clock.”

It was tentative, a hypothesis. The hypothesis was disputed at the Rutgers symposium and would be controversial in coming years, but it captured attention, it focused thought, and it promised a whole new way of measuring life’s history, if it was right. The molecular clock has since been called “one of the simplest and most powerful concepts in the field of evolution,” and also “one of the most contentious.” Crick himself later judged it “a very important idea” that turned out to be “much truer than people thought at the time.”

Emile Zuckerkandl, meanwhile, moved back to France. Along with Pauling and just a few others, he had helped launch a new scientific enterprise, and when a Journal of Molecular Evolution came into being, in 1971, he was its first editor in chief. His name isn’t familiar to the wider world, as Pauling’s is, but if you say “Zuckerkandl and Pauling” to a molecular biologist today, he or she will think “molecular clock.” Fitting as that may be, it overlooks the other important point: the other metaphor embedded in the long Rutgers paper, where Zuckerkandl wrote that “branching of molecular phylogenetic trees should in principle be definable in terms of molecular information alone.” This was a whole new way of sketching those trees, which rose and spread their branches as the clock ticked.

## [11]

Carl Woese came to the University of Illinois, in Urbana, in 1964, the same year Zuckerkandl delivered the paper at Rutgers. The enterprise that would become molecular phylogenetics—back then bruited under other names, such as Crick’s protein taxonomy, and Pauling and Zuckerkandl’s chemical paleogenetics—had begun to attract interest. Woese saw its deepest possibilities more clearly than anyone else. Molecular sequence information, he realized, could be used to read the shape of the past.

Woese was thirty-six years old and was hired with immediate tenure, which gave him some latitude to undertake risky, laborious research projects without need to worry about quick publications. His professorship was in the Department of Microbiology, though he had trained as a biophysicist, not a microbiologist, and had spent little time if any peering through microscopes at bacteria and other tiny bugs. He was more interested in molecular biology, then still in its early phase. It was a thrilling new branch of science, its methods just being invented, its cardinal principles just taking shape, and he wanted to be part of that. But the molecular clock wasn’t Woese’s topic, and the prospect of a molecular tree of life hadn’t yet captured his imagination. He was focused instead on the genetic code—and not just what he called the cryptographic aspect: the matter of which bases in which combinations specified which amino acids for building proteins. He wanted to go deeper in time and meaning; he wanted to understand how the code had evolved.

He was well aware that Francis Crick and others, including the eclectic Russian physicist George Gamow, had been working on the cryptographic aspect as a theoretical problem, treating it like an abstract intellectual game. That problem had been illuminated, but not solved, since Crick’s 1958 paper, by a new recognition of RNA’s role, as a messenger molecule somehow carrying DNA instructions to the site in a cell where proteins are built. But what was the structure of RNA, and how did it play that role? Gamow and the others were puzzled, and to them the puzzle was a thrilling game. They had even formed an elite, semifacetious little club—limited to twenty members, reflecting the twenty amino acids of life—for the private exchange of ideas about how coding and protein synthesis might work. They called it the RNA Tie Club—RNA because that molecule was still the mysterious intermediary; Tie because such neckwear evoked, and mocked, the clubby bond of an old school tie. As tokens of club membership, these scientists had embroidered neckties, all alike. They had individual tiepins, each representing one amino acid. They embraced their respective amino identities, at least jocularly: Serine and Lysine and Arginine, etcetera. Cute. Woese wasn’t a member.

The cryptographic riddle, so intriguing to Gamow and Crick and the others, was this: How could the four bases of DNA—represented by those four cardinal letters, A, C, G, and T—be combined in groups of at least three, with or without commas, to produce the twenty different amino acids? Woese addressed it alone. He knew that a team led by Marshall Nirenberg, a young biochemist at the US National Institutes of Health, had made better progress with an experimental approach than the RNA Tie Club was making with collegial theorizing. But he wanted to go deeper.

“I differed from the whole lot of them,” Woese wrote decades later, “in perceiving the nature of the code as inseparable from the problem of the nature and origin of the decoding mechanism.” The decoding mechanism? By that, he meant whatever organ or molecule translated the DNA information into real, physical proteins. Its origin? To him, at that time, this was the central biological concern. He wanted to understand not just how that decoding mechanism worked but also how it had come into being roughly four billion years ago. He recognized, more clearly than anyone else, that life could not have progressed beyond its simplest primordial forms without a translation system for applying the information in DNA.

No statement from Woese is more telling of his character, his cantankerous self-image as a scientific outsider, than the beginning of that sentence just quoted: “I differed from the whole lot of them …” He was a loner by disposition. He took a separate path. Not in the club. No RNA tie. He published a few papers in Nature on the coding question, and a comment in Science—all under his sole authorship, suggesting ideas, critiquing what others had done. He offered his own view in full, an evolutionary view, in a 1967 book, The Genetic Code, which was visionary, ambitious, closely reasoned, and mostly wrong. But in science, wrong doesn’t mean useless. Trying to imagine the origins of the genetic code brought Woese around, almost reluctantly, to the tree of life.

He needed some such universal diagram, Woese realized, as a framework for understanding the evolution of that one crucial system at life’s core—the translation system, turning DNA-coded information into proteins. Deep biology required deep history. This conundrum has been nicely expressed by Jan Sapp, a plant geneticist who became a historian of biology and came to know Woese well: “A universal tree would therefore hold the secret to its own existence.” History illuminating biology and vice versa. Evolutionary biology is history, after all. But there was a problem. For microbiology—bacteria and other single-celled creatures—a tree didn’t exist. The known trees didn’t encompass such organisms, or portray their diversity, to any satisfactory extent. Animals could be compared with one another on the basis of their physical appearance and behavior, as Linnaeus and Darwin had compared them; plants could be compared; fungi could be compared. They could be arranged in treelike patterns that reflected their relationships as deduced from such external, visible evidence. But that was impossible with microbes because, even under a high-powered microscope, so many of them looked so much alike.

There were a few basic shapes—rods, spheres, filaments, spirals—and those had served (reliably or not) to define major groups of bacteria. But at the finer level, the level of what we would think of as species, bacterial classification into a natural system, showing evolutionary relationships, was difficult. Arguably impossible. Even some of the experts had given up. It couldn’t be done on the basis of appearance and behavior. It couldn’t be done by way of physiological characteristics (which, in microbes, are what pass for behavior). It couldn’t be done at all, unless someone invented a new method.

“A slight diversion in my research program would be necessary,” Woese recollected later—a wry comment, because by then the diversion had lasted two decades.

## [12]

On June 24, 1969, Woese in Urbana wrote a revealing letter to Francis Crick in Cambridge. He had struck up an acquaintance with Crick about eight years earlier when Woese was an obscure young biologist at the General Electric Research Laboratory in Schenectady, New York, and Crick was already world renowned for the DNA structure discovery. It had begun as a tenuous exchange of courtesies, through the mail—Woese requesting, and receiving, a reprint of one of Crick’s papers on coding—but by 1969, they were friendly enough that he could be more personal and ask a larger favor. “Dear Francis,” he wrote, “I’m about to make what for me is an important and nearly irreversible decision,” adding that he would be grateful for Crick’s thoughts and his moral support.

What he hoped to do, Woese confided, was to “unravel the course of events” leading to the origin of the simplest cells—the cells that microbiologists called prokaryotes, by which they meant bacteria. Eukaryotes constituted the other big category, the other domain, and all forms of cellular life (that is, not including viruses) were classified as one or the other. Prokaryotes (pro being the Greek for “before,” karyon the Greek for “nut” or “kernel”) are cells without nuclei. Eukaryotes (eu for “true”) are the more complicated creatures, including multicellular animals, and plants, and fungi, plus certain single-celled but complex organisms such as amoebae, whose cells contain nuclei (hence the name, meaning “true kernel”). Prokaryotes (“before kernel”) seem to have existed on Earth before eukaryotes. Although bacteria are still around and still vastly successful, dominating many parts of the planet, they were thought in 1969 to be the closest living approximations of early life-forms. Investigating their origins, Woese told Crick, would require extending the current understanding of evolution “backward in time by a billion years or so,” to that point when cellular life was just taking shape from … something else, something unknown and precellular.

Oh, just a billion years further back? Woese was always an ambitious thinker. “There is a possibility, though not a certainty,” Woese told Crick, “that this can be done using the cell’s ‘internal fossil record.’” What he meant by that term was merely the evidence of long molecules, the linear sequences of units in DNA, RNA, and proteins. Comparing such sequences—variations on the same molecule, as seen in different creatures—would allow him to deduce the “ancient ancestor sequences” from which those molecules had diverged, in one lineage and another. And from such deductions, such ancestral forms, Woese hoped to glean some understanding of how creatures had evolved in the very deep past. He was talking about molecular phylogenetics, still without using that phrase, and he hoped by this technique to look back at least three billion years.

But which molecules would be the most telling? Which would represent the best internal fossil record? Frederick Sanger, a humble but visionary biochemist in England, had sequenced the amino acids of bovine insulin, and insulins are a fairly old family of molecules in animals and other eukaryotes, but they don’t go back nearly as far as Woese wanted. Other scientists had sequenced a protein called cytochrome c, also crucial in cell biochemistry among many creatures. But those didn’t satisfy Woese. He wanted something more basic, more universal—something that went all the way back, or nearly all the way, to the beginnings of life.

“The obvious choice of molecules here lies in the components of the translation apparatus,” he told Crick. “What more ancient lineages are there?” By “translation apparatus,” Woese meant the decoding mechanism, the system that turns DNA information into proteins—the same system that Crick had groped toward understanding in his 1958 paper “On Protein Synthesis.” Investigating the translation apparatus would in turn bring Woese around toward his starting point: his desire to learn how the genetic code itself might have evolved. Now, eleven years after Crick’s protein paper, the system was much better understood.

The components Woese had in mind were pieces of a tiny molecular mechanism common to all forms of cellular life. It’s called the ribosome. Nearly every cell contains ribosomes in abundance, like flakes of pepper in a stew, and they stay busy with the task of translating genetic information into proteins. Hemoglobin, for instance, that crucial oxygen-transporting protein. Architectural instructions for building hemoglobin molecules are encoded in the DNA, but where is hemoglobin actually produced? In the ribosomes. They are the core elements of what Woese called the translation apparatus.

Crick hadn’t used that phrase, “translation apparatus,” in his paper. He hadn’t even used the word ribosomes, but he touched upon them vaguely under their previous name, microsomal particles. These particles had only recently been discovered (in 1956, by a Romanian cell biologist using an electron microscope) and at first no one knew what they did. Then they became recognized as the sites where proteins are built, but a big question remained: how? Some researchers suspected that ribosomes might actually contain the recipes for proteins, extruding them as an almost autonomous process. That notion collapsed in 1960, almost with a single flash of insight, when Crick’s brilliant colleague Sydney Brenner, during a lively meeting at Cambridge University, hit upon a better idea. Matt Ridley has described the moment in his biography of Crick:

Then suddenly Brenner let out a “yelp.” He began talking fast. Crick began talking back just as fast. Everybody else in the room watched in amazement. Brenner had seen the answer, and Crick had seen him see it. The ribosome did not contain the recipe for the protein; it was a tape reader. It could make any protein so long as it was fed the right tape of “messenger” RNA.

This was back in the days before digital recording, remember, when sound was recorded on magnetic tape. The “tape” in Brenner’s metaphor was a strand of RNA—that particular sort called messenger RNA (one of several forms of RNA that perform various functions) because it carries messages from the cell’s DNA genome to the ribosomes. A ribosome consists of two subunits, one large, one small, fitted together and performing complementary functions. The small subunit reads the RNA message. The large subunit uses that information to join the appropriate amino acids into a chain, constituting the protein. The ribosomes and the messenger RNA, plus a few other pieces, constitute what Woese called the translation apparatus. By 1969, when Woese wrote to Crick, their crucial roles were appreciated.

Every living cell, including bacteria, including the cells of our own bodies, including those of plants and of fungi and of every other cellular organism, contains many ribosomes. They function as assembly mechanisms, taking in genetic information, plus raw material in the form of amino acids, and producing those larger physical products: proteins. In plainer words: ribosomes turn genes into living bodies. Because the proteins they produce become three-dimensional molecules, a better metaphor than Brenner’s tape-reader, for our own day, might be this: the ribosome is a 3-D printer.

Ribosomes are among the smallest of identifiable structures within a cell, but what they lack in size they make up for in abundance and consequence. A single mammalian cell might contain as many as ten million ribosomes; a single cell of the bacterium Escherichia coli, better know as E. coli, might get by with just tens of thousands. Each ribosome might crank out protein at the rate of two hundred amino acids per minute, altogether producing a sizzle of constructive activity within the cell. And this activity, because it’s so basic to life itself, life in all forms, has presumably been going on for almost four billion years. Few people, in 1969, saw the implications of that ancient, universal role of ribosomes more keenly than Carl Woese. What he saw was that these little flecks—or some molecule within them—might contain evidence about how life worked, and how it diversified, at the very beginning.

