What an wonderful article! It takes an abstract topic, makes it immediately apparent why we readers should care, and then takes the time and space required to explain the technical details. Grace, humor, precision - this article makes me glad to subscribe to the Times.
•••••••••••••••••••••••••••••
Wikipedia - Carl Woese
Simple English Wikipedia - Carl Woese
•••••••••••••••••••••••••••••
New York Times - The Scientist Who Scrambled Darwin’s Tree of Life
How the microbiologist Carl Woese fundamentally changed the way we think about evolution and the origins of life.
By David Quammen
August 13, 2018
On Nov. 3, 1977, a new scientific revolution was heralded to the world — but it came cryptically, in slightly confused form. The front page of that day’s New York Times carried a headline: “Scientists Discover a Form of Life That Predates Higher Organisms.” A photograph showed a man named Carl R. Woese, a microbiologist at the University of Illinois in Urbana, with his feet up on his office desk. He was 50ish, with unruly hair, wearing a sport shirt and Adidas sneakers. Behind him was a blackboard, on which was scrawled a simple treelike figure in chalk. The article, by a veteran Times reporter 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.
This “separate form of life” would become known as the archaea, reflecting the impression that these organisms were primitive, primordial, especially old. They were single-celled creatures, simple in structure, with no cell nucleus. Through a microscope, they looked like bacteria, and they had been mistaken for bacteria by all earlier microbiologists. They lived in extreme environments, at least some of them — hot springs, salty lakes, sewage — and some had unusual metabolic habits, such as metabolizing without oxygen and, as the Times account said, producing methane.
But these archaea, these whatevers, were drastically unlike bacteria if you looked at their DNA, which is what (indirectly) Woese had done. They lacked certain bits that characterized all bacteria, and they contained other bits that shouldn’t have been present. They constituted a “third kingdom” of living creatures because they fit within neither of the existing two, the bacterial kingdom (bacteria) and the kingdom of everything else (eukarya), including animals and plants, amoebas and fungi, you and me.
Charles Darwin himself suggested (first in an early notebook, later in “On the Origin of Species”) that the history of life could be drawn as a tree — all creatures originating in a single trunk, then diverging into different lineages like major limbs, branches and twigs, with leaves of the canopy representing the multiplicity of living species. But if that simile was valid, then the prevailing tree of 1977, the orthodox image of life’s history, was wrong. It showed two major limbs arising from the trunk. According to what Woese had just announced to the world, it ought to show three.
Woese was a rebel researcher, obscure but ingenious, crotchety, driven. He had his Warholian 15 minutes of fame on the front page of The Times, and then disappeared back into his lab in Urbana, scarcely touched by popular limelight throughout the remaining 35 years of his career. But he is the most important biologist of the 20th century that you’ve never heard of. He asked profound questions that few other scientists had asked. He created a method — clumsy and dangerous, but effective — for answering those questions. And in the process, he effectively founded a new branch of science.
It began with a casual suggestion made to Woese by Francis Crick, the co-discoverer of DNA’s structure, who mentioned passingly in a scientific paper that certain long molecules in living creatures, because they are built of multiple small units, coded in sequences that change gradually over time, could serve as signatures of the relatedness between one form of life and another. The more similar the sequence, the closer the relative. In other words, comparing such molecules could reveal phylogeny. The new branch of science is called 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 ancient history of life from the different sequences built into such molecules. The molecules mainly in question were DNA, RNA and a few select proteins. Carried far beyond Woese and his lab, these efforts have brought unexpected and unimaginable discoveries, fundamentally reshaping what we think we know about life’s history, the process of evolution and the functional parts of living beings, including ourselves.
Woese vanished into his lab, but his insights and methods, and his successors in applying them, have produced in particular one cardinal revelation: The tree of life is not a tree. That old metaphor is obsolete. Life’s history has been far more tangled.
The idea of a “tree of life,” variously construed, goes back a long way in Western thinking — to the Book of Revelation, for instance, wherein the image of the tree seems to represent Christ, with his leafy and fruity blessings for the world. In 1801 the French botanist Augustin Augier used a tree as a kind of chart, for bringing order to the diversity of plants. He clustered major groups together on limbs and depicted minor groups as leaves at the ends of smaller branches. This wasn’t evolutionary thinking; it was just data management.
