The Tangled Tree

by David Quammen

  “Who coined the name?” I asked Feschotte.

  “I did. You know, I do the marketing. They do the work.” We both laughed at his professorial self-deprecation. “I coin the names of the elements,” he said, still in joke mode about these crucial scientific chores: “I talk to the reporters and the writers.”

  Furthermore, he reminded me, these genomes of the tenrec and the opossum and the rest—they were all publicly available through an online database. In the current era, happily for science, people sequence whole genomes and share them. “This is the most democratic kind of research. Anybody could have found this at any time,” Feschotte said. “You just need an internet connection, and you can do it.” You can do it, that is, if you have that connection plus the biological knowledge and computational skills to ask the right questions in the right ways. But it’s harder than Facebook. The paper on this work appeared in 2008, and John K. Pace II, the unassuming guy who just wanted a master’s degree, left UT-Arlington with a PhD.

  Among the big unknowns about all these transposons, intriguing to Feschotte, are (1) where they come from originally, (2) how they enter a new genome, and (3) why they copy themselves so profusely once they have gotten aboard. None of those three questions can be answered with certainty, but Feschotte has his preferred guesses. On the third, the matter of their busy self-copying, he favors the surplus DNA concept (non-gene DNA whose only “purpose” is to survive and proliferate) mentioned by Richard Dawkins in The Selfish Gene, his 1976 bestseller, and developed further by Ford Doolittle and a grad student in a 1980 paper. By this logic, transposons have acquired the capacity to self-copy because it improves their prospects of long-term survival. They replicate themselves more quickly than the host genome replicates, and they sometimes jump into other lineages, which enables them to evade extinction with the dying out of a single lineage. As a secondary effect, the redundant DNA that they add to a genome becomes available and might even prove useful, as it mutates, for cellular functions.

  Gene regulation, for instance. That’s how Barbara McClintock construed her transposons. Ultimately this may give the host organisms some survival advantage, and if the host lineage survives extinction, the transposon survives too. For the meantime, though, there was no proof of this. It was just McClintock’s hypothesis.

  The first unknown of Cedric Feschotte’s three (ultimate source of any given transposon) remains mysterious, but on the second (mode of arrival), he has some ideas: parasites and infection. Viruses may occasionally carry such bits of selfish DNA from one species to another, just as viruses sometimes carry whole genes in the process of HGT. The parallel is close enough that Feschotte and his team began calling the process horizontal transposon transfer (HTT). That can be considered a subcategory of HGT. And they found evidence implicating one particular parasitic insect (Rhodnius prolixus) in cases of transposon transfer. It’s a mean little critter, this insect, native to South America and Central America, that feeds on the blood of birds, reptiles, and mammals, including humans. It belongs to the group known as kissing bugs, because they tend to bite in the area near a victim’s mouth.

  Kissing bugs are despised in the American tropics not just for biting but also for their role in transmitting Chagas disease, a lingering and sometimes fatal affliction caused by a protozoan that replicates in a victim’s blood and tissues. Charles Darwin encountered kissing bugs in Argentina during the Beagle voyage, when he made a horseback jaunt inland and slept in a bug-ridden village. He recorded in a notebook that it was “horribly disgusting, to feel numerous creatures nearly an inch long & black & soft crawling in all parts of your person—gorged with your blood.” Typical of Darwin, when he was still young and robust, he shrugged that off with the aside “good to experience everything once.” Whether the kissing bugs gave him Chagas disease is unknowable now (short of exhuming him from the floor of Westminster Abbey), but Chagas has been one hypothesis for the mysterious, chronic illness that punished Darwin throughout his middle years.