Another of Woese’s penetrating insights, back at this early moment, was to focus on a particular portion of ribosomes: their structural RNA. Usually we think of RNA in the role I mentioned above—as an information-bearing molecule, single stranded rather than double helical like DNA, carrying the coded genetic instructions to the ribosomes for application. Transient in space (through the cell) and transient in time (used and discarded). But that’s only one kind of RNA, messenger RNA, performing one function. There’s more. RNA can serve as a building block as well as a message. Ribosomes, for instance, are composed of structural RNA molecules and proteins, just as an espresso machine might be made of both steel and plastic. “I feel,” Woese confided to Crick in the letter, “that the RNA components of the machine hold more promise than (most of the) protein components.” Those RNA components held more promise for plumbing deep history, he reckoned, because they were so old and, probably, so little changed over time.

Woese saw the secret truth that RNA—not just a molecule, but a family of versatile, complex, underappreciated molecules—is really more interesting and dynamic than its famed counterpart, DNA. And this is where that family enters the story and begins taking its position near the center. Woese had decided he would use ribosomal RNA as the ultimate molecular fossil record.

“What I propose to do is not elegant science by my definition,” he confided to Crick. Scientific elegance lay in generating the minimum of data needed to answer a question. His approach would be more of a slog. He would need a large laboratory set up for reading at least portions of the ribosomal RNA. That itself was a stretch at the time. (The sequencing of very long molecules—DNA, RNA, or proteins—is so easily done nowadays, so elegantly automated, that we can scarcely appreciate the challenge Woese faced. Work that would eventually take him and his lab members arduous months, during the early 1970s, can now be done by a smart undergraduate, using expensive machines, in an afternoon.) Back in 1969, Woese couldn’t hope to sequence the entirety of a long molecule, let alone a whole genome. He could expect only glimpses—short excerpts, read from fragments of ribosomal RNA molecules—and even that much could be achieved only laboriously, clumsily, at great cost in time and effort. He planned to sequence what he could from one creature and another and then make comparisons, working backward to an inferred view of life in its earliest forms and dynamics. Ribosomal RNA would be his rabbit hole to the beginning of evolution.


Ribosome structure and function: converting messenger RNA to protein.

Gearing up the laboratory would be step one. Given his low level of administrative skill, he admitted to Crick, that much would be difficult. But besides lab equipment and money and administration, Woese perceived one other necessity. “Here is where I’d be particularly grateful for your advice and help,” he told Crick. He hoped to enlist “some energetic young product of Fred Sanger’s lab, whose scientific capacities complement mine.” By that, he meant: for this great sequencing effort, Woese would need a helper who knew how to sequence.

## [13]

Fred Sanger’s pioneering work was the standard at that time for efforts at sequencing RNA. Building on ideas from earlier researchers, Sanger had developed techniques for cutting a long molecule into short pieces, then separating those pieces by electrophoresis, pulling them apart within a column of gel. The gel column served as a racetrack for fragments of different sizes. With an electrical force applied, each fragment would be attracted toward one end and would migrate through the gel at its own speed, dependent on its molecular size and its electrical charge. As their differing speeds spread them apart, the fragments would show as a characteristic oval spot in a two-dimensional pattern, as captured on film. Each oval could then be read as a short squib of code, using other means of cutting and pulling. This was an advance on the same general method that Pauling had recommended to Zuckerkandl for distinguishing variant forms of a molecule by “fingerprinting.”

Fred Sanger had two things, but perhaps not much else, in common with Linus Pauling: chemistry and a pair of Nobel Prizes. Unlike Pauling, he was a quiet, unassuming man, from a Quaker upbringing in the English Midlands, who won both his Nobels in the branch of science he and Pauling shared—he was the only person awarded twice for chemistry. He received the first prize in 1958, at age forty, for work on the molecular structure of a protein—specifically, bovine insulin. To solve that structure, Sanger adapted some relatively primitive methods from other researchers, in an ingenious way, allowing him to determine which sequences of amino acids compose the two long branches of the insulin molecule. This was a Nobel-worthy achievement for what it said not just about blood-sugar regulation in cows but also about proteins in general: that they’re not amorphous things but have, each protein, a determined chemical composition. From proteins, Sanger turned to sequencing RNA, then DNA, and won his second Nobel in 1980 for the culminating phase of his DNA work. Soon after, at age sixty-five, he retired from science and turned his energies to gardening. He had a nice little home in a village near Cambridge.

“My work had sort of come to a climax,” he said later, and he didn’t care to morph into an administrator. He declined a knighthood, having no desire to be addressed as “Sir Fred” by friends and strangers. “A knighthood makes you different, doesn’t it,” he said, “and I don’t want to be different.” But that Cincinnatus retirement lay long in the future when Carl Woese, in his 1969 letter to Crick, daydreamed of getting a Sanger protégé to help him.

One of Sanger’s grad students had already come to Urbana, in fact, as a postdoc in the lab of another scientist within Woese’s department. That postdoc was David Bishop, brought over to assist Sol Spiegelman in sequencing viral RNA. Spiegelman had recruited Woese to the University of Illinois, rescuing him from obscurity at General Electric, in 1964. One year after Bishop’s arrival, Spiegelman left Illinois, returning to Columbia University in New York City, where his career had begun, and eventually taking Bishop with him. That might have yanked the Sanger techniques beyond Woese’s grasp. But in the interim months, Woese found a promising doctoral student named Mitchell Sogin and assigned him to learn what he could from Bishop before Bishop left. Molecular biology was in its formative phase, and though results could be announced in journal papers, the gritty details of lab methodology were often passed person to person, like the gift of stone tools or fire.

Mitch Sogin was a bright Chicago kid who had come down to the University of Illinois as an undergraduate on a swimming scholarship, planning to do premed. The swimming ended, the allure of medicine faded, but Sogin stuck around to earn a master’s degree in industrial microbiology within the Department of Food Science, part of the College of Agriculture. He worked on bacteria—specifically, the germination of bacterial spores, a matter of some practical interest to the food industry, given the implications for human health. Carl Woese, inhabiting a different department, almost a different universe, happened to have a lingering interest in spore germination from studies earlier in his career. For that slim reason, someone sent young Sogin to meet him. They clicked.

“And so I would go down and talk to him,” Mitch Sogin told me, almost fifty years later. “I liked him.”

Sogin was seventy at the time of our conversation, with a face that looked youthful but was now framed by thick, white hair. Behind his glasses, with his diffident smile, he resembled a professorial Paul Simon. We sat in his third-floor office in an old redbrick building on Water Street in Woods Hole, Massachusetts, headquarters of the Marine Biological Laboratory, a venerable research institution, where Sogin held the position of senior scientist and director of a center for comparative molecular biology and evolution. He seemed slightly bemused to have ended up there at Woods Hole, studying microbial communities of the oceans, microbial communities of the human gut, and microbial stowaways on space vehicles bound for Mars, as I nudged him to recall his early encounters with Carl Woese, back in 1968.

At that dicey moment in history, Sogin found himself, by age and geography, at the top of the rolls for his local Selective Service board. He hadn’t been drafted yet, but it seemed imminent, and this was before the first lottery made draft boards less arbitrary. “I had to make a sudden decision whether to stay in school or whether to go to Vietnam.” The war was at its ugliest; the Tet offensive in February that year had curdled the thinking of many young American males (including Mitch Sogin and me), and, unfair as it was, you could still get a deferment for graduate school. “Decided to stay in school,” Sogin told me. “It was simple.” He began work toward a doctorate under the mentoring of Woese. His topic was ribosomal RNA.

Woese had noticed something about Mitch Sogin during their early interactions: the kid was not just smart but also handy around equipment. Some combination of talents—dexterity, mechanical aptitude, precision, patience, a bit of the plumber, a bit of the electrician—made him good not just at experimental work but also at creating the tools for such work. Sol Spiegelman had ordered and paid for a collection of apparatus to be used for RNA sequencing by the Sanger method; but now Spiegelman was off to Columbia, leaving behind the tools.

“So Carl inherited that equipment. But he had no one that knew how to use it.” No one, that is, until Sogin joined his lab. “I was essentially responsible for importing all the technology”—importing it from Spiegelman’s lab, and other sources, into the Woese operation. Sogin learned as much as possible from Bishop about Fred Sanger’s techniques before Bishop decamped to New York, and then Sogin became Woese’s handyman as well as his doctoral student, assembling and maintaining an array of hardware to enable the sequencing of ribosomal RNA.

Woese himself was not an experimentalist. He was a theorist, a thinker, like Francis Crick. “He never used any of the equipment in his own lab,” Sogin said. None of it—unless you count the light boxes for reading films. Sogin himself had built these fluorescent light boxes, on which the film images of RNA fragments, cast by radioactive phosphorus onto large X-ray negatives, could be examined. He had converted an entire wall of bookshelves, using translucent plastic sheeting and more fluorescent bulbs, into a single big, vertical light box, like a bulletin board. They called it the light board. Viewed over a box or taped up on the light board, every new film would show a pattern of dark ovals, like a herd of giant amoebae racing across a bright plain. This was the fingerprint of an RNA molecule. Recollections from his lab members at the time, as well as a few old photographs, portray Carl Woese gazing intently at those fingerprints, hour upon hour.

“It was routine work, boring, but demanding full concentration,” Woese himself recalled later. Each spot represented a small string of bases, usually at least three letters but no more than about twenty. Each film, each fingerprint, represented ribosomal RNA from a different creature. The sum of the patterns, taking form in Carl Woese’s brain, represented a new draft of the tree of life.

## [14]

The mechanics of this effort in Woese’s lab, during Mitch Sogin’s time and for much of the next decade, were intricate, laborious, and a little spooky. They involved explosive liquids, high voltages, radioactive phosphorus, at least one form of pathogenic bacteria, and a loosely improvised set of safety procedures. Every boy’s dream. Courageous young grad students, postdocs, and technical assistants, under a driven leader, were pushing their science toward points where no one, not even Fred Sanger or Linus Pauling, had gone before. The US Occupational Safety and Health Administration (OSHA), though recently founded, was none the wiser.

The fundamental goal was to sequence variants of a molecule from the deepest core of all cellular life, compare those variants, and deduce the history of evolutionary relationships since the beginning. Woese had already settled on that one universal element of cellular anatomy, the ribosome, the machine that turns genetic information into proteins, but there remained a crucial decision: Which ribosomal molecule should he study? Ribosomes comprise two subunits, as I’ve mentioned—a small one snuggled beside a larger one, like an auricle and a ventricle of the heart, each constructed of both RNA and proteins. The RNA fractions include several distinct molecules of different lengths. At first, Woese targeted a short RNA molecule from the large subunit, known as 5S (“five-S”) for obscure reasons that I don’t ask you to contemplate. Just remember 5, a smallish number. That molecule proved unsatisfactory because its very shortness limited the amount of information it contained. The alphabet of nucleotides composing RNA is slightly different from that of DNA—it’s A, C, G, and U (for uracil) in place of T (for thymine)—and there was just not enough of the A-C-G-U alphabet in any little 5S sequence to distinguish different creatures from one another. So he switched to a longer molecule in the small subunit, and at the risk of causing your eyes to roll back in your head, I’m going to tell you its name. Why? Because it’s important, and once you’ve got it, you own it: 16S rRNA. There. Not so bad?

In English we say: “sixteen-S ribosomal RNA.” It’s a structural component of every bacterium on Earth, and bacteria were what Woese studied initially.

There’s a close variant, 18S rRNA, in the ribosomes of more complex creatures, such as animals and plants and fungi. This 16S molecule and its 18S variant, therefore, could serve as the reference standard, the great clue, for deducing divergence and relatedness among all cellular organisms. It was, arguably, the single most reliable piece of evidence, molecular or otherwise, for drawing a tree of life. And that recognition, though it never made the front page of the New York Times, was Carl Woese’s single greatest contribution to biology in the twentieth and twenty-first centuries.

The immediate goal for Woese, back in the early 1970s, was to extract ribosomal RNA from different organisms, to learn as much as possible about the genetic sequence of the chosen rRNA molecule from each organism, and to make comparisons from which he could gauge degrees of relatedness. He started with bacteria, because many kinds of bacteria are easy to grow in a lab, and their collective history is very ancient. Looking at bacteria from numerous different families allowed him the prospect of seeing contrasts, even in such a slowly evolving molecule as 16S rRNA. He and his team proceeded by extracting ribosomal RNA from the bacterial cells, purifying samples of the 16S molecules in each, and cutting those molecules into variously sized fragments with enzymes. Then they separated the fragments by electrophoresis, using an electrical field and a racetrack of soaked paper or gel.

In electrophoresis, a solution of mixed fragments is added to the racetrack, the power is turned on, and the electrical force pulls small fragments along faster than large ones, causing them to separate as distinct bands or ovals along the track. In Woese’s effort, each fragment comprised just a few of those A, C, G, U bases—maybe three, maybe five, maybe eight, maybe as many as twenty, but always a minuscule fraction of the full molecule. Those small fragments could then be pulled again, this time in a sideways direction, and their exact sequence would begin to come clear, based on the chemical and electrical differences among A, C, G, and U. Small fragments were easier to sequence by this method than one mammoth chain. AAG was easier to discern, as you might imagine, than AAUUUUUCAUUCG.