That simple, pragmatic use of the arboreal metaphor changed profoundly in 1837, when young Charles Darwin, just back from the Beagle voyage and scribbling reckless thoughts in a notebook, drew a small sketch of the first evolutionary tree. Above it he wrote: “I think.” This tree was hypothetical, its branches labeled with letters, not actual species, but what it meant to Darwin was: I think all creatures have arisen from a single source, diverging and changing somehow over time. He didn’t yet have a theory of the evolutionary process — the concept of natural selection would come later — but his sketch at least gave him an image of evolutionary history and its results. From that he could work backward, attempting to deduce the mechanism.
He took his time and refined his ideas, working secretly. Twenty-two years later, finally announcing his theory in “On the Origin of Species,” Darwin 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.” But there was a big difference between his tree and Augier’s, or anyone else’s: His implied common origins (in the trunk), descent with modification (in the limbs) and adaptation by evolutionary change (in the twigs and leaves).
That image, the tree, defined the shape of evolutionary thinking from Darwin’s time until the 1990s, when new discoveries following from Woese’s rebel initiative suggested that it was inadequate. Among the most basic elements of the tree figure is continuous divergence, only divergence, through the passage of time and the lineages of creatures. Limbs never converge, never fuse. Those arboreal realities fit the canonical belief that genes flow only vertically, from parents to offspring, and can’t be traded sideways across species boundaries. What made Woese the foremost challenger and modifier of Darwinian orthodoxy — as Einstein was to Newtonian orthodoxy — is that his work led to recognition that the tree’s cardinal premise is wrong. Branches do sometimes fuse. Limbs do sometimes converge. The scientific term for this phenomenon is horizontal gene transfer (H.G.T.). DNA itself can indeed move sideways, between limbs, across barriers, from one kind of creature into another.
Those were just two of three big surprises that flowed from the work and the influence of Woese — the existence of the archaea (that third kingdom of life) and the prevalence of H.G.T. (sideways heredity). The third big surprise 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 41 years ago, were not known to exist. How so? Because 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 — may have descended from these odd, ancient microbes. Our limb, eukarya, seems to branch off the limb labeled archaea. The cells that compose our human bodies are now known to resemble, in telling ways, the cells of one group of archaea known as the Lokiarcheota, recently discovered in marine ooze, almost 11,000-feet deep between Norway and Greenland near an ocean-bottom hydrothermal vent. It’s a little like learning, with a jolt, that your great-great-great-grandfather came not from Lithuania but from Mars.
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 complicated, than we realized. The tree of life is more tangled. Genes don’t just move 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 (to use a different metaphor preferred by some scientists) an infection that transforms identity. They called it “infective heredity.”
Such revelations, beginning in 1977 and continuing to break in the world’s leading scientific journals — but seldom explained to the general public — challenge us to adjust our basic understanding of who we humans are. You can blame it, if you want to blame someone, on the little white-haired man in Urbana, Ill.
Carl Woese was tangled himself. A proudly independent soul, very private, he 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 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 — 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.
By 1969, at age 41, Woese was a tenured but unexceptional professor at the University of Illinois in Urbana. On June 24 that year, he wrote a revealing letter to Francis Crick in Cambridge, England. He had struck up an acquaintance with Crick about eight years earlier, while Woese was working at the General Electric Research Laboratory in Schenectady, N.Y., as an unguided biophysicist not quite sure what his employers wanted from him. Crick was already world renowned for the co-discovery, with James Watson, of DNA’s structure, but he hadn’t yet won his share of the Nobel Prize. The Woese-Crick interaction began as a tenuous exchange of courtesies through the mail — Woese requesting, and receiving, a reprint of one of Crick’s papers on genetic 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, and all forms of cellular life (that is, not including viruses) were classified as one or the other. Although bacteria are still around, 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 farther back? Woese was always an ambitious thinker. “There is a possibility, though not a certainty,” he told Crick, “that this can be done by using the cell’s ‘internal fossil record.’ ” What he meant by “internal fossil record” was 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, in one lineage and another, had diverged. And from such deductions, such ancestral forms, Woese hoped to glean some understanding of how creatures evolved in the very deep past. He was talking about molecular phylogenetics, without yet 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” of living cells?
