“When a true genius appears in this world you may know him by this sign, that the dunces are all in confederacy against him.”
JONATHAN SWIFT
One day in Illinois, Carl Woese decided that he would like to understand how all of the organisms around him—the birds, trees, bugs, humans, and most important the microbes—were related. He had no good reason to believe he could do such a thing and little hope of much support in the endeavor. It was, at the time, impossible. As R. Y. Stanier said in 1970, speculation about evolutionary history was “a relatively harmless habit, like eating peanuts, unless it assumes the form of an obsession; then it becomes a vice.”1 To many, such evolutionary “speculation” was both unwarranted and intellectually dangerous—but, as would soon become clear, not to Carl Woese.
Carl Woese did not want to speculate. He would instead try to invent a method of seeing evolutionary history, a kind of microscope through which to visualize relationships among species. Carl Woese thought that with this new method he might delve into the history of life, and understand what no one had before, not only to test Margulis’s theories, but also to understand even broader patterns of evolutionary change. Mark Twain said that a man with a new idea is a crank until he succeeds. Twain does not need to state the related assertion, that a man with a new idea who never succeeds is forever a crank.
Carl Woese was serious about science from an early age. For him “there was no other way to cope with [his] world.” For Woese, even as a young boy, there seemed to be “two worlds, that of nature and that of people. The first was vast, wonderful, inscrutable, frightening, exciting, enticing, always moving, but nevertheless with an immutable consistency—it was a never-failing touchstone of truth. The world of people was the opposite: inconsistent, ever arbitrary, full of contradiction, anthropomorphizing, untrustworthy—almost devoid of truth.”* Woese was called to a quiet life of science and inquiry.2 He chose microbiology, but he could just as well have been an astronomer or a physicist. What was important was the search for truth.
Like Linnaeus, Leeuwenhoek, and many others, Carl Woese started his career at the periphery of his scientific field. Trained as a physicist for his undergraduate degree at Amherst College and then as a biophysicist for his doctorate at Yale University, he studied the physics of the cell—the bump and grind of microscopic machinery. He worked at General Electric and then the Pasteur Institute before being hired as a professor at the University of Illinois in 1964. At Illinois, he studied ribosomal RNA. Watson and Crick had decoded the language of DNA, but Woese was interested in translation—the process in the ribosome by which a specific piece of RNA is converted into protein and hence function. Woese perceived that at that moment, with DNA deciphered, it “was the time to start thinking about the evolution of the cell and its macromolecular componentry.”3 It was time to start thinking about the deep evolution of life. Woese felt that “a slight diversion” from his main research was in order so as to address these questions. That diversion would go on to dominate the next four decades of his life.
To make an evolutionary tree of all life, including microbial life, one would need to study an attribute of that life that changed slowly, and hence allow the differences between very old lineages to be compared. The building blocks that make up the ribosome—your ribosome, my ribosome, every ribosome—seemed to Woese like a good candidate. The ribosome is composed of protein and then also, and this is the key, a special kind of RNA: ribosomal RNA (rRNA). In the ribosome, the rRNA interacts with the messenger RNA to convert it to protein. In every living cell, rRNA performs in almost exactly the same manner. Just as all wheels are round and those that are not function poorly, there is but one good way to be rRNA, one good way to keep the machinery of life rolling. rRNA aids in the translation of mRNA to protein, and Woese hoped to translate the history of life as recorded in rRNA.
Ribosomal RNA is a keystone in life’s arch. Change it a little and the building begins to creak. Change it a lot, and it will fall. And so, unlike many genes, the genes of ribosomal RNA cannot change much, through time or species, over millions or even billions of years. As DNA is copied by cells’ tiny chemical monks, the DNA that codes for ribosomal RNA must be copied near perfectly, and so too the rRNA itself. Consequently, the differences in ribosomal RNA among organisms are small. Your ribosomal RNA is like mine. Mine is like a squirrel’s. A squirrel’s is very similar to a tree’s. The monks in cells make mistakes in copying the genes for ribosomal RNA, but they make few. Such mistakes accumulate very slowly through time.