There were several stages of work. The primary run began the process of separating the fragments from one another. The secondary run, in a sideways dimension, revealed more about each fragment, which grew discretely recognizable as it raced not just down the racetrack but also now across. Those fragments, because of their radioactive content, showed as ovals burned onto the X-ray films. The oval-marked films would let an expert interpreter such as Woese infer the sequences—that is, to sort the As, Cs, Gs, and Us from one another and determine their order in each fragment. Once illuminated that way, a fragment became more like a word than like a shadowy amoeba. It had its own spelling. What was the spelling of this little word, this fragment, or that one? Was it CAAG? Or was it CAUG? Was it something a little longer and quite different—maybe CUAUGG? The answers were important because from those words, added up into paragraphs, Woese would deduce the degree of relatedness of the creatures from which they had come.

If the sequences were still ambiguous after a secondary run, as they often were, at least for longer fragments, then those were cut further, using other enzymes, and a third run was made. Rarely there might be a fourth run, but that was usually impracticable (as well as unnecessary) because the short half-life of the radioactive phosphorus that had been fed into these bacteria meant that its radiation faded quickly, and, after two weeks, the bits wouldn’t burn their images onto film. With experience, Woese developed a good sense of how to cut the fragments and get it all done in three runs at most.

Mitch Sogin and his successors did the culturing of microbes, the extraction of RNA, the cutting, and the electrophoresis. They added improvements to the methodology—different enzymes for cutting, modifications of the electrophoresis—and by 1973, the Woese lab had become the foremost user of Sanger-type RNA-sequencing technology in the world. While the grad students and technicians produced fingerprints, Woese spent his time staring at the spots. Was this effort tedious in practice as well as profound in its potential results? Yes. “There were days,” he wrote later, “when I would walk home from work saying to myself, ‘Woese, you have destroyed your mind again today.’” The years between 1968 and 1977 were lonely and long. Today sequencing is a snap, but Woese was ahead of his time, gathering data like a man crawling across desert gravel on his hands and knees. He couldn’t have done it without a strong sense of purpose.

Being his assistant or his student called on a certain gravelly fortitude too. Mitch Sogin described the deliveries of radioactive phosphorus (an isotope designated as P-32, with a half-life of fourteen days), which by 1972 amounted to a sizable quantity arriving every other Monday. The P-32 came as liquid within a lead “pig,” a shipping container designed to protect the shipper, though not whoever opened it. Sogin would draw out a measured amount of the liquid and add it to whatever bacterial culture he intended to process next. “I was growing stuff with P-32. It was crazy,” he said, tossing that off as a casual memory. “I don’t know why I’m alive today.” Because the bacteria were cultured in growth media lacking other phosphorus, a vital nutrient, they would avidly seize the P-32 and incorporate it into their own molecules. Sogin would then extract and purify the ribosomal RNA, “all the while not contaminating the laboratory.” That was the hope, anyway. For separating 16S from the other ribosomal fractions, he used “home-built electrophoresis units,” cylinders of acrylamide gel through which the different molecular fragments would migrate at different speeds. (Acrylamide is a water-soluble thickener, sometimes used in industry as well as in science.) Then he would freeze the gel and attempt to slice it, like bologna, with a very precise knife. The slicing was difficult: slices would fall off when they shouldn’t, he had to work the material at just the right temperature, and “this was pretty radioactive stuff.” Sogin then cut the 16S molecules into fragments with an enzyme, and those fragments would run a race of their own, not through cylinders of gel but along a racetrack of special, absorbent paper.

One end of the long paper strip went into a receptacle known as a Sanger tank (as developed by Fred Sanger), containing a liquid buffer. The strip passed over a rack, beyond which its far end dropped into another Sanger tank, and both tanks were wired to an apparatus that provided the electrical pull. At the bottom of the tanks were high-voltage platinum electrodes, covered by three inches of liquid buffer and then at least fifteen inches of Varsol, a solvent not unlike paint thinner, intended to cool the paper strip. “Varsol is both volatile and explosive,” Sogin said. The power source delivered around 3,500 volts and plenty of amps, he recalled—“certainly enough to kill you.” Also enough, with an errant spark into the Varsol, to blow you up.

This whole panoply of dangerous, intricate machinery dwelt within a shielding hood that could be closed behind large sliding doors, floor to ceiling, in a nook off the main lab known as the electrophoresis room. Set up the system, close the doors, turn on the juice, hope for the best. “I was too stupid to be afraid of anything,” Sogin told me. “Too naïve. Too young. Immortal.” He was also lucky. Nobody got hurt.

Around the time Sogin finished his doctorate and prepared to leave, Woese hired a young woman named Linda Bonen, a walk-in from a different building, to take on some of the technical work. Raised in rural Ontario, she had come down to the University of Illinois and gotten a master’s degree in biophysics. Woese trained her for this new lab work himself—how to chop the RNA into fragments, how to run the electrophoresis in two dimensions, how to prepare the films, even a bit about how to interpret them, deducing which spot on a film represented which fragment, which little blurt of letters. Was it UCUCG, or was it UUUCG? Tricky to tell. But here’s GAAGU, obviously different. Woese coached her patiently on the tasks and their meaning.

“He was very good about bringing me along,” Bonen recalled four decades later, when I visited her at the University of Ottawa, where she was by then a biology professor herself, gray haired, deeply expert in molecular genetics, gentle mannered as a schoolteacher. “The end product would be a ‘catalog’ for microbe X,” she said, meaning simply a list of the different fragments found within the 16S rRNA molecules of that creature. A catalog. If the fragments resembled words, these catalogs were the paragraphs. Comparing one catalog with another revealed the degree of similarity between any two organisms, by a very precise standard, and more dissimilarity could be taken to reflect more distance in evolutionary time. Where had the great limbs diverged from the trunk, the big branches from the limbs—and why there, and why then, and leading to what creatures? Beyond the mind-numbing methodology of data collection, those were the questions Woese hoped to answer.

What was he like, I asked Bonen, as a boss and a teacher?

“Well, he never came across as a boss,” she said. “He was very soft-spoken and quiet, reserved. I’m sure you’ve …” She hesitated. “Did you know him yourself? Did you ever meet him?”

Never. I didn’t explain to her, but the reason was simple: Woese died, in late 2012, an old man taken down hard and fast by pancreatic cancer, just before I picked up the trail.

“To everybody, he was Carl,” she said. “He was not a boss.”

Bonen showed me a photograph, a memento from her personal files: the youngish Carl Woese in his lab, bathed by yellow-green light, jaw set firmly, gazing up at a pattern of dark spots. Short brown hair, striped sport shirt, handsome and jaunty enough to have stood onstage amid the Beach Boys. Almost apologetically, she said: “That’s the only good picture I have.” This was all different from what I had expected. My mental image was of the later man: the shy, crotchety, and august Dr. Carl Woese.

He was shy, yes, Bonen said. But “august,” no, that was wrong, not a word she would ever … and here again her voice fell away. Then she added: “I only knew him in a short period of time.”

## [15]

Ken Luehrsen, soon after Linda Bonen’s short period, had a different sort of experience in the Woese lab. He was an undergraduate at Illinois when he first encountered Woese as one of the instructors for a seminar in developmental biology, well outside Woese’s field of expertise. The logic behind this mismatch, according to Luehrsen, was that “other professors just liked to hear Carl’s take on things so they might incorporate some of his ideas into their own research.” Woese was notoriously brilliant, full of ideas, but jealous of his expended effort. “Undoubtedly, Carl found an opportunity to get a teaching credit where he didn’t have to do too much work.” In a seminar, students would be assigned to make presentations explicating this journal paper or that one, and Woese could easily moderate the discussion. He hated classroom teaching of the more arduous sort—preparing and delivering lectures, God forbid—because “he felt it took him away from his real love: understanding the origin and evolution of life.”

After the seminar acquaintance, Luehrsen went to this formidable figure and asked to do an honors project under his guidance. Woese not only accepted him but also, to Luehrsen’s surprise, “he plopped me down in his office,” a very small room containing two desks, both covered with chaotic stacks of papers, and said (either seriously or as a tease) that it was so he “could keep an eye on me.” Luehrsen was befuddled. Should he really be there? Should he scram whenever the phone rang and give Woese his privacy? His discomfort eased when he saw that Woese himself spent little time in that office and most of his time in the lab, “reading 16S rRNA fingerprints at his light board.”

After Woese’s death, Ken Luehrsen wrote a short memoir describing the man’s work, his temperament, and their interactions so long ago, for publication with other Woese tributes in a scientific journal. He brought it all to mind again when I tracked him down in San Carlos, California, on the edge of Silicon Valley, where he was now a senior scientist and biotech inventor in the late afternoon of his career, consulting for a small company lodged behind glass doors in an office park. By that time, he held many patents in biotechnology, for methodologies to create antibodies and other molecular products, and lived comfortably in an old counterculture enclave across the peninsula, a place known as Half Moon Bay, from which he could commute to the action. He worked when he felt like it. At this firm, he was the grizzled elder, surrounded by smart young colleagues seated in carrels, for whom “Woese” was at most a dimly recognizable name, like “Darwin” or “Fibonacci.” Tall and thin, with a goatee, relaxed and a little sardonic, Luehrsen suggested we escape downtown for sushi—after which we talked for most of the afternoon.

“I may have been a junior at the time,” he said about his first acquaintance with Woese. “I didn’t know anything.” Despite Luehrsen’s ignorance, the great man invested some effort in him; a private tutorial was less abhorrent to Woese than lecturing at banks of indifferent faces. “He explained to me what he was doing. I maybe understood a quarter of it.” But the youngster paid close attention and caught on fast. “I think he saw somebody who was interested, and I was a pretty hard worker.”

It was 1974 when Luehrsen joined the Woese lab as an undergraduate assistant, paired with a graduate student and assigned the unenviable job of extracting radioactive rRNA from bacterial cultures. They would dump ten millicuries (a large dose) of P-32 into this culture or that and, after overnight incubation to let the bacteria suck it up, spin the mixture in a centrifuge to gather the hot bacteria into a little pellet. After dissolving the pellet in a buffer, they would squash that brew through the laboratory version of a French press, not too unlike the one you might use for coffee. This served to rip open the bacterial cells and set their innards adrift. Luehrsen and his partner would then pull out the ribosomal RNA by chemical extraction, after which the different fractions—the 16S molecules versus the others, including that shorter one, known as 5S—were separated using Mitch Sogin’s home-built cylinders of acrylamide gel. In addition to acrylamide (today recognized as a probable carcinogen), they were working with phenol, chloroform, ethanol, and the radioactive phosphorus. “What a mess that often was! The Geiger counter was always screaming,” Luehrsen wrote in his memoir.

One of the bacteria he cultured and squashed was Clostridium perfringens, the microbe responsible for gas gangrene, an ugly form of necrosis that takes hold in muscle tissue made vulnerable by wounds, especially the sort that lay open among injured soldiers on battlefields. When he realized this, Luehrsen complained, but Woese “just chuckled and said not to worry” in the absence of an open wound. He had been to medical school for “two years and two days,” Woese said, and he could assure Luehrsen that Clostridium perfringens was unlikely to give him gangrene. Luehrsen took the episode as a lesson—not a lesson to trust Woese but to rely on his own perspicacity more—and never probed the matter of why Woese had quit medical school two days into his third-year rotation in pediatrics.

After graduating from Illinois in 1975, Ken Luehrsen stayed to work toward a PhD under Woese’s supervision, just as Woese shifted the lab’s focus, slightly but critically, in a way that would lead toward his most startling discovery. So far, they had targeted their molecular analyses on common bacteria and a few other single-celled organisms such as yeast—easy to obtain, easy to grow in the lab. But that was just a preliminary effort as they refined their methods. “One of the things he wanted to do was to look at unusual bacteria,” Luehrsen told me. Woese hoped this might give a view “deep into evolution,” where he could see “deep divergences” between one big branch of life and another. So he struck up a collaboration with a colleague in the Microbiology Department, Ralph Wolfe, one of the world’s leading experts in culturing a group known as the methanogens.

Methanogens: their name derives from an odd aspect of their biochemistry, producing methane as a byproduct while metabolizing hydrogen and carbon dioxide in environments lacking oxygen. To say it more plainly, these bugs generate swamp gas in muddy wetlands, from which it bubbles up, and similar gas in the bellies of cows, whence it emerges by belch and fart. Certain methanogens also thrive beneath the Greenland ice cap, deep in the oceans, and in other extreme environments, such as hot desert soils. Despite these shared metabolic traits, Ralph Wolfe advised Woese, there was an odd discontinuity among the assemblage of methanogens—discontinuity in terms of their shapes. Some were cocci (spherical), some were bacilli (rod shaped). Since the cocci and the bacilli were considered two distinct kinds of bacteria, microbiologists had been puzzled about how to classify the methanogens—together by metabolism or separately by shape. That conundrum captured Woese’s interest.

