The Tangled Tree

by David Quammen

  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.