  It turns out that this kissing bug, Rhodnius prolixus, carries more than the Chagas protozoan in its belly. Like the tenrec and the opossum and the frog of John Pace’s study, it carries also a hefty dose of transposons in its genome. That genome was available—sequenced by others, presumably because of medical interest in Chagas disease—and Feschotte himself made the transposon discovery, he told me, while “messing around at home one night.” By “messing around,” he meant scanning a large number of published genomes, using sophisticated bioinformatics tools, to see where Space Invaders might turn up. He found it, unexpectedly, in the kissing bug. He already knew from the work with John Pace of its presence in several species of mammal, including the opossum, one of the bug’s preferred South American hosts. That raised his suspicion, given the bug’s blood-sucking habits, which seemed to offer opportunity for transfer of DNA as well as disease. It suggested that the bug might be an intermediary, a vector, for the transposon. Next morning, he alerted two of his postdocs and invited them to investigate. Further scanning the bug’s genome, they found not just Space Invaders, represented in more than two hundred copies, but also three other transposons known previously in mammals. From the evidence of mutation rates, the transfers seemed to have happened within a time range of fifteen million to forty-six million years ago.

  Let’s pause briefly to appreciate just how odd this scenario is: selfish DNA passing from the genome of one species of mammal, through the belly of a blood-sucking insect, into another species of mammal, where it inserts itself into that genome. The transposed DNA becomes part of the second mammal’s heritable legacy. And once the self-copying of the transposon begins, it adds masses of DNA to the genome. This could be bad or, much less probably, good. If bad, it disarranges the genome, destroys necessary gene functions, induces congenital diseases, and maybe even causes the mammal lineage to go extinct. Science will never see that transposon, because it has vanished with the unlucky lineage. But if the mammal is lucky, the new DNA brings no mortal harm, and some of it could even become useful. It adds possibility, it adds raw genetic material, it adds the chance of new genes taking shape from old transposon DNA. And new genes, as environments change, can mean the difference between survival and oblivion. If a new gene is distinctly valuable, it spreads through the population, it passes the test of time, and it enshrines itself in a lineage of opossums or monkeys or frogs or other creatures, such that Cedric Feschotte’s group might find it there many millions of years later. Meanwhile, it could alter the course of evolution.

  Including human evolution. Back in 2007, in a slightly different effort, John Pace and Cedric Feschotte assembled a list of transposons that have entered the primate lineage, most likely by horizontal transfer, over the past eighty million years. They found forty. Each has copied itself abundantly. Those copies now constitute about 98,000 distinct elements, 98,000 stretches of alien DNA, amounting to 1 percent of the human genome. They’re still with us, changing slowly, and their effects too are largely unknown.

  76

  As his research career ended, Carl Woese assumed his new role as a much-honored but crotchety elder with strong opinions. He collected kudos, and he wrote. Having already received a MacArthur Fellowship, and an award from (in addition to his election to) 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 attended the event in Washington because 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, inviting Harris Lewin and Gary Olsen (his faithful collaborator in Urbana) to accompany him, and he had no scruples about shaking the hand of King Carl XVI Gustaf. The C
rafoord Prize is sometimes split between awardees (Edward O. Wilson and biologist Paul Ehrlich shared it in 1990), but Woese got it all, the $500,000 and the honor. “For Carl, winning the Crafoord Prize by himself was a tremendous vindication,” Lewin wrote later, “and he joked that winning the Crafoord alone (especially without Craig Venter) was better than sharing a Nobel.” Brave talk, but even Lewin didn’t believe him. “In reality, I am certain that Carl coveted a Nobel Prize.” He could console himself with the rationale that the Nobels recognize no biology category, but Barbara McClintock received one in the category Physiology or Medicine, for biological work, and so did Watson and Crick. 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.

  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 fifteen 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 failed 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. Woese, for his part, wasn’t nearly so interested in human health as in evolution. Back at the dawn of the molecular era—when Oswald Avery discovered transformation, when Watson and Crick solved the structure of DNA, when Crick suggested “protein taxonomy” as a way to discern the tree of life, when Zuckerkandl and Pauling proposed using molecules as an evolutionary clock—back in that glorious time, molecular biology had seemed a branch of science that might illuminate “the master plan of the living world.” But then came a schism. Two biologies: molecular went one way, and evolutionary went another. Academic biology became divided, in universities all over America and much of the world. Two separate curricula, two separate buildings.