Having told me this much, and more, Ken Luehrsen finished our conversation and sent me away with some gifts. One was a black-and-white print of a photo he took in the mid-1970s, a snapshot, showing Woese at his light board, engrossed before a pattern of dark spots, with a handful of felt-tip pens for color coding what he saw, a pencil for data registry behind his right ear. Luehrsen’s other gift was a single yellowing sheet—not a copy, the original—from his own notebook of the time. It was a catalog of fragments from an organism, more of those telling blurts of the four coding letters, neatly recorded in two columns. UCUCG. CAAG. GGGAAU, and dozens more. At the top, also hand lettered, an abbreviation indicated the name of the organism as it was known at the time: Methanobacterium ruminantium. Later, I realized that, notwithstanding the name, this was no bacterium. Luehrsen had given me the genetic rap sheet on a separate form of life.


Annotating RNA fragments on a “fingerprint” film.

## [16]

How do you classify the methanogens? Where do they fit on the tree of life? To what other little bugs are they most closely related? Those questions, which Woese and his colleagues were asking themselves in the mid-1970s, fell within the scope of an important discipline with a dry name: bacterial taxonomy. That’s the enterprise of sorting bacteria into nested groups: species, genera, families, etcetera. You name something Methanobacterium ruminantium, and then where do you put it?

This may sound like an exercise in arcana, a marginal activity of risible triviality beside which stamp collecting looks like an adventure sport. Bacteria are tiny, relatively simple, invisible. But if being invisible made things unimportant, gravity and microwaves would be unimportant too. It’s useful to recall that most life-forms on Earth are microbial, that they determine the conditions of existence for the rest of us, and that even the human body contains at least as many microbial cells (those tiny passengers that live in your gut, on your skin, in the follicles of your eyelashes, and elsewhere) as human cells. Your environment is highly microbial too. Your food. The air you breathe. Microbes run the world, and a very large portion of those microbes are bacteria. Some of them serve as helpful partners of humanity. Some are benign. Some are rapacious, ready to poison your blood, fill your lungs, kill you. So it’s no small matter, telling one bacterium from another.

Scientists once believed it might be possible to do this from visual evidence obtained through a microscope. They even presumed that the concept of species, as understood for animals and plants and fungi, could be applied to bacteria. These were useful simplifications in their era—like the simplifications of Newtonian physics, before correction by Einstein—but that era was a long time ago.

The early hero in the field was a man named Ferdinand Julius Cohn, a botanist and microbiologist at the University of Breslau (now Wrocław, Poland) during the late nineteenth century. Cohn is an appealing figure, and only partly because his important contributions have been overshadowed by those of better-remembered contemporaries whose accomplishments were more practical and dramatic: Louis Pasteur, Robert Koch, Joseph Lister. They worked on disease, agriculture, and wine. Cohn worked mainly on describing and classifying microscopic organisms. No one makes Hollywood movies about bacterial taxonomists.

Cohn wasn’t the first researcher to classify bacteria, making distinctions between kinds, trying to place the whole group in its proper position on the tree of life. But his effort was more hardheaded and percipient than the others, and he did much to bring bacteriology out of a fog of confusions that had lingered for more than a century, ever since startled observers such as Leeuwenhoek had noticed these little creatures through simple microscopes. Several insights and adjustments of method helped him make progress. Microscopy improved, with better lenses and precision instruments in which they were mounted. Cohn’s lab started culturing bacteria on solid media such as slices of cooked potato, not in liquid nutrient, the old way. That allowed Cohn to choose, cultivate, and consider different strains separately. Also, he recognized that physiological and behavioral characteristics as well as structural ones could be useful for distinguishing bacterial species: How do they grow in different media? How do they move? By this time, too, Cohn had embraced Darwin’s theory of evolution, and so it made sense to him that bacterial strains might change and adapt over time. This was incremental change, very different from the sort of utter transformation—one bacterial form suddenly morphing into another—that some scientists imagined to occur. Cohn didn’t buy transformation. He saw bacteria as fundamentally stable in their identities. Finally, he published his system, dividing them into four tribes: spherical, rod shaped, filamentous, and spiral, each of which got an imposing Latinate name. Within the tribes, he drew finer distinctions, separating them into genera and species.

Not everyone in the field accepted Cohn’s classification of bacterial species or his conviction about their stable identities, and the idea of shape-shifting bacteria lingered for more than a decade. The longer judgment of science historians was good to him, as a man and a scientist, noting his “reserve” against self-promotion, his modesty, his eloquent lecturing, and his success in “disentangling almost everything that was correct and important out of a mass of confused statements on what at that time was a most difficult subject to study.” Besides arguing for the reality of bacterial species and sketching a way to classify them, Cohn did much, along with Pasteur, to kill the resilient delusion that new life-forms arise by spontaneous generation. They don’t, he showed. When bacteria seem to appear out of nowhere, it’s because they have arrived from somewhere: contamination, floating through the air, reawakening spores. Cohn’s work was “entirely modern in its character and expression,” according to an authoritative chronicler of the field, writing in 1938, “and its perusal makes one feel like passing from ancient history to modern times.” But what looked modern in 1938, of course, doesn’t look modern now.

Even the devoutly empirical Ferdinand Cohn made mistakes. For one: after all his research, he still believed, as many of his colleagues did, that bacteria belong to the kingdom of plants. So his tree of life, by later standards, was badly wrong. For another: the premise of radical transformation, one bacterial form to another, turns out to be vastly more complicated than he could imagine.

## [17]

Chaos” was the name of the group into which Linnaeus, the great systematizer, in the 1774 edition of his Systema Naturae, had lumped Leeuwenhoek’s bacteria and other little creatures. That was a durable judgment. Even well into the twentieth century, decades after Ferdinand Cohn, experts were still arguing about whether bacterial taxonomy was a meaningful enterprise or hopelessly chaotic.

Beginning in 1923, the standard source for identifying bacteria was a thick compendium, Bergey’s Manual of Determinative Bacteriology, edited by the bacteriologist David Hendricks Bergey. But as microbiology progressed, it became clear that the Bergey’s system was vague, inconsistent, and, on some fundamentals, inaccurate. It didn’t offer a tree of bacterial life. It was only a glorified field guide. Still, other researchers who critiqued Bergey’s Manual, and then tried to improve on it, found the critiquing much easier than the improving. The task of bacterial classification was just so difficult. There was almost no fossil record of bacterial ancestors. There weren’t enough differences of external shape and internal anatomy, even as seen through powerful microscopes, to support fine distinctions. Physiological characters could also be misleading, if they reflected parallel adaptations rather than shared ancestry. What did that leave for a classifier to use? (Hint: Carl Woese would offer an answer, but not until 1977.) This conundrum came to a head in 1962, when two of the world’s leading microbiologists, C. B. van Niel and Roger Stanier, essentially threw up their hands in despair.

Van Niel was a Dutchman, educated in Delft, who in 1928 decamped to California, where he taught at a marine biological station that was part of Stanford University. His particular interests were bacterial physiology and taxonomy. Roger Stanier was a younger Canadian who became van Niel’s student, then his special protégé, then his collaborator. In 1941, when Stanier was still just twenty-five years old, he and van Niel coauthored an influential paper on bacterial classification.

That paper stood as definitive for a generation—until both authors renounced it. Stanier himself later admitted some embarrassment about it, all the more so because he had arm-twisted van Niel to sign on as coauthor—student and teacher together, although the work was mainly Stanier’s. What the paper contained, besides a pointed critique of Bergey’s Manual, was a shiny new proposal for classifying bacteria—not just a checklist or a field guide but a “natural” system reflecting their evolutionary relationships. That system divided the familiar bacteria into four major groups (as Ferdinand Cohn had done) and placed them in a kingdom of simple creatures along with just one other group: the blue-green algae.

Algae? Yes, the blue-green algae, as they were then called, had long been an ambiguous group, because they seemed to straddle the line between bacteria and plants. (This was partly what allowed Cohn to believe that all bacteria were plants—the blurry lines around blue-green algae.) Algae was a catchall term for a loose assemblage of creatures that photosynthesize, including these tiny blue-green creatures, but that didn’t mean all algae shared a single common ancestor. Did they? Stanier and van Niel said no. By their new definition of things, blue-green algae were more similar to bacteria than to other algae, and these two groups should be lumped together in a kingdom of their own, apart from everything else. Eventually they labeled such cells procaryotic—meaning “before kernel,” as I’ve mentioned—and set them in contrast to eucaryotic cells, comprising all else. (Their spellings were later corrected, from more accurate transliteration of the Greek roots, to prokaryotic and eukaryotic.) The kernel in question was a cell nucleus. Just as a bacterium doesn’t have one, neither do the creatures that were then known as blue-green algae (and are now classified as cyanobacteria). Advances in microscopy since the end of World War II, including electron microscopy, had given microbiologists a better view of those distinctions and others, making possible a fresh analysis of what a bacterium is—and what it isn’t. Stanier and van Niel offered that fresh analysis along with the prokaryote category in a new paper, published in 1962, titled “The Concept of a Bacterium.” By their lights, the “abiding intellectual scandal of bacteriology” was that no such concept had ever been clearly delineated. What was a bacterium? Um, hard to say.

They tried to correct that by placing bacteria and blue-green algae together as prokaryotes, and setting them in contrast to the alternative category, eukaryote, which encompasses all other forms of cellular life. The chief distinguishing features of a prokaryote, according to Stanier and van Niel, were: (1) no cell nucleus, (2) cell division by simple fission, rather than the elaborate process of chromosome pairing known as mitosis, and (3) a cell wall strengthened by a certain sort of latticework molecule with a fancy name, peptidoglycan. I know, it looks like the moniker of a flying reptile from the Jurassic. Forget about it for now, and when peptidoglycan comes back as an important clue toward understanding the deepest structure of the tree of life, and the twig on the branch on the limb from which we humans have sprouted, I’ll remind you.

The dichotomy between prokaryotes and eukaryotes, creatures without cell nuclei and those with, relatively simple beings and relatively complex, became a fundamental organizing principle of biology. Stanier and his two coauthors of a textbook would later say that it “probably represents the greatest single evolutionary discontinuity to be found in the present-day living world.” It was also a salubrious reminder to humans of our inescapable linkage to other creatures, including some very humble ones. We are, at the most basic level of classification, eukaryotes. So are amoebae. So are yeasts. So are jellyfish, sea cucumbers, the little parasites that cause malaria, and rhododendrons. To an average person, the gap between an amoeba and a bacterium may seem narrow (partly because most of us have never, or at least not since high school biology, looked through a microscope at either), but the prokaryote-eukaryote distinction reveals it as oceanic. You could think of the living world—and, beginning from Stanier and van Niel’s 1962 paper, biologists did think of the living world—as divided into proks and euks.

Besides putting that idea into play, “The Concept of a Bacterium” is notable for having signaled surrender, by Stanier and van Niel, in the battle of bacterial taxonomy. About this they were candid, confessional, and brusque. Ever since Leeuwenhoek, microbiologists had been seeking the best way to classify bacteria. Ever since Darwin, they had been arguing about how one bacterium was related to another. Enough was enough. “Any good biologist finds it intellectually distressing to devote his life to the study of a group that cannot be readily and satisfactorily defined.” C. B. van Niel himself had devoted forty years. He and Stanier now alluded to the “elaborate taxonomic proposal” they had published back in 1941, “which neither of us cares any longer to defend.” Never mind that. They admitted having “become sceptical about the value” of any such formal systems, or the effort spent to develop them, although they still affirmed the importance of figuring out just what the devil bacteria are.

This skepticism, this taxonomist’s despair, had been wiggling up inside van Niel for a long time. Two decades earlier, even as he was signing onto that first elaborate proposal, he had confessed his gloom to Stanier in a letter: “Many, many years ago I often went around with a sense of futility of all our (my) efforts. It made me sick to go around in the laboratory (this was in Delft) and talk and think about names and relations of microorganisms.” Was any of it real? Was there any value to putting bacteria into labeled boxes? “During those periods I would go home after a day at the lab, and wish that I might be employed somewhere as a high-school teacher.” Not that he would enjoy such teaching, he realized, but at least “it would give me some assurances that what I was doing was considered worth-while.” Nowadays we might see that as a signal of bipolar disorder, but it’s just as likely that van Niel simply viewed bacterial taxonomy with great clarity.

Under their revised spellings, prokaryote and eukaryote, those two became enshrined for a generation as the most fundamental categories of life. Eukaryotes had cell nuclei. Prokaryotes did not. That dichotomy seemed to represent, as Stanier and his coauthors had written, the greatest single evolutionary divide in the living world. There were two basic kinds of creature, the proks and the euks, and there was nothing between.

What makes this worth knowing is that Carl Woese proved it wrong.