Woese had in mind a tiny molecular mechanism, common to all forms of cellular life, 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 protein transports oxygen through the blood of vertebrate animals. Architectural instructions for building hemoglobin molecules are encoded in the DNA of the animal, but where is hemoglobin actually produced? In the ribosomes. They are the core elements of what Woese called the translation apparatus. In plain words: Ribosomes turn genes into living bodies.
These particles had only recently been discovered, 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 another of Crick’s brilliant colleagues, 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 analogy was a strand of RNA — that particular sort called messenger RNA, because it carries messages from the cell’s DNA genome to the ribosomes, telling them which amino acids to assemble into a specified protein. 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 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 10 million ribosomes; a single cell of the bacterium Escherichia coli, or E. coli, might get by with just tens of thousands. Each ribosome might crank out protein at the rate of about 20 amino acids (the constituent units of all proteins) per second, 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.
“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.) 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, 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.
In the handful of years following his letter to Crick, Woese developed a unique methodology for this task, limning life’s history by way of the “internal fossil record” within living cells. The mechanics 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. Courageous young grad students, postdocs and technical assistants, under a driven leader, were pushing their science toward points where no one had gone before. OSHA, though recently founded, was none the wiser.
Woese had already settled on that one universal element of cellular anatomy, the ribosome, as the locus of his internal fossil record. But there remained a crucial decision: Which ribosomal molecule should he study? He settled on a longish molecule that serves as a structural component in one of the two ribosomal subunits. Its shorthand label is 16S rRNA. In English we say “16 S ribosomal RNA.”
Mitchell Sogin worked in Woese’s lab, as a grad student and chief technical assistant, during these crucial years leading to the archaea discovery. He had come to the University of Illinois planning to do pre-med, shifted his focus, stayed for a master’s degree in “industrial microbiology” (essentially food-preservation and fermentation technology), and then drifted into Woese’s ambit because of shared interests in deeper questions. Woese noticed something about 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 at creating the tools for such work.
Another professor had ordered and paid for a collection of apparatus to be used for RNA sequencing, then accepted a position at Columbia University, leaving behind the hardware. “So Carl inherited that equipment, but he had no one that knew how to use it,” Sogin told me, in his office at the Marine Biological Laboratory in Woods Hole, Mass., almost 50 years later. No one who knew how to use the equipment, that is, until Sogin joined his lab. Sogin learned as much as possible about how to operate these tools, then became Woese’s handyman as well as his doctoral student, assembling and maintaining an array of paraphernalia 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 film images of RNA fragments, the shorter pieces of the molecule once Sogin had used enzymes to cut them into workable bits. Sogin himself built these fluorescent light boxes, on which the images of the fragments, cast by radioactive phosphorus onto large X-ray films, could be examined. He converted an entire wall of bookshelves, using translucent plastic sheeting and fluorescent tubes, into a single big vertical light box, like a bulletin board. They called that one 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 amoebas 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 Woese gazing intently at those fingerprints, hour upon hour.
“It was routine work, boring, but demanding full concentration,” Woese himself later recalled. Each spot represented a small string of RNA letters — like the letters of the DNA code, A, C, G, T, but with U replacing the T. The shortest useful fragments were at least four letters long, and no more than about 20. Each film, each fingerprint, represented ribosomal RNA from a different creature. The sum of the patterns, taking form in Woese’s brain, represented a new draft of the tree of life.
The work was deceptively perilous. Sogin described to me the deliveries of radioactive phosphorus (an isotope designated as P32, with a half-life of 14 days), which amounted to a sizable quantity arriving every other Monday. The P32 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 P32,” he said, tossing that off as a casual memory. “It was crazy. I don’t know why I’m alive today.”
By 1973, the Woese lab had become one of the foremost users of such 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’d walk home from work saying to myself, ‘Woese, you have destroyed your mind again today.’ ”
George Fox, a rangy young man from Syracuse, came to Urbana in 1973 for a postdoctoral position in Woese’s lab. Fox was not a natural experimentalist and had aspirations to work on the “theoretical stuff,” the deep evolutionary analysis of molecular data, alongside Woese himself. Failing initially to persuade Woese of his aptitude for that, Fox was banished back to the lab, set to the tasks of growing radioactive cells and extracting their ribosomal RNA. But he 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, and sole co-author, on the culminating paper in 1977, with its announcement of a “third kingdom” of life.