Woese’s idea of understanding the evolution of a group of organisms based on some feature of their physical structure (such as their RNA structure) was not novel. Other biologists were doing similar work with proteins. The longer two proteins were separated in evolutionary time, the more different they would be. And this work all rested on research that had been done almost since Linnaeus began comparing external features of plants and animals. The greater the difference between the sex organs of two species, the longer those species have been changing. By looking at differences and similarities, it was becoming clear, one might assemble life’s evolutionary tree—or at least, most scientists imagined, parts of the tree.
When most biologists imagined an evolutionary tree, however, they thought about big species—tigers and tiger lilies. Woese imagined that microbes could be mapped onto a tree and put on their right branch. He wanted to “move the evolutionary discussion away from animals and plants and onto the molecular level, where it belonged in the twentieth century.”4 He thought this could be done with rRNA, in which he saw grand possibilities. Differences in rRNA, Woese posited, meant evolutionary differences in time. The more different two species were in their rRNA, the longer they had been separate. Leave two monks in two different dimly-lit rooms to copy a text. Let them make each subsequent copy based on the copy before it. With time, the mistakes they make will accumulate. The two sets of copies will diverge. If one knew the rate at which the monks made mistakes, he could look at the final products, the newest copies, and by comparing their differences estimate how long the two monks had been working apart from each other.
Woese wanted to know, when different types of organisms diverged, how long different lineages had been separated in their proverbial rooms copying the text. He also wanted to know what that first text looked like—to look into the recesses of time and find the first life. He began to compare the ribosomal RNA of different species in order to construct a microbial evolutionary tree. Woese began optimistically, believing that “only technological problems seemed to stand in [the] way: growing the various organisms and doing so in a low phosphate, radioactive medium; tweaking the…method to fit needs; finding needed help; and so on.” Those technological challenges would be formidable. His side project would be to initiate an entirely new field of inquiry using a method no one else had used (and that no one else would use for years). If he were right, his method would, like the microscope or the telescope, make visible what had long been unseen. But it was far more likely that he would be wrong.
At the outset, several things separated Woese’s work from everybody else’s. First, the rRNA analyses took far more time than the existing protein analyses and required unique skills that only he possessed. Second, no one, including his peers and his department head, knew why he would even try.5 Further, the questions he wanted to get at—the evolutionary tree of microbial life or even of life more generally—were viewed, as his colleagues were to make clear, as unanswerable. His fellow microbiologists wondered what he was trying to do. He needed to focus on work that would yield something. He seemed bothered, even obsessed. His willingness to participate in the niceties of daily society was dissolving. Biologists can, in focusing on a narrow piece of the world, focus so intensely that everything else seems irrelevant. The talk at the coffee pot is ridiculous banter, informal greetings a waste of time. Departmental meetings, advising students, emptying one’s garbage all become things left to someone else, someone not so involved. This is the kind of intensity that biologists, and scientists more generally, both fear and love. Scientists obsessed like this, if right, can be vindicated beyond dispute. Imagine, future generations might say, how much less he would have done had he brushed his hair more often. But scientists obsessed like this on a research question that does not lead to discovery are running very quickly into oblivion, drink, spirituality, madness, or all of the above.
Woese toiled. There is no other word for it. Ribosomal RNA, like all RNA, is made up of a simple alphabet of nucleotides: adenines, guanines, cytosines, and uracils.* Woese had to decode tiny sections of rRNA at a time. He had to do it through a method that ultimately converted the rRNA code into black smudges on photo paper. He would fragment segments of rRNA at each guanine nucleotide. Each of the resulting fragments was then fragmented again at each of the other types of nucleotides, systematically, monotonously. Woese could then photograph the distribution of the resulting fragments and—like a code breaker—work backward, letter by letter, to what their original arrangement of nucleotides must have been. As he split the rRNA into its bits, there was a sense of discovery every day in the lab. The photographs of the dissected bits of rRNA were beautiful, like abstract paintings, each one different and each one representative of some part of the evolutionary tree. Yet the tedium was overwhelming, something like trying to read a copy of Shakespeare left on the moon using a telescope. The beauty of the text, in this case the book of life, could be lost because of the difficulty of the process at hand.