## [18]

As of early 1976, with Ken Luehrsen and others still helping, Woese had done his unique form of catalog analysis on samples from roughly thirty species, using differences in ribosomal RNA molecules to measure their relatedness. Most were prokaryotes, but he also looked at a few eukaryotes (which carried that slightly different molecule in their ribosomes, 18S rRNA instead of 16S), including yeast, for purposes of gross comparison. He could tell a prok from a euk just by inspecting the spots on a sheet of film. And he was eager to see those “unusual bacteria,” the methanogens, about which Ralph Wolfe had alerted him.

The tricky thing about methanogens was that, since oxygen poisoned them, they were hard to grow in a laboratory. But Wolfe’s lab team included an ingenious doctoral student, Bill Balch, who had solved that problem by devising a way to culture methanogens in pressurized aluminum tubes with black rubber stoppers, and using syringes to move things in and out. Balch gave the methanogens an atmosphere of hydrogen and carbon dioxide instead of oxygen, plus a liquid growth medium, and they thrived. Woese sent his own postdoc, a rangy young man named George Fox, trained in chemical engineering, to work with Balch on growing some of these methanogens and tagging them with radioactive phosphorus. Fox, Ken Luehrsen, and other members of the Woese lab then combined their efforts on the rest of the process: extracting the radioactive RNA, purifying it to get concentrations of 16S and 5S molecules, chopping those molecules into pieces, running the electrophoresis to separate the fragments, and printing the spots onto films. Their first methanogen carried a formal name so long (Methanobacterium thermoautotrophicum) that even Woese himself dismissed that as “a fourteen-syllable monstrosity” and preferred using a shorter label, denoting the particular laboratory strain: delta H. Examining its primary fingerprint on his light board, Woese noticed something odd.

He was practiced enough by now at reading such fingerprints that he could immediately recognize a certain pair of small fragments, common to all bacteria, that “screamed out” their membership in the prokaryotes. He looked for them on the primary film from delta H. They were missing. Intrigued but patient, he waited for the secondary fingerprint, with the fragments pulled sideways to reveal more detail. He got that from his technician several days later. On June 11, 1976, he taped the primary film up on his light board again, with the secondary now in front of him on the light table, and began trying to interpret what he saw. He intended, as usual in this stage of the process, to use the secondary film as a guide for inferring the base sequences of the fragments in the primary pattern. Apart from his board and his table, the room was dark. His face, we can imagine, reflected an eerie glow. Quickly he noticed more oddities.

The two missing fragments were still missing, but it wasn’t just that. Woese turned to a different part of the pattern, expecting to see another familiar fragment—a “signature” sequence in all prokaryotes. Not there. Instead, he found a strange fragment, a longish sequence that shouldn’t have been present at all. “What was going on?” he later recalled wondering. This methanogen rRNA just “was not feeling” prokaryotic. And the more fragments he sequenced, the less prokaryotic it felt. By this time, he knew the sequences of ribosomal RNA in bacteria so intimately that his “feel” for the molecule was a persuasive standard of normality. And something in this particular creature, delta H, was abnormal. Some bacterial fragments were appearing where expected, as expected, yes. But some others looked eukaryotic, suggesting a completely distinct form of life: a yeast, a protozoan, what? And still others were just weird. What was this RNA? he wondered, and what manner of organism did it represent? It couldn’t be from a prokaryote. It wasn’t eukaryotic. It wasn’t from Mars, because it contained too many familiar stretches of RNA code. “Then it dawned on me,” he wrote. There was “something out there”—out there in the teeming ecosystems of planet Earth, he meant—other than prokaryotes and eukaryotes. A third form of life, separate.

Woese called this, whimsically, his “out-of-biology experience.” It would be the watershed moment of his scientific life.

## [19]

After his death in December 2012, Woese’s files of scientific correspondence, manuscripts, journal articles, and other materials went to the University of Illinois Archives to be indexed, curated, and preserved. The archives are held in several different locations, one of which is the Archives Research Center, a sort of annex, housed in an old, barnlike building of red brick on Orchard Street near the south edge of the campus. A sign in front identifies this, confusingly but historically, as the Horticulture Field Laboratory; a bank of yew bushes and a riot of hostas guard the entrance. Inside, filed neatly in thirty-four boxes that can be accessed by request, are the Carl Woese Papers. I was working there at a table one hot July afternoon, reading through letters, looking for clues about the human side of this peculiar man, when John Franch arrived, wearing a dark T-shirt and a ball cap. Franch is the assistant archivist who was sent to clean out Woese’s lab after the funeral, and who knows the material found there better than anyone else. He had heard about my interest and wanted to show me something.

He led me toward the back of the building, where the roof arches high, and unlocked a door. This was one of the “vaults,” he told me, that formerly served for storing fruit—apples in particular—from the horticultural research orchards from which Orchard Street got its name. At one point, there were 125 varieties of apple grown just behind the building, and they came in by the basket and the crate to be stored here or pressed for cider and vinegar. Beyond the door, we entered an air-conditioned room, empty of apples now but lined along its left side with tall metal shelves, along its right side with tables. The shelves held hundreds of large, flat yellow boxes—the original packaging of Kodak medical X-ray films—representing the library of Woese’s RNA sequencing fingerprints. Each box was labeled along its edge with a date and the organism whose fragments were depicted.

Across the room, some films lay on the tables, where Franch had been working over them. He showed me three large sheets, carefully taped together, forming a triptych of images. I stared at the patterns of dark spots: amoebae galloping on a plain. To me, they made no particular sense. But to Woese, they had spoken eloquently of identity, relationship, evolution. If something was odd, he would have seen it.

This is delta H, Franch said.

## [20]

Immediately after his epiphany, Woese shared it with George Fox, the postdoc he had assigned to work with Bill Balch on growing the methanogens. As recalled later by Fox, Woese “burst into my room in the adjoining lab” with the announcement that they had something unique. From there he proceeded throughout the lab, among his young students and assistants, “proclaiming that we had found a new form of life. He then pointed out,” by Fox’s memory, tart and amused, “that this was of course contingent on my having not screwed up the 16S rRNA isolation.” Being cautious, they repeated the whole process with delta H and got the same result. So no, Fox hadn’t screwed up.

“George was always skeptical,” Woese himself wrote later about their reactions to the discovery, adding that he valued such skepticism as good scientific instinct. Fox’s doctorate in chemical engineering suited him well to offset epiphanic leaps, even by the boss, with empirical caution. In fact, their shared instinct for skepticism about such a startling result helps explain why these two men worked so well together. But the anomalies in the fingerprints persuaded Fox too. By his account, they seemed to “jump off the page,” and he agreed that those differences suggested a third, very distinct form of life.

Still, Woese and Fox both knew that convincing other scientists of such an epochal discovery would be difficult. More data were needed. So the Woese lab went back to work, with Balch’s methodology and help, on culturing and fingerprinting still another methanogen. Woese and his colleagues worked quietly, for the time being. By the end of 1976, they had five additional genetic catalogs from five more methanogenic microbes, all quite different from one another but sharing signs of a much greater, much deeper, and shared difference from anything else known to exist.

## [21]

Bacteria are versatile and diverse. That’s an understatement. Widespread—another understatement. They are hard to categorize, hard to identify, hard to sort into related groups, as even Stanier and van Niel finally admitted. They are nearly ubiquitous across most parts of Earth’s expanse, in both natural and human-made environments, floating through the air, coating surfaces everywhere, awash in the oceans, even present in rocks deep underground. Your skin as I’ve said is covered with them. Your gut is teeming. Your human cells may be outnumbered by them at a three-to-one ratio in your body. Bacteria live also in mudholes and hot springs and puddles and deserts, atop mountains, deep in mines and caves, on the tabletops at your favorite restaurant, and in the mouths of you and your dog.

A species called Bacillus infernus has been cultured from core samples of Triassic siltstone, buried strata at least 140 million years old, drilled up from almost two miles beneath eastern Virginia. Under the Pacific Ocean, 35,755 feet deep in the Mariana Trench, lie sediments that have also yielded living bacteria. In Antarctica, a body of water known as Subglacial Lake Whillans, lidded by half a mile’s thickness of ice and supercooled to just below zero, harbors a robust community of bacteria. They thrive there in the darkness and cold, eating sulphur and iron compounds from crushed rock.

Then again, some like it hot. Those are called thermophiles. Among the most famous of thermophilic bacteria is Thermus aquaticus, first cultured from a sample collected in Yellowstone National Park by the microbiologist Thomas Brock and a student, Hudson Freeze, in 1966. Brock and Freeze had found it in a steaming, multicolored pool called Mushroom Spring, in Yellowstone’s Norris Geyser Basin, at a temperature of about 156 degrees Fahrenheit. Functioning in such heat, Thermus aquaticus contains a specialized enzyme for copying its DNA, one that performs well at high temperatures, which became a key element in the polymerase chain reaction technique for amplifying DNA. That technique, widely useful in many aspects of genetic research and biotech engineering, earned its chief developer (but not Thomas Brock) a Nobel Prize.

Other heat-loving bacteria can be found around hydrothermal vents on the sea bottom, where they help anchor the food chains, producing their own organic material from dissolved sulfur compounds vented out with the hot water, and being fed upon by little crustaceans and other animals. A giant tube worm, one of those gaudy red creatures that waggle around such vents, with no mouth, no digestive tract, gets its nutrition from bacteria growing within its tissues.

By one estimate, the total mass of bacteria exceeds the total mass of all plants and animals on Earth. They have been around, in one form or another, for at least three and a half billion years, strongly affecting the biochemical conditions in which most other living creatures have evolved. That we don’t see bacteria is simply because our eyes are not calibrated to the appropriate scale. There may be more than a billion bacterial cells in an average ounce of soil, and five million in a teaspoon of fresh water, but we can’t hear their crackle or their fizz. A single kind of marine bacteria known as Prochlorococcus marinus, which drifts free in the world’s tropical oceans and photosynthesizes like a plant, may be the most abundant creature on Earth. One source places its standing population at three octillion individuals, a number that looks like this: 3,000,000,000,000,000,000,000,000,000.

They vary in shape and in size—interestingly in shape, drastically in size. A bacterial cell, on average, is about one-tenth as big as an animal cell. At the upper end of the range is Thiomargarita namibiensis, an odd thing discovered on the sea floor near Namibia, its cells ballooning up to three-quarters of a millimeter in diameter, stuffed with pearly globules of sulfur. At the lower end of the range is Mycoplasma hominis, a tiny bacterium with a tiny genome and no cell wall, which manages nonetheless to invade human cells and cause urogenital infections.

Bacterial shapes, as I’ve mentioned, range through rods, spheres, filaments, and spirals, with variations that in some cases represent adaptations for movement or penetration. It turns out that their geometries, notwithstanding the efforts and convictions of Ferdinand Cohn, are unreliable guides to their phylogeny. Shape can be adaptive, but adaptations can be convergent as well as ancestral. Roundness may be good as a hedge against desiccation. Elongation as a rod or filament seems to help with swimming, and a flagella definitely does. Filamentous bacteria that are star shaped in cross section, recently discovered in a wonderfully named substance called “mine-slime,” deep in a South African platinum mine, may profit from all their surface area by way of enhanced absorption in nutrient-poor environments. The twisting motion of spirochetes, such as the ones that cause syphilis and Lyme disease, evidently allows them to wiggle through obstacles that other bacteria can’t easily cross, such as human organ linings, mucous membranes, and the barrier between our circulatory system and our central nervous system—a fateful degree of access. Even the less dynamic shapes, the short rods known as bacilli, the spheres known as cocci, and the rods slightly curved like commas, serve well enough the bacteria responsible for a long list of diseases: anthrax, pneumonia, cholera, dysentery, hemoglobinuria, blepharitis, strep throat, scarlet fever, and acne, among others.

Although many bacteria live as solitary cells, taking their chances and meeting their needs independently, others aggregate into pairs, clusters, little scrums, chains, and colonies. The coccoid cells of Neisseria gonorrhoeae, which cause gonorrhea, lump together by twos, forming bilobed units resembling coffee beans. The genus Staphylococcus gets its name from Greek words for “granule” (kókkos, the spheroid aspect) and “a bunch of grapes” (staphylè), because staph cells tend to bunch. Most of the forty staph species are harmless, but Staphylococcus aureus can inflict skin infections, sinus infections, wound infections, blood infections, meningitis, toxic shock syndrome, plus other nasty conditions, and if you’re so unlucky as to pick up a dose of those little grapes in one of their antibiotic-resistant forms, such as MRSA, a monstrous product of horizontal gene transfer (as I’ve mentioned, and to which I’ll return), you could be in a world of hurt. Cells of Streptococcus species, including those that cause impetigo and rheumatic fever, stick together like beads on a chain.

Bacteria can also form stubborn, complex films on certain surfaces—the rocks of a sea floor, the glass wall of an aquarium, the metal ball of your new artificial hip—where they may cooperate together in exuding a slimy extracellular substance that helps nurture them collectively, maintain the stability of their little environment, serve as a sort of communications matrix among them, and even protect them from antibiotics. These living slicks, known as biofilms, can be thinner than tissue paper or as thick as a good dump of snow, and may incorporate multiple species. The little rods of Acinetobacter baumannii are infamous for their ability to lay down persistent biofilms on dry, seemingly clean surfaces in hospitals.