The paper announcing that revelation, now considered to be among the most important works ever published in microbiology, is known in the professional shorthand as “Woese and Fox (1977).” But the paper’s immediate reception, by the community of biologists who worked on such subjects, was far from universally admiring. Part of the problem was a matter of scientific protocol: Woese’s discovery had been announced in a news release — issued from NASA, one of his grant sources — just as the paper itself appeared. That offended some scientists. Another factor was that Woese lacked facility as an 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, started and stopped, generally failing to inspire or persuade. Then suddenly that November, 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,” according to Ralph Wolfe, a microbiologist and colleague, “he couldn’t communicate with them. Because they didn’t understand his vocabulary.” Wolfe helped with growing these organisms in the lab, though he wasn’t credited (or implicated, depending on your view of it) as a co-author on the controversial paper. “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 Chicago Tribune, for instance, carried a dizzy headline asserting that “Martianlike Bugs May Be Oldest Life.” The news-release approach backfired, the popular news accounts overshadowed the careful scientific 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 Nov. 3, 1977, he recollected in a personal essay, “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 at Illinois during Wolfe’s earlier years, who called now from M.I.T., 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 scientific report, with its supporting data, to which Wolfe referred him. He never called back. But the broader damage was done. After Luria’s call and others, Wolfe added, “I wanted to crawl under something and hide.”
To me, during a chat in his office, Wolfe said: “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 15 years.”
Woese’s ideas eventually found purchase in Europe, and in time, scientists in the United States recognized him as well. In 1984 Woese received a MacArthur Fellowship for his efforts in phylogenetic analysis and his discovery of the archaea, and in 1988 he was elected to the National Academy of Sciences. Despite the MacArthur honor, and because the Academy had elected him relatively late (at 59), he still thought of himself as a neglected outsider. That gave him some latitude to continue being ambitious, bold and ornery. And he wanted to revisit the status of his beloved archaea.
As an outlet for this work, Woese turned to the Proceedings of the National Academy of Sciences, a journal in which — as a member now of the Academy — he could be a bit more speculative than he would at Nature or Science. His next big paper, published in June 1990 with two co-authors and titled “Towards a Natural System of Organisms,” made several main assertions. First, any system of classification should be strictly “natural,” as the title suggested — meaning phylogenetic, reflecting evolutionary relationships. Second, there should be three major divisions of life, not two (the predominant view), not five (an alternative proposal, recognizing animals, plants, bacteria, fungi and a catchall group of other eukaryotes), and those divisions should be known as domains. Three domains, recognized above the old kingdoms rather than replacing them: It was ingenious strategically, transcending rather than rejoining the battle over kingdoms.
Last of the paper’s main points was that these three domains should henceforth be known as the Bacteria, the Eucarya (now known as Eukarya, a better transliteration of the Greek roots, meaning “true kernel,” because of the cell nucleus) and the Archaea. And of course there was a tree. It was drawn in straight, simple lines, but it was rich and provocative nonetheless.
It was the last of the great classical trees, authoritative, profound, completely new to science and correct to some degree. But it only served as a point of departure for what came next.
The following decade saw an explosive recognition of the bizarre, counterintuitive phenomenon called horizontal gene transfer and the role it has played throughout the history of life. That explosion occurred during the 1990s but had deep precedents, even before Woese’s work opened the door to appreciating its unimaginable prevalence and significance.
The first recognition by science that any such thing as H.G.T. might be possible dates to 1928, when an English medical researcher named Fred Griffith first detected a puzzling transformation among the bacteria that cause pneumococcal pneumonia: one strain changing suddenly into another strain, presto, from harmless to deadly virulent. At the Rockefeller Institute in New York during the 1940s, Oswald Avery and two colleagues identified the “transforming principle” in such instantaneous transmogrifications as naked DNA — that is, genes, moving sideways, from one strain of bacteria into another. To say that seemed odd is an understatement. Genes weren’t supposed to move sideways; they were supposed to move vertically, from parents to offspring — even when the “parents” were bacteria, reproducing by fission. But by 1953, the great Joshua Lederberg, then at the University of Wisconsin, had shown that this sort of transformation, relabeled “infective heredity,” is a routine and important process in bacteria. Still more unexpectedly, as later work would reveal, H.G.T. is not unique to bacteria.