Woese’s lab and office piled thick with photo sheets for RNA comparisons. His shelves were soon covered with yellow Kodak boxes to hold the film. Light boxes were brought in from who knows where and each one always had film on it. His chairs were taken over and then his desk and then the floor. This went on for weeks, months, and then years, without an answer, without a revolution, without a natural order. He went home some days saying to himself, “Woese, you have destroyed your mind again today.”6 He spent every day in front of the film sheets, brooding over patterns. After ten years of toil, he had cataloged just sixty bacterial species, sixty of the hundreds of thousands thought to exist.* He was forty-seven. He had written few papers based on his results. He had told few about what he was doing. He had taught no one his methods. He was the only one in the world who could decode rRNA and in doing so, he hoped, reveal life’s story. Like Leeuwenhoek with his microscope, he was alone.
It was then that one of Woese’s colleagues threw him a rope, albeit one that neither would consider important at that moment. His colleague Ralph Wolfe wondered if Woese would work with him on a separate project. Wolfe thought, contrary to public opinion, that Woese was making progress, but that the two of them together might make more progress on one particular group of organisms. Wolfe was the much better known of the two scientists and might have felt himself something of a mentor. Wolfe asked Woese if he would “run the rRNA” of a group of methane-producing bacteria he was working on, a group of life-forms found in sewer sludge and related environments. Woese had, several years earlier, talked with Wolfe about looking at some of these methanogens.7 Wolfe had not yet been able to grow them in the lab, a necessity for the quantity of material Woese needed.* But by the beginning of 1976, Wolfe could “grow a kilogram of methanogens” in bottles pressurized with CO2.8 These methanogens, Wolfe told Woese, were united by their unique enzymes and chemistry (they all produce methane as a by-product of their metabolism), and seemed very different from other bacteria.† No one knew quite what kind of bacteria they were related to. One possibility was that the methanogens were not really related to each other at all, but had simply evolved convergent traits to deal with their particular lifestyle. (For many of the initial samples, that lifestyle was living in sewage. One of the first species sequenced was Methanobacterium ruminatum, named for the cow guts it calls home.) The other possibility was that they were a unique evolutionary group. It was a perfect challenge for Woese.
By the time Wolfe offered Woese his specimens (first a species with the Linnaean name of Methanobacterium thermoautotrophicum, which, if you read Latin, says it all and then some), Woese had already constructed, species by species, a tree of life. It was his private tree based, at that time, on mere dozens of microbial species. He had shown it to few others, possibly no one at all. It was there, in his office, in yellow Kodak boxes, arranged in a way that was clear only to him. Woese would turn on his record player, put on an old jazz record, and marvel at what he had revealed. He was close to seeing the history of early life. He began—again letter by letter—to analyze Wolfe’s samples. He looked at the negatives in an upright light box, with the lights in the room off. He would look at the signs of the nucleotides, his own face lit by the light passing through the photos of rRNA nucleotides. He arranged the negatives, organized them, and then began to translate. Almost immediately, what he saw was surprising.
After the first step, the “signatures were remarkably distinct” from those of any bacteria he had yet seen. Each of the first nucleotide signatures he was accustomed to seeing in all bacteria was missing. When he did the more detailed work, to actually decode—nucleotide by nucleotide—the sequence of the RNA, the results continued to be surprising. Now he saw some RNA sequences that he associated with bacteria, but others were missing. It was as if the RNA were from something that was half bacteria, half eukaryote. As Woese would later say in an interview, “by this point one stops wondering what they have done wrong and begins to ask what this all means.” He had an idea, but before he said anything he repeated the whole process from scratch, a second, and then a third, and then even more times.9 The results were the same.