Cyanobacteria, including that monumentally abundant Prochlorococcus, convert light to energy and deliver, as byproduct, a large share of Earth’s free atmospheric oxygen. Purple bacteria photosynthesize too, but do it by drawing upon sulfur or hydrogen instead of water as fuel for the process, and they don’t produce oxygen. Lithotrophic bacteria, the rock eaters, deriving their energy from iron, sulfur, and other inorganic compounds, exist in more ingenious variants than you care to know. Japanese researchers have recently discovered a new bacterium, Ideonella sakaiensis, that digests plastic. Certain enterprising ocean bacteria, such as Marinobacter salarius, have risen to the challenge of degrading hydrocarbons from the Deepwater Horizon oil spill. Other bacteria are quite capable, in the presence of oxygen or without it, of feasting on garbage, sewage, various inorganic compounds, plants, fungi, and animal tissue, including human flesh. Lactic acid bacteria, which may be rod shaped or spherical, turn up in milk products, busy at their task of carbohydrate fermentation and resistant to the acid they create. Many of them also like beer.

Not all such particulars were known to Carl Woese in 1977 as he examined the fingerprints from his first few methanogens. But the vast scope, ubiquity, and multifariousness of bacteria certainly were. The terrain of bacteriology was known even better to Ralph Wolfe, who had trained in the classic fundamentals under van Niel and others. Woese’s reaction to his own preliminary results must have seemed all the more radical, then, all the more shocking, as he shared it not just with George Fox and members of his own lab but also with Wolfe, just after they repeated the rRNA analysis of delta H, the first methanogen. “Carl’s voice was full of disbelief,” Wolfe wrote in a memoir, “when he said, ‘Wolfe, these things aren’t even bacteria.’”

## [22]

Ralph Wolfe told me the same story, with some elaboration, thirty-nine years later when I called on him in Urbana. By then, he was an emeritus professor of microbiology, ninety-three years old, a frail and slender gentleman with a quick smile, still maintaining his office and coming to it, as though retirement were not an entirely satisfying option. On the wall behind his desk hung a replica of Alessandro Volta’s pistola, a gunlike device invented by Volta in the late 1770s for testing the flammability of swamp gases, including methane. On the desk itself were papers and books and a computer.

Woese’s lab back in the day had been in Morrill Hall, on South Goodwin Avenue, and Wolfe’s was in an adjacent building, connected by a walkway. Woese would occasionally trundle over on various business. “He came down the hall and happened to see me,” Wolfe recalled, “and says, ‘Wolfe, these things aren’t even bacteria!’” Wolfe laughed gently and, for my benefit, continued reenacting the scene.

“‘Of course they are, Carl.’” They look like bacteria in the microscope, Wolfe had told him. But Woese wasn’t using a microscope. He never did. He was using ribosomal RNA fingerprints.

“‘Well, they’re not related to anything I’ve seen.’” Coming back to the present, Wolfe said: “That was the pivotal statement that changed everything.”

## [23]

We went into fast-forward mode,” Woese recalled in his account of these events. By the end of 1976, his team had done fingerprints and catalogs on five additional methanogens, with more in the pipeline. And sure enough, he wrote, none of the new catalogs was prokaryotic, not in the prevailing sense of that word, which meant bacteria and only bacteria. None of the organisms was eukaryotic, either. But “they were all of a kind!”—a third kind, something else, something anomalous, something hitherto unsuspected to exist. Woese started thinking that he would need to declare a new kingdom of life—create a new name, invent a huge new category—to recognize their uniqueness and contain them. It wasn’t really a new kingdom, of course. It was a newly discovered natural grouping of life-forms, which had existed apart for a long time, unrecognized, and which might be called a “kingdom” or an “urkingdom” or a “domain,” according to preferred human convention.

Woese believed that this discovery, still unannounced, offered “a rare opportunity to put the theory of evolution to serious predictive test.” He meant Darwin’s theory of evolution, as opposed to any others—the one that recognized hereditary continuity plus a degree of random variation over long stretches of time, and explained the shaping of that variation, to yield adaptation and diversity, mainly by way of natural selection. If Woese’s preliminary findings were correct, he noted, those findings should serve as a guide for predicting roughly what further data and discoveries would appear. From the premise that 16S rRNA represented a very slow-ticking molecular clock, with a minimum of selected variation, he deduced that his newly found kingdom must represent a very old division. Very old—having originated near the beginning of cellular life, maybe three and a half billion years ago. Now he would try to sketch its boundaries and its characteristics. As he and his team added more microbes to its membership—more methanogens and maybe other creatures too, each known by its catalog of RNA fragments—Woese expected two things: that this unnamed kingdom would remain dramatically distinct from the rest of the living world and that it would nonetheless encompass great diversity. “Testing these two main evolutionary predictions,” he wrote, “drove our work from that point on.”


Three domains and (within the eukaryotes) four kingdoms, four types of cell.

In August the team published a carefully limited paper, just a hint of what was coming, in the Journal of Molecular Evolution, the same journal at which Emile Zuckerkandl continued to serve as editor. It was a logical match of subject and outlet because Zuckerkandl, back in his days as Linus Pauling’s sidekick, had helped articulate the very premise that Carl Woese was now putting dramatically to use: that the branching of lineages “should in principle be definable in terms of molecular information alone.” The molecular information at issue in this case consisted of ribosomal RNA sequences from the first two methanogens Woese’s team had characterized. One of those methanogens was a strain of M. ruminantium, isolated from rumen fluid (from the paunch of a cow) donated by a friendly contact in the university’s Department of Dairy Science. The other was delta H, the conveniently nicknamed strain of the fourteen-syllable monstrosity, M. thermoautotrophicum, known to live at high temperatures and metabolize hydrogen. I asked Ralph Wolfe where they had gotten their starter sample of that exotic beast, delta H.

“It was isolated here from the sewage.” More specifically, from a sewage sludge digester.

“In Urbana?”

“Yeah.”

The first author on this discreet paper was Bill Balch, Wolfe’s graduate student, who had earned his authorship priority by developing the sealed-tube technique of growing and labeling methanogens. “It was because of that technique,” Wolfe told me, “that we could now do these experiments with Carl. Because everything was sealed, and you could now inject the P-32 into the culture.” P-32, remember, was the radioactive phosphorus. “Whereas the previous techniques, you had to keep opening the stopper and flushing it out, and it would have been a radioactive nightmare to do it that way.” Balch’s system allowed for injecting the P-32 by syringe through the black rubber stopper. Balch grew the microbes, George Fox extracted the RNA, and Woese’s trusted lab technician at the time, a young woman named Linda Magrum (she had replaced the earlier Linda in that role, Linda Bonen), prepared the fingerprint films for Woese to analyze. All three of them, plus Ralph Wolfe himself, appeared as coauthors, with Woese’s name last, reflecting his role as senior author. Besides describing the methodology, this paper noted drily that the two methanogens didn’t look much like “typical” bacteria. It mentioned that the divergence might represent “the most ancient phylogenetic event yet detected”—a big claim, vague enough as stated to pass almost unnoticed.

In October the team published a second paper, in a more far-reaching journal, the Proceedings of the National Academy of Sciences (known as PNAS). This time George Fox was first author, and the data covered ten species of methanogen, each one assessed for similarity to the other nine and to three species of what the authors still cautiously called “typical bacteria.” Fox had created a simple measurement system by which the catalog of one microbe could be compared with the catalog of another, yielding a decimal number—a coefficient—representing degree of similarity. Comparing each of these thirteen microbes with all the others gave an overall picture of which were how closely similar to which others. The data could be arranged in a rectangular table, names down the left margin, names again across the top, numbers at each cross point, as in a chart showing the various mileage distances between all pairs in a list of cities. Instead of mileage: a similarity coefficient. From those numbers, and the premise that similarity reflected relatedness, Fox generated a dendrogram, a branching figure, showing nodes of divergence between major lineages and a branch for each organism. Although they printed this dendrogram sideways—like a bracket for the NCAA basketball tournament—rather than vertically, it was, in fact, a tree: the first of the new trees of life in the era of Carl Woese. There would be many more.

This one showed the “typical bacteria” occupying one major limb. The ten methanogens all branched from a second major limb. “These organisms,” said the paper, “appear to be only distantly related to typical bacteria.” Again the five authors were saying less than what they believed. The phrase “typical bacteria” was an interim delicacy that would soon disappear.

A third paper, the most bold and dramatic, appeared in PNAS a month later under the authorship of Woese and Fox alone. Its title hinted only obliquely at its intent: to reorganize “the primary kingdoms” of life. Again using Fox’s similarity coefficients, it compared methanogens against one another and against “typical bacteria,” and each of those also against several eukaryotic organisms, including a plant and a fungus. Its conclusion was radical: there are three major limbs on the tree of life, not two. The prokaryote-eukaryote dichotomy, as proposed by Stanier and van Niel, as generally accepted throughout biology, is invalid. “There exists a third kingdom,” Woese and Fox wrote, and it includes—but may not be limited to—the methanogens. It isn’t the bacteria, and it isn’t the eukaryotes, they explained. It’s a separate form of life.

The two authors gave their kingdom a tentative name: archaebacteria. Archae- seemed apt, suggesting archaic, because the methanogens appeared so ancient, and their metabolism might have been well suited to early environments on Earth, about four billion years ago, before the onset of an oxygen-rich atmosphere. Woese had made that very point in an interview with the Washington Post. “These organisms love an atmosphere of hydrogen and carbon dioxide,” he said (or at least, so he was quoted). “Just like the primitive earth was thought to be,” he said, adding, “No oxygen and very warm.” But the other half of that compound label, archaebacteria, tended to blur the central point of the discovery: that, as Woese had announced to Wolfe, these things aren’t even bacterial forms of life. They’re quite different. Wolfe himself told Woese that archaebacteria was a terrible choice. If they’re not bacteria, why retain that word at all? The provisional name stuck for about a dozen years, before being emended to something better, something that stood by itself: the archaea.

## [24]

George Fox was no longer a rangy young man when I sat with him in a nondescript pizza parlor near the campus in Urbana, after the opening session of a Carl Woese memorial symposium, and watched him eat a nondescript little pizza. Fox is a man who prefers simple, plain food, and he had cringed when I ordered pepperoni and mushrooms on my own. At age sixty-nine, he carried the full body and slight jowls of a lifetime spent in laboratories and classrooms; wire-rim spectacles had replaced the dark horn-rimmed glasses he had worn in the 1970s photos, and his brown hair was graying at the temples, but his eyes still shined brightly blue as he recalled the days and years with Woese. Now a professor at the University of Houston, Fox had flown up for the Woese meeting, which was hosted by the Carl R. Woese Institute for Genomic Biology (its name reflecting the fact that Woese has become a venerated brand at the University of Illinois). Fox would give one of the invited talks.

He had spent his academic career at three institutions: Houston, for almost three decades; preceded by Illinois, as a postdoc with Woese; and before that it was Syracuse University, as an undergraduate and PhD student. The circumstances of Fox’s arrival in Urbana were haphazard, beginning from a coincidence in Syracuse, where Woese himself grew up. There at the university, Fox belonged to a professional engineering fraternity, Theta Tau, of which Carl Woese’s father—also named Carl Woese—was a founder, and so Fox was required to know the name. As he shifted interest from chemical engineering to theoretical biology, he noticed and became fascinated by some of the early work of Carl Woese the son. In particular, there was a paper on what Woese called a “ratchet” mechanism of protein production by ribosomes—a risky proposal, a wild and interesting idea (later proven wrong in its details), published in 1970. So Fox wrote to this ratchet guy asking for a postdoc fellowship, and Woese seemed to see the Syracuse connection as karma. He had a position to fill, yes, with the departure of Mitch Sogin, the ultimate handyman grad student, and he offered that to Fox.

“We did not discuss salary,” Fox said over his pizza and Coke. “He never sent me a letter offering the position. It was all completely verbal.” On such assurance, Fox got married and showed up in Urbana that autumn with his wife. Arriving unannounced, he encountered a man at the lab door, an unprepossessing figure in jeans and a drab shirt, with a chain holding a huge bunch of keys. “He looked like the goddamn janitor.” Fox gave his name and prepared to talk his way in. “No!? Welcome!” It was Woese.

“He sat me down in his office and …” Fox hesitated. “You got a piece of paper?” On a yellow sheet from my legal pad, he began sketching the layout of the lab. He drew a long rectangle and subdivided it. There were three major rooms, he explained, and the middle room, here, held the light table, where Carl usually worked. Linda Magrum and Ken Luehrsen were here, in the left room. Over here on the right side of the center room was Carl’s little personal office and the electrophoresis room. The radiation room and the darkroom were across the hall, and then storage, three more spaces barely bigger than closets. Woese gave Fox a table in his office, Fox said, with a door that stayed open, “so he could see me.” Like the young Luehrsen, only more so, as a postdoc, Fox was on probation.