Slowly at first, during the 1980s and early 1990s, H.G.T. became a favored research focus in more than a few labs. Many researchers had followed Woese’s lead, using ribosomal rRNA as the basis for comparing one organism with another, judging relatedness and constructing trees of life. But then, as new tools and methods made gene sequencing easier and faster, and as more powerful computers allowed analysis of the vast troves of genomic data, researchers went far beyond 16S rRNA, comparing other genes and whole genomes. What they found surprised them: that many genes had moved sideways from one lineage of life into another. Such genes might be absent from most living species within a group (say, a family of butterfly species), implying that it was absent too from the common ancestral form, but it might show up unexpectedly in one species of butterfly in that family, matching closely to a gene that exists only in another kind of creature (say, a bacterium), classified to an entirely different part of the tree of life. How could that happen? If the gene was absent from the common ancestor, it couldn’t have gotten into the anomalous butterfly species by vertical descent.
Researchers have identified three primary mechanisms by which H.G.T. occurs, each of which has a formalized label: conjugation, transformation and transduction. Conjugation is sometimes loosely called “bacterial sex.” It occurs when two individual bacteria (they needn’t be of the same species) form a copulation-like connection, and a segment of DNA passes from one to the other. (It’s isn’t really bacterial sex because it involves gene exchange but not reproduction.) Transformation is what Fred Griffith noticed in 1928: uptake of naked DNA, left floating in the environment after the rupture of some living cell, by another living cell (again, not necessarily of the same species). Transduction is a sort of drag-and-drop trick performed by viruses, picking up bits of DNA from cells they infect, then dropping those DNA bits later within other infected cells, where they may become incorporated into the genomes.
Conjugation was known to be widespread and common among bacteria. H.G.T. by transformation and transduction could potentially occur among other creatures too, even eukaryotes — even animals and plants — though that prospect was far more uncertain and startling, into the 1990s and beyond. Then improved genome sequencing and closer scrutiny brought more surprises. A bacterium had sent bits of its DNA into the nuclear genomes of infected plants. How was that possible? A species of sea urchin seemed to have shared one of its genes with a very different species of sea urchin, from which its lineage diverged millions of years earlier. That was a stretch. Still another bacterium, the familiar E. coli, transferred DNA into brewer’s yeast, which is a fungus. Brewer’s yeast is microbial, a relatively simple little creature, but nonetheless eukaryotic. This mixing of fungal host and bacterial genes happened via a smooching process that looked much like bacterial transformation, the researchers reported, and “could be evolutionarily significant in promoting trans-kingdom genetic exchange.” Trans-kingdom is a long way for a gene to go.
New investigations, as time passed and improvements in gene-sequencing technology made more complete genomes available, showed that far more radical leaps were happening, and not infrequently. For instance: There’s a peculiar group of tiny animals known as rotifers, once studied only by invertebrate zoologists but now notable throughout molecular biology for their “massive” uploads of alien genes. Rotifers are homely beyond imagining. They live in water, mainly freshwater, and in moist environments such as soils and mosses, rain gutters and sewage-treatment tanks. Some species favor harsh, changeable environments that sometimes go dry, and their individuals reproduce without sex. Despite the absence of sexual recombination, which shuffles the genetic deck in a population and offers new combinations of genes, these rotifers have managed to find newness by other means. One means is horizontal gene transfer. Three researchers at Harvard and Woods Hole sequenced portions of the genome of a certain rotifer and found all sorts of craziness that shouldn’t have been there. More specifically, they found at least 22 genes from other creatures, most of which, they concluded, must have arrived by H.G.T. Some of those were bacterial genes, some were fungal. One gene had come from a plant. At least a few of those genes were still functional, producing enzymes or other products useful to the rotifer.
Some of these individual cases were later challenged, but the trend of discoveries held. H.G.T. also started showing up among insects. Again this was supposed to be impossible. There were fervent doubters. Alien genes cannot move from one species to another, they insisted. The germ line of animals, meaning the eggs and the sperm and the reproductive cells that give rise to them, is held separate from such influences. It’s sequestered behind what biologists call the Weismann barrier, named for August Weismann, the German biologist of the 19th and early 20th centuries who defined the concept. Bacteria cannot cross that barricade, the Weismann barrier — so said the skeptical view — to insert bits of their own DNA into animal genomes. Impossible. But again it turned out to be possible.