The samples were not, Woese thought, bacteria, nor were they eukaryotes,* but instead something else entirely—some new form of life. Now here was the kind of discovery Woese had worked for all those years. Woese had never been prone to outbursts, but if he ever did yell with joy and dance in his office of rRNA and jazz, these were the days. Woese rushed to find his postdoctoral fellow, George Fox, to “share [his] out-of-biology experience” with someone. Fox was skeptical, so Woese ran to tell Wolfe, saying, as Wolfe remembers, “these methanogens are not bacteria.” Wolfe told Woese they had to be. “Of course they are bacteria; they look like bacteria…Now, calm down; come out of orbit.”10
The next step was to examine other methanogens and other species that were morphologically similar to the methanogens. By the end of the year, the team, led by Woese, had decoded the gene sequences of the RNA of five other methanogens. More were in the works, but the result was getting more and more clear: the methanogens were very different. Once “a second methanogen was characterized and showed itself to be related to the first, there was no doubt” that they had found a new form of life, Woese would later say. This form of life had been different from the others, bacteria and eukaryotes, for a very long time. Understanding how these methanogens related to other kinds of life was, it seemed to Woese, a big discovery. Woese later wrote of the moment, “Darwin had long ago said that there would come a day when there would be ‘very fairly true genealogical trees of each great kingdom of nature.’ Perhaps that day was at hand!”
Woese immediately wrote two papers about his new finds. One paper was written with Wolfe and his lab, and focused on the new kind of microbe.* The other paper, however, written with George Fox, Wolfe’s postdoc, was the one that would prove more controversial.11 The first place where anyone saw the results of the second paper was in the newspapers. Woese was forty-nine. He had worked without recognition for decades, but that was to change this day. The news media saw an advance copy of the edition of the Proceedings of the National Academy of Sciences in which the Woese and Fox article was to appear. The media found the result tantalizing. The New York Times ran the headline, “Scientists Discover a Form of Life That Predates Higher Organisms,” on the front page of the November 2, 1977 edition. The first lines of the article summed up the outrageousness of what the paper was about to claim—that scientists had described a “third kingdom of living material composed of ancestral cells that abhor oxygen, digest carbon dioxide, and produce methane.” Woese was thrilled with the popular attention for the find, but his mood would change.
Woese had discovered, or he so argued, an entirely new domain of life. The monks in these single cells, however faithful to the ancient text they tried to be, had long been separate from those of all other cells. The authors went on to argue that there are three major divisions of life: one is bacteria, one is the lump of flesh and plant that includes all eukaryotes. The third is archaea,* the group that Woese, Wolfe, and their labs had just discovered—essentially in specimen jars in their offices. Suddenly, Margulis, among others, had an entirely new lineage of organisms whose origin she had to explain.
In Woese’s scheme, not only are humans a tiny branch on the tree of life, but so are mammals, insects, and in fact all other animals. From an evolutionary perspective, most of life is microbial—everything else a minor branch, a fit of evolutionary whimsy. This is what Woese has gone on to contend for the rest of his life. To the extent that he changed his opinion, it was only to become even bolder in his statements, to argue, through new results, that he could see even farther back in time.
Woese does not think personality is part of science, that scientists themselves are an important part of how science should be recorded. As a consequence, we have few direct views into what he was thinking during those years in which he was buried in his office working. Those views we do have, though, speak volumes.
The day the announcement of Woese and Wolfe’s finding came out in the newspaper, Woese was thrilled. He thought the revolution had begun. He asked a woman at a fast-food restaurant if she knew who he was. She looked at him, thought for a while, and struggled for the answer. He prompted her by mentioning his discovery. She then realized, oh yeah, “You’re Bob’s dad.”12 He was, of course, but Woese had thought deeply, without whimsy or humor, that his discovery would be big enough that the woman working the checkout line in a fast-food restaurant would know who he was. He was wrong.
