The Tangled Tree

by David Quammen

  But the tree hypothesis works poorly for the history of bacteria and archaea, with all their sideways exchanges; and it works imperfectly for everything else. Darwin can’t be blamed. He didn’t have molecular phylogenetics to snarl his thinking. He didn’t know about horizontal gene transfer. He did the best he could, which was exceedingly well, with the evidence he could see.

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  Axel Erlandson was a Swedish-born American farmer, brought to the United States as a child, raised in Minnesota, drawn to the Central Valley of California along with his family, in 1902, by the promise of irrigated land and extended sunshine. He married, had a daughter, and set to growing beans and other crops on his own place, near Hilmar, California, which is halfway between Modesto and Merced. One day he noticed a natural inosculation in his hedgerow: two branches from two different shrubs, kissing and fused. Inspired by this anomaly, as John Krubsack in Wisconsin had been inspired, Erlandson launched himself upon the same odd hobby: shaping trees into amusing, unnatural shapes. He learned by trial and error and achieved amazing results. His methods included pruning, grafting, bending, supporting his entangled saplings with external stakes and scaffolds until they were firmly grown into position, and, as he said teasingly when asked about his knack with bizarre trees, “I talk to them.”

  Erlandson favored limber species such as sycamore, willow, poplar, birch, and (like Krubsack) box elder. His creations became known by descriptive names. He grew a Needle and Thread Tree, featuring a crosshatch of diagonal limbs, some passing through holes in others. He grew a Cathedral Window, resembling a great composite of stained-glass panes, rising from ten small trees planted in a row. He grew a Ladder Tree and a Telephone Booth Tree and a Tepee Tree and a Double Spectacle Tree and an Archway Tree and a Revolving Door Tree and a Nine-Toed Giant. He grew six sycamores into a single Basket Tree. No one had ever seen such shapes—not among natural trees, wild or domestic, growing by their own arboreal rules. Erlandson, in his mind’s eye, saw trees that couldn’t exist, and he made them happen. The man was benignly demented.

  Or maybe not. After twenty years of this, with World War II just over and tourism in California beginning its postwar boom, he got the idea to convert his arboreal sculptures into a roadside attraction. Maybe his hobby could yield a bit of cash.

  He bought land on the old stage road between San Jose and Santa Cruz, a road that led from burgeoning suburbs toward the ocean, and he moved his strange nursery to the new property. He transplanted those novelty trees that were transplantable, cut the others and brought them like furniture, and began growing still others. In 1947 he opened for business. There wasn’t much, but some. Visitors pulled over, stopped in, rang a bell, and Erlandson admitted them, for a small fee, to his collection—a steady trickle of customers, at least until a newer route, Highway 17, diverted most traffic from the old road. In a good year, he made more than $320. He called his place the Tree Circus.

  The further history of Axel Erlandson is not what concerns us. I’m simply underlining a point about the mystifying unnaturalness of topiary. The other circus of peculiarly shaped trees, as you’ve read, grew from genomic data and phylogenetic analysis during the late 1990s and into the first two decades of this century. That topiary enterprise continues. Ford Doolittle has made his “retreat” into philosophy, to think about what it all means, but many of his former grad students and postdocs are now prominent researchers in this field, helping illuminate the deep history of life. Bill Martin and his colleagues continue doing important work, likewise Peter Gogarten and Jeffrey Lawrence and Eugene Koonin and many others, too many to count let alone list. Younger researchers, fresh voices—such as Thijs Ettema, a Dutchman in Sweden, studying novel lineages of archaea and the light they may cast on early evolution—have emerged to prominence in the past decade. The huge increase in sequenced genomes, available to all researchers through public databases, and of computing power and software tools to analyze those genomes, has pushed the waves of discovery and insight into high, breaking crests. No one can keep track of it thoroughly or reduce it to a linear narrative. But amid all the new data and phenomena and ideas, these scientists are addressing some very large questions.

  Three in particular stand out. First question: Is it true that Charles Darwin was wrong? If so, about what? Has his theory of evolution been grievously challenged, or just amended? Second question: What are the origins of the eukaryotic cell? Endosymbiosis, and the ideas of Merezhkowsky and Margulis and its other proponents, only begin to answer this one. Mitochondria and chloroplasts as captured bacteria, okay. But what about the rest of the epochal transition, from prokaryote to eukaryote, that occurred about two billion years ago? How did the cell nucleus come to be? What was the identity of the host cell, the receptacle, within which all these fancy improvements occurred? What exactly were the materials, and what were the circumstances, that converged to become such a complex cellular entity, ancestral to all animals, all plants, all fungi, and other eukaryotic creatures? How did that complexity begin?

  Third question, and the closest to home: What implications do these discoveries carry for the concept of human identity? What is a human individual? What are you? The reality here is more strange than you might think.