Beyond the realm of insects and rotifers, evidence of H.G.T. has even been found in mammals — an opossum from South America, a tenrec from Madagascar, a frog from West Africa, all carrying long sections of similar DNA that seem to have come to them sideways, by some sort of infection. “Infective heredity” again. Even the human genome has been laterally invaded. Its sequencing has revealed the boggling reality that 8 percent of our human genome consists of viral DNA inserted sideways into our lineage by retroviruses. Some of those viral genes, as illuminated by a French scientist named Thierry Heidmann and his colleagues, have even been co-opted to function in human physiology, such as creating an essential layer between the placenta and the fetus during pregnancy.
These and other discoveries of H.G.T. had an impact on evolutionary thinking. One form of that impact, like the blade of an ax, was on the very idea of the tree — and particularly on the tree as Woese had drawn it, using ribosomal RNA as the definitive signal of life’s ever-diverging history. Other researchers began offering other images of evolutionary history, other “trees,” some of them not very treelike, that took account of H.G.T. and represented those entanglements of evolutionary history. Among the most vivid was one drawn by Ford Doolittle, an American biologist at Dalhousie University in Halifax, Nova Scotia, who had known Woese during Doolittle’s years as a postdoc in Urbana. In a review article for Science in 1999, Doolittle offered his own hand-drawn cartoon as an alternative to Woese’s three-limb tree. Doolittle called his “a reticulated tree,” but it suggested also a tangle of pipes in someone’s basement, set in place by a manic plumber.
Maybe, Doolittle said in his text, as well as with his drawing, the history of life just can’t be shown as a tree.
Ford Doolittle’s reticulated tree.
Carl Woese, as his research career ended, assumed his new role as a much-honored but cranky elder, with strong opinions. He collected kudos, and he wrote. Having already received a MacArthur and an award from the National Academy of Sciences and the Leeuwenhoek Medal (microbiology’s highest honor) from the Royal Netherlands Academy of Arts and Sciences, in 2000 he was announced as a winner of the National Medal of Science, bestowed by the president of the United States with advice from scientific counselors. Woese declined to attend the event in Washington because, according to a friend, he didn’t want to shake Bill Clinton’s hand. In 2003 came the Crafoord Prize, given by the Royal Swedish Academy of Sciences as a complement to the Nobel Prizes and presented by Sweden’s king. Woese hated travel, but he did go to Stockholm for that event and had no scruples about shaking the hand of King Carl XVI Gustaf. The Crafoord was gratifying, but he seems to have yearned for more. Woese had been nominated for a Nobel, but maybe his discovery of the archaea seemed a little too obscure, and maybe he just didn’t live long enough.
Woese had a sort of bifurcated brain, one of his oldest friends, Larry Gold, told me. Gold, now a distinguished molecular biologist and biotech entrepreneur, knew Woese from the early days in Schenectady when they both worked for G.E., and remained close to him through the years. On one side of Woese, he said, was this great depth of learning — mostly acquired by self-instruction, not formal training — and a relentless questioning. Woese had trained at Yale as a biophysicist, Gold reminded me, not a biologist. “He didn’t know any biology. He knew less biology by the time he died than I know,” Gold said self-deprecatingly. “That’s a terrible thing to say. But he didn’t really think about biology. He was thinking about what happened 3.5 billion years ago. That’s not biology.” It’s more a gumbo of physics and molecular evolution and geology, Gold meant. But the deep history, going back those billions of years, lay at the core of understanding evolution, as Woese tried to do it.
One year after the Crafoord Prize, in 2004, he published another of his big, ambitious treatises. This appeared not in Nature or Science but in a narrower journal, Microbiology and Molecular Biology Reviews, the editors of which allowed him 14 pages to vent. It was an appropriate outlet, not just a spacious one, because he wanted to tell the field of molecular biology just what he thought of it. He wanted to piss in the punch bowl.