It was, in many other ways, not Woese’s day. What followed was anger, hate mail, and promises of academic oblivion. Both Woese and the relative innocent in this enterprise, Wolfe, would be attacked. Wolfe recalled that: “One Nobel Prize winner, Salvador Luria, called me and said, ‘Ralph, you’re going to ruin your career. You’ve got to disassociate yourself from this nonsense!’13 Wolfe “wanted to crawl under something and hide.”14 He did not disassociate himself (though he did take a vacation), but nearly everyone else did.
The criticism of Woese was never very public. But it was the “talk of corridors.” Woese was “itching for [his critics] to come after [him] in print. But none of them would!” So Woese kept working, knowing that many of his colleagues quietly doubted him. Woese thought the “matter would resolve scientifically.”
There were reasons to be skeptical of the findings. The question Woese proposed to address—the relatedness of the deepest lineages of life—was seen as unanswerable, too deep in the early history of life on Earth. If Leeuwenhoek looked up God’s dress, Woese was trying something bolder, even more inappropriate. He was trying to do so with a new ribosomal RNA method that no one else was using. No one else was familiar with it. No one else had confidence in it. In short, Woese had proposed to answer an unanswerable question with an unlikely and unknown method. Even for those who knew his method, it seemed, well, insufficient. Woese had proposed a new domain of life and a reordering of life’s tree to put man, all animals and plants, as minor players circling a microbial Earth. He had, late at night, with charcoal on the cave walls of science, sketched a tree. At its base was a microbe, perhaps something like an archaea. From that microbe would descend three great lineages, the archaea, the bacteria, and the eukaryotes. Within the eukaryote branch, the most recent of the tree, were all the fungi, all the plants, all the protists, and all the animals. All vertebrates were a twig on the small, recent branch of the animals—too small to even be worth drawing. Too small a bud to make it into the big story, which was, in nearly its entirety, about microbes.
He went back to science, back to work on archaea, for thirty years. He had made an extraordinary claim and despite everything, he still believed in his work. He went back to his light table and went through sequences one by one. He added other microbial lineages to his analyses. He studied, along with a growing number of other scientists, other unique features of the archaea. They had different lipids (fats). They had different metabolisms. If people thought him a bit of a crank before, this would not help things. He buried himself in his discovery. Since Leeuwenhoek, there were the microscopic things and the big things. The big things were the more important—the main story. The microbes were the backstory. Woese was trying to turn the backstory into the plot.
Woese was like Leeuwenhoek. He could see something others had not seen. He could see it because of his method. Like Leeuwenhoek, he was confident. What remained to be seen was if, like Leeuwenhoek, he was right.
Vindication for big, speculative ideas comes slowly. It must trickle in on the backs of new results. It comes paper after paper, until at some undefined point, what was once heretical has become the status quo. Copernicus published, posthumously or nearly so, his treatise suggesting that the Earth and other planets circle the sun. It would take generations for this idea to become fully accepted. A few believed right away, but one of those, Galileo, went on trial for that belief and another, Bruno, was burned at the stake. But it was not long before average citizens looked up and imagined the sun as stationary, and the Earth as moving. If you now open an introductory college biology book, you will, more likely than not, find that Carl Woese is mentioned alongside the idea that there are three main divisions of life. We now accept as given these new divisions of life. They are presented in introductory biology classes by tired professors who flash the information up on the board early in the morning, read through it, as they gaze into groups of half-dozing students, less worried about their place relative to the archaea than about what they will do that evening, who the girl with the long hair is in front of them, or why their professor has now worn the same shirt three lectures in a row. But don’t be confused. Woese’s result was both correct and revolutionary. It’s just that we quickly grow used to some revolutions once they happen; the idea that the Earth circles the sun is now, on most days, unremarkable.
It would have been easy for Woese to give up. He was unsupported. He was persecuted. If he had given up, we might still believe archaea to be nothing more than strange bacteria. Fortunately, Woese did not give up or become more moderate. He was propelled by continued finds, new nuances on his big story. This is one of the lessons of history: if you are right with an outrageous theory, you must persist, despite everything, for it to be accepted. You must persist even when your brightest friends doubt you. (Of course, this only works if you are right.) Woese knew he was right, and eventually others would come to agree. But had he been wrong he might have also persisted. Had he been wrong he would still be wrong, persisting, insisting, marginalizing himself further and further.