  PART  VII

  E Pluribus Human

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  The realization that bacteria and other microbes inhabit the healthy human body goes back a long way, at least to the day when Antoni van Leeuwenhoek scraped some plaque off his teeth and looked at the stuff through one of his lenses. From there it was a great leap, about three hundred years, to the point where scientists could appreciate the extent of our colonization by other creatures and begin to census them. Modern microbiology arose in the meantime. But the shock that Leeuwenhoek experienced, finding alien creatures in his own mouth, would be matched later by the shock of finding alien genes in our own genomes, let alone whole menageries of intact microbes thriving amid the various compartments and surfaces of our bodies.

  No doubt you’ve heard the term microbiome. It’s a great scientific buzzword nowadays, in the news, in the magazines, in the grant proposals of many scientists. It’s also an apt label for the phenomenon of tiny creatures as important constituents within big creatures, of which recent years have brought an exploding recognition. The word is old but Joshua Lederberg helped popularize it to mean “the ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space and have been all but ignored as determinants of health and disease.” As that suggests, microbiome commonly serves to mean “human microbiome,” the community of microbes resident within us. Every other sort of complex multicellular creature has its own version of such indwellers. The horse microbiome and the tiger microbiome each constitutes a different community living in its own little world. Ours is ours. These particular bugs have evolved as participants in peoplehood. And we have evolved with a deep dependence on them.

  Of course, the human microbiome is not one invariant list of microbial species, common to all people at all times. It’s a set of possibilities. It’s kaleidoscopic. Just as “the human genome” is a single phrase suggesting a single entity but really encompassing much variation from one person to another, so is “the human microbiome.” When I say “these particular bugs” are participants in peoplehood, I mean a whole roster of residents and combinations of residents within and upon the human body, differing somewhat from person to person and changing with circumstances and time.

  That changeability of the microbiome is why it’s relevant to a new understanding of human health. The composition of resident microbes, for each of us, is contingent—contingent on who we are, what we do, how we’ve been born and raised, where we go, what we eat. And its contingencies have impact.

  The human microbiome has become a major focus of research, and of medical concern, for its involvement or suspected involvement in a broad array of unhealthy conditions: obesity, childhood diabetes, asthma, celiac disease, ulcerative
colitis, certain kinds of cancer, Crohn’s disease, and others. A healthy person, scientists have realized, carries a healthy and diverse microbiome; and if the microbiome is depleted or disturbed or left undeveloped, by one factor or another, there can be hurtful effects. Just as the presence of certain microbes in a human body can be problematic (we call that infectious disease), the absence of certain microbes can be problematic too. Take away Bacteroides thetaiotaomicron from his or her gut, and a person might have trouble digesting vegetables. An imbalance among microbes, too many of one kind, too few of another, can also cause trouble. Disrupt the bacterial community of a healthy person’s colon by administering an antibiotic, and the small resident population of Clostridium difficile—surviving the drug, but now freed of competition, because so many other bacteria have been eliminated—may explode to a raging infection. It may weaken the bowel wall, cause fever and diarrhea, possibly even death.

  A recent estimate suggests that each human body contains about thirty-seven trillion human cells. It also contains about a hundred trillion bacterial cells, for almost a three-to-one ratio of bacterial to human. (Another study proposes a lower ratio, roughly one-to-one, but that still means thirty-seven trillion bacterial cells in your body.) And this doesn’t even count all the nonbacterial microbes—the virus particles, fungal cells, archaea, and other teeny passengers—that routinely reside in our guts, our mouths, our nostrils, our follicles, on our skin, and elsewhere around our bodies. These stowaways may represent more than ten thousand species (or “species,” given the fuzziness of the category as applied to prokaryotes). About a tenth of that diversity, maybe a thousand species, are bacteria living just within the human gut. Because each of our trillions of microbiomic cells is generally much smaller than a human cell, the complete microbiome constitutes only about 1 percent to 3 percent of our body’s mass. In a two-hundred-pound adult, that’s roughly two to six pounds. In volume, maybe three to nine pints. Still, they’re busy and they’re consequential, those few pints of cells.

  But that’s not the half of what I’m getting at here. Other books, some of them technical, some of them popular, have recently described the nature and workings of the human microbiome. Among the best of the latter is Ed Yong’s I Contain Multitudes, an encyclopedic and lively survey of microbial ecosystem dynamics in humans and other species. My purpose is different, and there’s no need to cover much of the same ground. But since the microbiome has entered our cultural vernacular, it makes a good starting point toward something else, something even more fundamental and tricky: a new appreciation of the composite nature of human identity.

  Leeuwenhoek reported his mouth-creatures epiphany in a letter to the Royal Society, dated September 17, 1683, along with further observations on similar samples from four other people. To his naked eye, this dental plaque appeared as “a little white matter, which is as thick as if ’twere batter.” Magnified under his microscope, though, it was more: “I then most always saw, with great wonder, that in the said matter there were many very little living animalcules, very prettily a-moving.” The biggest of them “had a very strong and swift motion, and shot through the water (or spittle) like a pike does through the water.” That’s fast: a pike is arrow-like compared with a bass or a carp. The smaller beasties “spun round like a top.” It was a rich, busy ecosystem, especially as collected from one of Leeuwenhoek’s subjects: an old man who had gone a lifetime without ever brushing his teeth. In the old man’s savory offering of oral goop, he found “an unbelievably great company of living animalcules, a-swimming more nimbly than any I had ever seen up to this time.” These bugs included largish ones that “bent their body into curves in going forwards.” He was looking at microbes of various sorts, their identities now indeterminable from the sketchy evidence he left. But all the spinning and curving behavior suggests that spirochetes—corkscrew bacteria—may have been among them.