He titled this essay “A New Biology for a New Century.” His central point was that molecular biology had strayed from its early promise and declined to “an engineering discipline.” By that he meant it had come to concern itself with applications, such as genetic modification of organisms for agriculture or environmental remediation, and the concerns of human health, rather than the fundamental questions about how life had arisen, become complex and evolved for billions of years. Worse, molecular biology took a “reductionist” perspective on what it saw as mechanistic problems, Woese argued, such as the workings of the gene and the cell. It lost sight of “the holistic problems” of evolution, life’s ultimate origins and the deepest mysteries of how life-forms became organized. It lost interest, or never had any, in the big story over four billion years.
“How else could one rationalize the strange claim,” Woese wrote, “by some of the world’s leading molecular biologists (among others) that the human genome (a medically inspired problem) is the ‘Holy Grail’ of biology? What a stunning example of a biology that operates from an engineering perspective, a biology that has no genuine guiding vision!” A science like that, intent on changing the living world without trying to understand it, he added, “is a danger to itself.”
No one ever accused Woese of pulling his punches. And as he got older, ever more pugnacious, he harbored an increasing disdain for Charles Darwin, distinct from but alongside his disdain for molecular biology. The Darwin animus had kindled within him, an off-and-on resentment of the distant figure with the big name. Part of it might have been substantive disagreement: Darwin himself, and the neo-Darwinian synthesis of ideas that became orthodoxy during the 20th century, saw evolutionary change as inherently incremental and gave little attention to the processes of inheritance, variation and reproduction as they occur among microbes, as opposed to animals and plants. Woese saw microbial evolution and (later in his life) H.G.T. as essential to understanding deep history, eons before the time, the threshold, when Darwin’s vision became relevant. Another part was probably sheer jealousy. He came to believe himself a more important, more profound and more revolutionary thinker than Darwin himself.
Woese was bitter and needy toward the end of his life. But he was also a great scientist, one of the greatest, if not Darwin’s peer as a visionary of evolution’s mysteries.
Among the essential points of the upheaval that Woese helped initiate are three counterintuitive insights, three challenges to categorical thinking about aspects of life on earth. The categoricals are these: species, individual, tree. Species: It’s a collective entity but a discrete one, like a club with a fixed membership list. The lines between this species and that one don’t blur. Individual: An organism is also discrete, with a unitary identity. There’s a brown dog named Rufus; there’s an elephant with extraordinary tusks; there’s a human known as Charles Robert Darwin. No mixing refutes the oneness of an individual. Tree: Inheritance flows always vertically from ancestor to descendant, always branching and diverging, never converging. So the history of life is shaped like a tree.
Now we know, thanks to Carl Woese and those who have followed him, that each of those three categoricals is wrong.
In the early summer of 2012, while vacationing with his wife on Martha’s Vineyard, Woese became ill — an intestinal blockage. It was pancreatic cancer. He sent for his trusted administrative assistant and friend, Debbie Piper, to join him and his family. She flew into Boston, and he pleaded with her to rescue him from Massachusetts General Hospital and the mind-dulling medication he was given after surgery. He wanted clarity more than he wanted comfort. Piper and Woese’s daughter helped get him aboard a medical charter flight and back to Urbana.
That August, he consented to endure a series of video interviews for the historical record. Several friends came to town for that purpose, to assist in the questioning, and Woese did his best to respond, with halting reflections on his work, his discoveries, the science of his time.
Pale and manifestly uncomfortable, seated before bookshelves and an ivy plant, he spoke to the camera for seven hours spread across three days, laboring to remember facts and names, to express ideas, frustrated when he was unable to. There was so much that still needed saying. Now it was too late. He took long pauses. He blinked back his own mortality. At one point he said, “My memory serves badly, badly, badly.” The camera captured it all. At the time of his memorial service, months afterward, someone raised the idea of playing some of this video to bring his voice and image into the event.
Piper, when we spoke, recalled her reaction to that thought: “Oh, please don’t. Because he just looks and sounds like a sick old man.”
But inside the sick old man was a multiplicity of other realities. Some had arisen straight, and some had arrived sideways.
This article is adapted from “The Tangled Tree: A Radical New History of Life,” published by Simon & Schuster.
David Quammen is an author and a three-time recipient of the National Magazine Award.
Sign up for our newsletter to get the best of The New York Times Magazine delivered to your inbox every week.
A version of this article appears in print on Aug. 19, 2018, on Page 34 of the Sunday Magazine with the headline: Scrambling Darwin. Order Reprints | Today’s Paper | Subscribe
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.