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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?”

The Tangled Tree: A Radical New History of Life

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