At the beginning, Woese assigned him to assembling sequences from 5S rRNA, the shortest and least informative of the ribosomal RNA molecules, as a way of getting up to speed on what the lab was doing. That project yielded some unexpected results, impelling Woese to try to make Fox an experimentalist. But it wasn’t his forte, and he knew that. He wanted to do the sort of “theoretical stuff,” the deep evolutionary analysis of molecular data—what would now be called bioinformatics—that Woese himself did. Reading the code, drawing conclusions that went back three billion years and more. Woese, on the other hand, wanted him to generate data. “I was under a lot of pressure,” Fox recalled—the pressure of Woese’s expectations versus his own interests and skills. “What I had to do was, every other day, come up with a novel insight, so that he would continue to allow me to work on the sequence comparison project.” Failing that impossible standard, he was banished back to the lab, set to the tasks of growing hot cells and extracting their ribosomal RNA. But Fox continued, in flashes, to show his value to Woese as a thinker. Gradually he proved himself, not just sufficiently to work on sequence comparisons but well enough to become Woese’s trusted partner, as well as the sole coauthor on the culminating paper in 1977, with its announcement of a third kingdom of life.

## [25]

Wondering how that announcement was greeted by the scientific community at the time, I had put the question to Ralph Wolfe, several months before the pizza with George Fox.

“It was a disaster,” Wolfe said mildly. Then he explained, with the sympathy of friendship, why Woese’s declaration of a third kingdom—the substance of the claim, and the manner in which Woese made it—had sounded discordantly to many of their peers. The crux of the problem was a press release.

Woese’s lab had been supported by the National Science Foundation and the National Aeronautics and Space Administration, the latter under its exobiology program (devoted to extraterrestrial biology, in case there is any), presumably because grant administrators felt that his research on early evolution might help illuminate the question of life on other planets. As the first PNAS paper in the methanogens-aren’t-bacteria series moved toward publication, Woese acceded to a suggestion from the federal agencies and allowed a public announcement of his findings from Washington, rather than just letting the article drop in the journal’s November issue and speak for itself—which was how science, in those days, was customarily done. Ralph Wolfe knew nothing about this, despite his close connection with the work, until one day when a mutual acquaintance let slip that the press release would appear tomorrow. “What press release?” Wolfe asked.

The cat was out. It was an indelicate situation. “A few minutes later,” Wolfe told me, “Carl was in my office, explaining.”

Wolfe showed no dudgeon as he recounted this. The human comedy is various, not always funny; Woese’s lapse was just a miscommunication between friends, a misstep by a colleague he held in high regard. To understand what went wrong, you had to consider an insult Woese had suffered years earlier, a hurt he had carried long afterward. “He presented a paper in Paris,” Wolfe said. It was on the ratchet model, the same clever but incorrect idea that later caught George Fox’s interest. Woese had conceived this brainstorm—a conceptual construct for how ribosomes work in manufacturing proteins—and called it a Reciprocating Ratchet Mechanism, by which RNA cranks through the ribosome structure, adding amino acids to the protein chain, a notch forward, and then a reload, and then another notch forward, but never a notch back.

“He didn’t present any evidence for it,” Wolfe said. “He just presented this as a concept.” The audience at the Paris meeting may have included luminaries such as Jacques Monod, François Jacob, and Francis Crick, whom he knew a bit better than the others. “It was the last paper before lunch,” Wolfe said, “and nobody asked any questions. They all got up, and left, and went to lunch. And this hurt Carl. It was almost a mortal wound. He was just so offended by the behavior of these scientists. He told me that ‘I resolve next time they will not ignore me.’ And so this was the rationale behind his press release.”

The press release went out from Washington, presumably with an embargo to the date of journal publication. On November 2, 1977, the third kingdom became an open topic for all comers. The following day, based on that alert and three hours with Woese in his office, a reporter for the Times told the story on page 1, beneath the photo I’ve already mentioned—of Woese with his Adidas on a messy desk—and a headline emphasizing the ancientness theme: “Scientists Discover a Form of Life That Predates Higher Organisms.” The article, by a veteran Times man named Richard D. Lyons, began:

Scientists studying the evolution of primitive organisms reported today the existence of a separate form of life that is hard to find in nature. They described it as a “third kingdom” of living material, composed of ancestral cells that abhor oxygen, digest carbon dioxide and produce methane.

That was relatively accurate compared with coverage in some other news outlets. The Washington Post did less well than the Times, reporting that Woese claimed to have found the “first form of life on earth,” which suggested that a dawn organism, the very earliest living creature, self-assembled somehow about four billion years ago, had survived to occupy sewage in twentieth-century Urbana. Wrong. The Chicago Tribune was worse still, proposing that Methanobacterium thermoautotrophicum (misspelled) had left no fossil record because it “evolved and went into hiding” at a time before rocks had yet formed. Which rocks? “Utter nonsense,” Wolfe said. The Tribune story even carried a dizzy headline asserting “Martianlike Bugs May Be Oldest Life.” And from there the coverage spooled outward, via United Press International and other echo chambers, to small-town papers such as the Lebanon Daily News in Pennsylvania, under similar headlines tooting about “Oldest Life Form” rather than the distinctness between methanogens and all (“typical”) bacteria. At very least, the stories bruiting “Oldest Life Form” were missing an essential point presented by Woese and Fox. A headline about “Weirdest Life Form” might have captured that better.

The problem, according to Ralph Wolfe, was not just announcing scientific results by press release but also that Carl Woese himself lacked facility as a verbal explainer. He had never developed the skills to give a good lecture. He stood before audiences—when he did so at all, which wasn’t often—and thought deeply, groped for words, and started and stopped, generally failing to inspire or persuade. Then suddenly that November of 1977, for a very few days, he had the world’s attention.

“When reporters called him up and tried to find out what this was all about,” Wolfe told me, “he couldn’t communicate with them. Because they didn’t understand his vocabulary. Finally, he said, ‘This is a third form of life.’ Well, wow! Rockets took off, and they wrote the most unscientific nonsense you can imagine.” The press-release approach backfired, the popular news accounts overshadowed the careful PNAS paper, and many scientists who didn’t know Woese concluded, according to Wolfe, that “he was a nut.”

Wolfe himself heard from colleagues immediately. Among his phone calls on the morning of November 3, 1977, “the most civil and free of four-letter words” was from Salvador Luria, one of the early giants of molecular biology, a Nobel Prize winner in 1969 and a professor there at Illinois during Wolfe’s earlier years, who called now from the Massachusetts Institute of Technology (MIT), saying: “Ralph, you must dissociate yourself from this nonsense, or you’re going to ruin your career.” Luria had seen the newspaper coverage but not yet read the PNAS article, with the supporting data, to which Wolfe referred him. He never called back. But the broader damage was done. After Luria’s call and others, Wolfe recollected in his memoir, “I wanted to crawl under something and hide.”

To me, he added: “We had a whole bunch of calls, all negative, people outraged at this nonsense. The scientific community just totally rejected the thing. As a result, this whole concept was set back by at least a decade or fifteen years.” Wolfe himself felt badly burned by the events, his professional reputation in peril. There arose a wall of resistance—cast up by visceral objection to science by press release—against recognizing the archaea as a separate form of life. “Of course, Carl was very bitter all through the eighties and well into the nineties,” Wolfe said. “He was bitter that the scientific community rejected his third form. His phylogeny and taxonomy.” As it had been for Stanier and van Niel, and still earlier for Ferdinand Cohn, bacterial taxonomy was a hot issue again. This time the evidence was molecular, and the deeper story was of evolution on its broadest scale.

## [26]

It’s hard to know in retrospect, and perhaps tempting to overestimate, just how severely Carl Woese was doubted, dismissed, and ridiculed during the decade following 1977. Certainly there was some of that, especially in America. But the resistance to his big claim softened somewhat after still another article, coauthored again with Ralph Wolfe and Bill Balch, offered many kinds of evidence (in addition to the 16S rRNA data) for considering methanogens a separate form of life. And in Germany, on the other hand, his idea of the newfound kingdom met a warm reception.

Researchers there—three in particular—had been developing some parallel observations. The first was Otto Kandler, a botanist and microbiologist from Munich, with an interest in cell walls, who happened to visit Urbana earlier in 1977, before the papers were published, and met Woese through Ralph Wolfe. “Ralph marched him into my office to hear the official word from George and myself,” according to Woese’s later memory of encountering Kandler. “I think he smiled.” With a smile or not, Otto Kandler easily accepted the premise that methanogens were profoundly unique, because he had suspected it himself. His own work had shown him something even Woese and Wolfe didn’t know: that the cell walls of at least one methanogen were starkly anomalous. They contained no peptidoglycan. Remember that stuff, peptidoglycan—the latticework molecule, a strengthener of cell walls, that Stanier and van Niel had cited as one of the defining characters of all prokaryotes? It didn’t exist, zero, in the cell walls of a certain methanogen Kandler was studying. Furthermore, he told Woese, it seemed absent also from some other untypical bacteria, which lived amid high concentrations of salt. They were known, for that affinity, as halophiles. Salt lovers.

The tip from Kandler about anomalous cell walls triggered a memory in George Fox. He had once been taught, in a microbiology course, that all bacteria have peptidoglycan walls—all except the extreme halophiles. Reminded of that by the German, Fox went to the library to verify it, and, in the process, he found another clue to the defining characters for inclusion in this third kingdom. Here we get technical again, but I’ll keep it simple: weird lipids.

Lipids are a group of molecules that includes fats, fatty acids, waxes, some vitamins, cholesterol, and other substances useful in living creatures for purposes such as energy storage, biochemical signaling, and as the structural basis of membranes. Fox, rummaging in his library, learned that halophiles contain lipids unlike those in other bacteria. They were structured differently, with radically different chemical bonds. Carl Woese now had another omigod moment: Omigod, these salt lovers are full of weird lipids, just like our methanogen. The fact of such weird lipids in halophiles had been reported by other researchers a dozen years earlier—as Fox found in the library—but no one had drawn any conclusions. It was merely a little anomaly. But for Woese, in his ferment of discovery, it clicked into the larger pattern. “In my whole career I had never paid attention to lipids, and here we were with lipids on the brain!”

And not just the lipids he found in halophiles. Fox also turned up the fact that two other kinds of extremity-loving bugs, known by their genus names as Thermoplasma and Sulfolobus, also had weird lipids of the same sort. Those two groups preferred environments that were very hot and very acidic, such as hot springs in areas of volcanic activity. In the technical lingo, they were thermophilic and acidophilic. Perverse little beasts, by our standards. Both had recently been isolated—one from a coal refuse pile, the other from a hot spring in Yellowstone—and characterized in the lab of Thomas Brock, the codiscoverer of Thermus aquaticus. Alerted to the weird-lipids connection by Fox, Woese got hold of samples and began trying to grow them and catalog them.


The three domains of life: Bacteria, Archaea, Eukaryotes.

In light of all this, Woese suddenly became very keen to fingerprint some salt lovers. He reckoned that “if unusual cell walls meant anything, perhaps the extreme halophiles would turn out to be members of our new ‘far out’ group.” George Fox, by this time, had left for the University of Houston. With Fox gone and his other lab people already busy, Woese couldn’t wait for another student or collaborator to come along, so he started the wet work himself. Fortunately for him, growing halophiles is relatively easy. “I donned my acid-eaten lab coat (which had hung on the back of my office door for over a decade) and went back to the bench.” He grew the cultures in quantity from samples sent by a colleague, tagged them with P-32, and turned them over to Ken Luehrsen for the dicier next step: extracting and purifying radioactive RNA. Then from Luehrsen the stuff went to Linda Magrum—“our trusty Linda,” Woese called her—for separation by electrophoresis and burning the films. Within a few months, they had their first catalog from a halophile. “It didn’t disappoint,” Woese wrote. It was another strange thing: not a bacterium after all, but a member of the archaea.

So much for the halophiles. He turned back to the thermophilic acidophiles. When his team finished fingerprinting the coal-refuse creature, Woese sent a manuscript to the journal Nature, presenting the new ribosomal RNA catalog and making a case that this creature too belonged among the archaea. Nature rejected the paper, with a return letter that essentially said: “Who cares?”

## [27]

The three Germans cared—not just Otto Kandler, who became a great pal to Woese, but also Wolfram Zillig, an eminent biologist who directed the Max Planck Institute for Biochemistry, in Munich, and his younger associate, Karl Stetter, formerly a student of Kandler’s. After meeting Woese and hearing firsthand about his evidence and his radical idea, Kandler carried the news back to Munich, where he shared it with Stetter, then still a junior researcher. Stetter was straddling two roles—teaching in Kandler’s institute at the University of Munich, running a lab within Zillig’s operation, commuting between them daily—and he brought Kandler’s news from America across town. When he delivered his thirdhand account in a Friday seminar at the Max Planck Institute, Wolfram Zillig’s initial reaction was cold. Zillig, born in 1925, was just old enough to remember Nazism and the war from the perspective of a soldier-aged young man. As the story comes from Karl Stetter, recounted to Jan Sapp decades later, Zillig in 1977 reacted sourly to Kandler’s scuttlebutt about Woese’s third kingdom of life. “A Third Reich?” he snapped. “We had enough of the Third Reich!”