  That possibility is supported, and set in broader context, by a report from a team of medical microbiologists more than three centuries later, in 1994. Their leader was Ulf B. Göbel of the University of Freiburg, in Germany. Searching for biodiversity in the mouth of a twenty-nine-year-old woman suffering severe periodontitis (gum disease, which was rotting her teeth away from the jawbone), these scientists found dozens of kinds of spirochetes that were assignable to a single genus. The genus was Treponema, notorious for Treponema pallidum, the little demon that causes syphilis. Other treponemes, it turns out, are less dramatic though still troublesome. They cause periodontitis of the sort seen in that woman. But what makes this case notable for us is not the diversity of bone-eating corkscrews that were rampant in one person’s mouth. What makes it notable is that Göbel’s group did its work using the methodology of Carl Woese.

  More specifically, they identified those many different kinds of oral spirochete by sequencing and comparing samples of 16S rRNA. But they went beyond Woese, who had done his work by growing bacteria and other microbes in cultures and then extracting their ribosomal RNA. Sometimes the bugs can’t be grown in captivity. They’re too feral and sensitive for culturing in a lab. Under those circumstances, it takes a different method to detect new, unknown microbes. That method, as Göbel and his colleagues acknowledged, had been developed by Woese’s great friend and foremost acolyte, Norman R. Pace.

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  Norman Pace grew up during the 1950s in a small Indiana town, a bright kid with an early taste for science, who blew out his left eardrum during a home-chemistry-lab experiment and, like Ford Doolittle, got serious and saw his career path in the aftermath of Sputnik. He attended a summer science camp during high school, then went off to college in the big city: Bloomington. In 1964 his prairie horizons widening, he moved to the University of Illinois as a grad student, attracted by the prospect of doing a PhD under Sol Spiegelman, an eminent figure by then, renowned for his work on nucleic acids. Carl Woese arrived in Urbana about the same time, thirty-six years old, recruited as an associate professor but largely unknown, and just beginning work toward his early book on the genetic code. Woese’s lab was along the same corridor as Spiegelman’s, on the third floor of Morrill Hall. Pace, again like Ford Doolittle but several years earlier, seems to have found the young Woese more companionable, and in some ways more inspiring, than the crepe-soled and spooky Dr. Spiegelman.

  “We would talk and be friendly. He was just down the hall,” Pace told me fifty years later, as we sat in his lab at the University of Colorado, in Boulder. “And he was doing some stuff I was pretty interested in.” But maybe doing was the wrong word for such deep speculations, and Pace corrected that to “—thinking about stuff that I was pretty interested in.” Those interests went down through the mechanism of the genetic code, Francis Crick’s favorite puzzle, to the evolutionary origins of the code, and beyond that to the earliest amorphous twitches of life itself. Woese was pondering big questions, pushing the boundaries of what seemed accessible to scientific investigation, not whimsically but with a fierce desire to know. “Smart, congenial guy on the corridor,” Pace said, “thinking about origins of life, and those sorts of things that legitimate scientists didn’t think about.” He laughed. “We interacted a lot during the course of those years.” Pace the grad student asked Woese the young professor to be on his dissertation committee. Woese agreed, and their friendship grew.

  By now, it was the late 1960s. Pace was a fit and adventurous young man with a passion for caving, a fondness for motorcycles, and a lively wife, Bernadette Pace, who had her own doctorate in molecular biology. He favored the BMW R69S as a highway bike and rode one, with Bernadette holding on behind him, from Germany to Turkey back in the day. Then she wanted one for herself. “That was before she took up trapeze,” Pace told me. Bernadette became a high-flying trapeze performer of professional skill, good enough to perform with the Carson & Barnes Circus when they had an injury (which happens often in trapeze). Norm and Bernadette erected a high-flying setup for her in their yard, and sometimes when the couple threw parties
, and she performed for their friends, he would put on a top hat, tights, and a bow tie, and serve as ringmaster. None of that vitiated the seriousness of the science they did, with Bernadette his coauthor on more than a dozen arcane papers. Nor did it diminish him in the eyes of Woese, a conservative man though a radical thinker, who merely viewed Norman’s more robust activities as “swashbuckling.”

  After getting his doctorate, then two years on a postdoc fellowship, then leaving Urbana for his first academic job, Pace stayed closely in touch with Woese. He established his own lab at the National Jewish Hospital and Research Center, in Denver, and continued research on what had been his dissertation topic, the replication of RNA. Ford Doolittle came out to Denver from Urbana and did a postdoc under his roof. Then so did Mitch Sogin, Woese’s brilliant handyman for the early sequencing work, still interested in ribosomal RNA. Pace coauthored papers with both of them, and with Woese too, during the 1970s.