Woese remains, by most accounts, bitter about the past. Now, as he formulates new theories, he does so perhaps more ferociously than he might have. Once he began to know the relationships among the living groups of organisms, he could say, with confidence, that the whole evolutionary story of plants and animals was relatively unimportant, marginal, late, and insignificant. This left him with a far harder task than understanding how rhinos relate to rats, or even archaea to bacteria. He wanted to know the details of the evolution of those first single cells, billions of years ago. It is in searching for that mother of cells that Woese’s story meets that of Lynn Margulis. Their stories meet in the way in which most scientists meet—a little awkwardly, indirectly, and with more than a little passive aggression.
The first response to firm scientific conclusions should be doubt. But that said, for the moment, Woese’s division of life into three domains enjoys broad support. It seems a relatively firm conclusion. The archaea are, to put it simply, just different.
Seeing how archaea are different requires a little imagination. Picture a single archaeal cell, the size of a house. Like bacteria, archaea come in rods, spiral shapes, lobed shapes, and even rectangles. Like bacteria, archaea have cell walls. Bacteria and archaea have the same structures inside their cells, mitochondria, cytoplasm, ribosomes, and the like. The houses, overall, seem similar—similar walls, the same rooms, a big open central area. Then come the differences. The biggest differences are simply in the materials used to build the house, the bricks, mud, and twigs. The fats in the cells of archaea and bacteria differ, as do the sugars and proteins. Some of the composition of archaea more closely resembles that of eukaryotes than it does that of bacteria, but most of the differences are simply unique. The houses are built to similar specifications, but of different materials. In most cases, the composition of archaeal cells differs in ways that make them tougher, more resistant to heat, cold, and other extremes. Nearly every extreme environment that has life has archaea, and in abundance. In more favorable environments, archaea are rare. It is as if the differences between archaea and other cells make archaea tougher but slower, less able to compete when toughness is not required (the tortoise to bacteria’s hare). These differences between archaea and bacteria might not seem great, but they are far greater than, for example, the differences between human cells and the cell of a single paramecium. A paramecium is just like each of our billions of cells. All of our gaudy bells and whistles, arms and organs, self-awareness and locomotion, are just a consequence of the arrangement of those cells in new ways.
Woese is best known for his discovery of the archaea, for noticing the differences between them and everything else, but in rebuilding the tree of life he also accomplished much more. He provided some of the strongest support for Lynn Margulis’s theory of serial endosymbiosis—the formation, sequentially, of new lineages of life through symbiosis. Woese reconstructed the tree of life and in doing so studied the rRNA in archaea, bacteria, and eukaryotes. However, because rRNA is so basic and necessary that it is found not only in our cells and in our mitochondria, but in every living thing on Earth, it continues to offer the deepest insight into the earliest life. If Margulis were right that our mitochondria had once been free-living microbes, their rRNA should be more similar to that of other microbes than it is to the rRNA in our nucleus. And it was. Here was almost unassailable support for Margulis. The mitochondria and even chloroplasts could be mapped onto Woese’s tree of life, as easily as if they were still free-living microbes living in the ground.
Left uncertain, though, was the origin of the centrioles, cilia, and flagella. Margulis hangs tight to her original ideas, waiting for evidence, and continuing to look. Nearly everyone seems to doubt her theory for the origin of the centrioles, cilia, and flagella. Yet she presses on. It is hard to believe that a biologist, even Margulis, could get everything right in a paper she wrote while just barely having finished her PhD. Some of the details must have been wrong, but so much has already been proven that the centriole theory is the only remaining candidate. On the other hand, no one believed her before either, and history seems to nearly always prove her right. Regardless of the fate of the centrioles theory, one thing is certain: the idea that our cells were composed of two separate and ancient lineages was heretical. It was a major new discovery. It fundamentally changed how we consider the workings of our cells. Lynn Margulis divided us, Carl Woese divided all life, and none of it can ever be put back.