But Zillig’s resistance fell and his interest rose when he heard, a few months later, that Woese possessed data on the uniqueness of halophiles that nicely paralleled his data on the uniqueness of the methanogens. Zillig and Stetter then reset their own research efforts, which involved something called RNA polymerase (the enzyme that helps turn DNA code into messenger RNA), to see whether anomalies in that molecule among salt-loving “bacteria,” among heat-loving and acid-loving “bacteria,” and among methane-producing “bacteria”—anomalies that might set them apart from typical bacteria—matched the drastic anomalies Woese was finding by his own method. They did match. So maybe these microbes weren’t bacteria after all.

Derided in the United States, controversial at best, Woese was becoming a scientific lion in Germany, at least in those erudite circles where researchers studied the molecular biology of microbes. In 1978 Kandler invited him to a major congress of microbiologists in Munich. Woese declined. In a polite but cranky letter, he groused that the National Science Foundation and NASA were being stingy with him on grant funds while enjoying the considerable publicity from his work, and also that, quite apart from the costs, travel interrupted his research. Interruptions he found annoying. He was a driven man—toward results, not companionship. But the following year, Kandler tried again, and this time Woese accepted. His hosts paid the way. They treated him well. They asked only that he deliver a keynote lecture at another microbiology conference and then a seminar at Zillig’s institute. On the night of a festive dinner, in a great hall at the University of Munich, Kandler laid on a brass section from a local choir. They gave Woese a fanfare of trumpets. Not many molecular phylogeneticists ever get that level of jazzy appreciation. It melted his frosty rime.

Two years later, his German friends organized another meeting in Munich, this time an international conference—though they called it a workshop, suggesting informality and collaboration—devoted entirely to the archaea. It was the first such conference ever, giving the third kingdom a new measure of recognition. The attendance was relatively small, about sixty people, but included researchers from Japan, the United States, Canada, Great Britain, the Netherlands, and Switzerland, as well as the Federal Republic of Germany (West Germany), where the archaea were now big; and its program encompassed a wide range of topics and approaches. Ralph Wolfe came. So did Ford Doolittle, George Fox, and Bill Balch. Woese not only traveled to Munich again but also delivered the welcoming address—and he made that a substantive lecture, rich with ideas and provocations, not just a ceremonial greeting.

“We are about to embark on a scientific meeting of historic significance,” he told the group (as reported later in the proceedings, edited by Otto Kandler). What they shared, this assemblage of scientists, was their concept of the archaea, which “did not exist four years ago.” They had been working, in their respective labs, with “organisms that intuitively felt peculiar”: methanogens, halophiles, thermoacidophiles. These things had seemed idiosyncratic and unrelated. We had been slow to recognize their connectedness, their unity, Woese said, because the existing framework of bacterial taxonomy was so misleading in its overview and so wrong in its details.

“Generations of failure had discouraged the microbiologist about ever uncovering the natural relationships among the bacteria.” Here he was talking about the generations that had included Ferdinand Cohn, C. B. van Niel, and Roger Stanier. “With a few important exceptions, microbiologists were content to classify bacteria determinatively,” he added, alluding pointedly to Bergey’s Manual of Determinative Bacteriology, the authoritative handbook, and the cautious experts who had produced it for sixty years. The problem with that approach, Woese complained, was that it tried to understand bacteria only as static entities—items to be placed into categories of convenience. “Matters of their evolution became reserved for enjoyable but idle after-dinner speculation.” That’s what was missing from both microbiology and now molecular biology, he said: evolution.

Woese was casting down a gauntlet: telling some of the most brilliant and influential figures of late-twentieth-century biology—his friend Francis Crick, Crick’s colleague James Watson, the Nobel winners François Jacob and Jacques Monod and Max Delbrück and Salvador Luria, who had counseled Ralph Wolfe to stay away from Woese for the sake of his good reputation—that they were shallow, mechanistic thinkers with no curiosity about life’s history. That they were nothing but code breakers, riddle solvers, and engineers. The questions and answers offered now by the recognition of the archaea, he said, should go far to revivify evolutionary thinking, and “hopefully divert biology to some extent from its present course of technological adventurism.” By that odd phrase, “technological adventurism,” he seems to have meant not just high-tech molecular biology for its own sake, without regard for evolutionary questions, but also perhaps gambits in genetic manipulation. It was a condemnation so damning and prescient, this whole 1981 rant, that you might imagine he had foreseen gene patenting, the growth of the biotech industry, gene-editing therapies, preimplantation screening of human embryos, and full-on human germline engineering. He set this “technological adventurism” against “molecular evolutionary biology,” his ideal, but an unspoken phrase, which at that time would have seemed oxymoronic.

That’s the notable takeaway from his 1981 Munich talk: it reflects Carl Woese’s compulsion to dig ever deeper into the narrative of life. He was a man possessed by the most deep-diving curiosity. This work he was doing, this door he had opened, this journey he was on—it wasn’t just about the Archaea, a third kingdom. It was about the origins and history of the other two kingdoms also. How did they arise? How did they diverge from one another? How were each of the three related to the two others? Which came first? Why did just one of the three lineages lead onward to all visible, multicellular organisms—all animals, all plants, all fungi, ourselves—while the other two remained unicellular and microscopic, though still vastly abundant, diverse, and consequential? And what kind of creature, or process, or circumstance preceded them all? Where was the tree of life rooted?

Woese wasn’t interested just in this separate form of life he had chanced upon. He was interested in the whole story.

Immediately after the workshop, which had gone well and given its participants a sense of momentum for the archaea concept, Kandler and his wife took Woese and Wolfe on a larkish field trip. They drove south from Munich into the Bavarian Alps and climbed a modest but picturesque mountain, the Hohe Hiss, along a graded path. “Woese and especially Wolfe were not in top physical shape, but with some huffing and puffing, they reached the top,” according to Ralph Wolfe’s own self-mocking account. At the summit, Kandler’s wife took a photo of the three men, all of them sunlit and contented on a clear day. Wolfe and Kandler appear as what they are: middle-aged scientists, balding, amiable, savoring a day outdoors. To their right sits Woese, with a full beard, leonine hair, a sweater tied jauntily over his neck, a cup of champagne in his left hand, smiling an easy, full smile of triumph. He was fifty-two years old, at the height of his powers and fame, and looked like a man on his way to a Nobel Prize.

PART III

## [28]

The entrance of Lynn Margulis into this story occurred abruptly, with some fanfare, at a time when Carl Woese still labored in obscurity. Margulis was a forceful young woman from Chicago. Her role proved important because it brought new attention and credibility to a very strange old idea: the idea that living ghosts of other life-forms exist and perform functions inside our very own cells. Margulis, adopting an earlier term, called that idea endosymbiosis. It was the first recognized version of horizontal gene transfer. In these cases, rare but consequential, whole genomes of living organisms—not just individual genes or small clusters—had gone sideways and been captured within other organisms.

Margulis made her debut in March 1967 with a long paper in the Journal of Theoretical Biology, the same journal that had carried Zuckerkandl and Pauling’s influential 1965 article on the molecular clock. This paper was much different. Its author was no canonized scientist like Pauling, and its assertions were peculiar, to say the least. Put more bluntly: it was radical, startling, and ambitious, proposing to rewrite two billion years of evolutionary history. It included some cartoonish illustrative figures, funny little pencil-line drawings of cellular shapes, and virtually no quantitative data. According to one account, it had been rejected by “fifteen or so” other journals before a daring editor at JTB accepted it. Once published, though, the Margulis paper provoked a robust response. Requests for reprints (a measure of interest, back in those slow-moving days before online access to journals, when scientists mailed one another their articles) poured in. It was titled “On the Origin of Mitosing Cells.”

That was a quiet phrase for a huge subject, though the title’s echoes of Darwin’s On the Origin of Species suggest the loud aspirations of the paper’s author. Never short of confidence, she was twenty-nine years old at that time, an adjunct assistant professor at Boston University, and a single mother raising two boys. She had been married as a teenager to a flashy young astronomer and, for the moment, was still keeping his surname. Her authorship on the paper read: Lynn Sagan. Later, she would be famous—venerated by some, dismissed and disparaged by others, including Carl Woese—under the surname of her second husband, Thomas N. Margulis. But to many of those who knew her, she was always and informally: Lynn.

The phrase “mitosing cells” is another way of saying eukaryotic cells, the ones with nuclei and other complex internal structures, the ones that compose all animals and plants and fungi (as well as some other intricate life-forms, less familiar because they’re microscopic). “Mitosing” refers to mitosis, of course, the phase in eukaryotic cell replication at which the chromosomes of the nucleus duplicate, then split apart into two bundles within two new nuclei, as a prelude to the cell fissioning into two complete new cells, each with an identical set of chromosomes. You learned about it in high school biology, not long before you dissected the poor frog. Mitosis is taught along with meiosis, the yang to its yin. Mitosis occurs during ordinary cell division, whereas meiosis constitutes “reduction division,” yielding the specialized sex cells known as gametes (eggs and sperm in an animal, eggs and pollen in a flowering plant). Meiosis in an animal yields four new cells, not two, after two divisions, not one, each resulting cell reduced to a half share of chromosomes. Later, sperm will meet egg, and, bingo, the full measure will be restored. It’s a little hard to remember which of those terms is which, I concede, but here’s my mnemonic: meiosis is reduction division because its spelling is reduced by the loss of the t in mitosis. Helpful? Granted, that leaves the inconvenient fact of meiosis containing the addition, not reduction, of an e. So, okay, never mind. But it works for me.

Mitosis defines all the cell divisions by which a single fertilized egg grows into a multicellular embryo and then an adult, and also by which worn-out cells are replaced with new cells. Your skin cells, for instance. The cells of a scar when a wound heals. The cells that replace your worn-out colon lining. Mitosis occurs everywhere in a body. Meiosis, by contrast, occurs only in the gonads. Lynn Sagan’s paper, though, wasn’t focused on mitosis as an ongoing process. The key word in her title was origin.

Her interest was the deep history, to the beginning, of eukaryotic cells. She quoted the statement from Roger Stanier and his textbook coauthors, declaring that the prokaryote-eukaryote distinction “probably represents the greatest single evolutionary discontinuity to be found in the present-day living world.” It was the biggest leap in the history of life—an Olympic long jump, a high jump, a backward slam dunk—forever reflected in the differences between bacteria and more complex organisms. She proposed to explain how that leap happened.

“This paper presents a theory,” Sagan wrote—a theory proposing that “the eukaryotic cell is the result of the evolution of ancient symbioses.” Symbiosis: the living together of two dissimilar organisms. She gave her theory the more specific name endosymbiosis, connoting one organism resident inside the cells of another and having become, over generations, a requisite part of the larger whole. Single-celled creatures had entered into other single-celled creatures, like food within stomachs, or like infections within hosts, and by happenstance and overlapping interests, at least a few such pairings had achieved lasting compatibility. So she proposed, anyway. The nested partners had grown to be mutually dependent, staying together as compound individuals and supplying each other with certain necessities. They had replicated—independently but still conjoined—passing that compoundment down as a hereditary condition. Eventually they were more than partners. They were a single new being. A new kind of cell.

No one could say, not in 1967, how many times such a fateful combining had occurred during the early eras of life, but it must have been very rare that the resultant amalgams survived for the long term. Later, there would be ways of addressing that question. Sagan left it open. Microscopy, which was her primary observational mode of research, couldn’t answer it.

The little entities on the inside of such cells had begun as bacteria, she argued. They had become organelles—working components of a new, composite whole, like the liver or spleen inside a human—with fancy names and distinct functions: mitochondria, chloroplasts, centrioles. Mitochondria are tiny bodies, of various shapes and sizes but found in all complex cells, that use oxygen and nutrients to produce the energy packets (molecules known as adenosine triphosphate, or ATP) for fueling metabolism. ATP molecules are carriers of usable energy, like rechargeable AA batteries; when the ATP breaks into smaller pieces, that energy is released for use. Mitochondria are factories that build (or recharge) ATP molecules. To drive the production, mitochondria respire, like aerobic bacteria. Chloroplasts are little particles—green, brown, or red—found in plant cells and some algae, that absorb solar energy and package it as sugars. They photosynthesize, like cyanobacteria. Centrioles are crucial too, but for now, I’ll skip the matter of how. All these components, Sagan wrote, resemble bacteria by no coincidence but rather for a very good reason: because they evolved from bacteria.

The bigger cells, within which the littler cells were subsumed, had been bacteria too (or possibly archaea, though that distinction didn’t exist at the time). They were the hosts for these endosymbioses. They had done the swallowing, the getting infected, the encompassing, and had offered their innards as habitat. The littler cells, instead of being digested or disgorged, took up residence and made themselves useful. The resulting compound individuals were eukaryotic cells.