  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!”

  No one ever accused Woese of pulling his punches. And as he got older, ever more pugnacious, his disdain for Charles Darwin rose too, distinct from but alongside his disdain for molecular biology. The Darwin animus had kindled within him for a long time, other testimony suggests, but in impersonal and inconsistent form, an off-and-on resentment of the distant figure with the big name. According to his friend Nigel Goldenfeld, Woese never read On the Origin of Species until around 2000, because he presumed it irrelevant to the evolutionary questions that interested him. What he knew of Darwin’s theory, he knew (as most people, even biologists, know that theory) from secondary sources. Then he did read The Origin and a bit of Darwin’s other work, and at first he reacted favorably. In 2005, responding to an interviewer’s question about scientists who had inspired him, he mentioned Crick, Fred Sanger, and just a few others, including Darwin, “whose writings I encountered rather late in the game, but increasingly turn to as my foray into evolution deepens. How could he have been so right about so much? Astounding!” That interview appeared in Current Biology, a serious journal. He was on record.

  But then something happened, something that radically changed his view of Darwin, or maybe just his bluntness in expressing it. He read Darwin’s Origin more carefully—in fact, he pored through it, comparing the first edition with all five others variously revised by Darwin himself, according to Nigel Goldenfeld, who performed this exercise with Woese. He read the surviving correspondence between Darwin and Alfred Russel Wallace, the man with whom Darwin shared credit in 1858 for conceiving the idea of natural selection. Some of that correspondence bore on the question, persistently argued by several scholars, of whether Darwin seized an undue share of the credit. At their most extreme, those scholars charge that Darwin stole parts of his theory from Wallace and concealed the dastardly deed. It’s a provocative accusation, with all the enticements of good slander, but its credibility evaporates (in my view) with a thorough reading of the Darwin-and-Wallace literature, which is abundant. Woese came to feel differently.

  He also learned about precursors to Charles Darwin—such as Lamarck; Edward Blyth, an English zoologist working in India; and Darwin’s own grandfather, Erasmus Darwin—who had offered inchoate notions of evolutionary change, or partial versions of what Darwin put together so effectively, and to Woese, it all began to look like high intellectual larceny. His dark view was affirmed (if not triggered) by a book titled The Darwin Conspiracy, a tendentious little volume accusing Darwin of plagiarism and deceit. The author was a onetime BBC producer named Roy Davies. Its subtitle: Origins of a Scientific Crime.

  Discovering the Davies book, Woese took it as revelatory. He befriended Davies, ordered multiple copies, and gave them away. There are kernels of fact and circumstance in the Darwin-stole-from-Wallace narrative sufficient to persuade the credulous and it makes a piquant tale. The surprising thing in Woese’s case is that such a deep thinker on other matters would be relatively shallow on this. During the last phase of his life, that piquancy seems to have helped soothe his own frustrations like a menthol lozenge.

  Mostly he expressed his grudge against Darwin in private to friends and colleagues. On February 12, 2009, Darwin’s two hundredth birthday, for instance, Woese noted the date by sending select friends a terse message: “Let this be a day of rage.” He began work on a book with Jan Sapp, under the title Beyond God and Darwin, which Sapp conceived as a sort of popularized version of his superb but dense tome The New Foundations of Evolution. This new book would offer a streamlined account of the revolution in molecular phylogenetics, showing that the discoveries of Woese and some of his colleagues transcended Darwinian theory, and did it without giving any support to creationist ideology. That was the point of Sapp’s intended title. Such discoveries—of endosymbiosis, horizontal gene transfer, and the deeply contorted tree of life—go beyond the God-versus-Darwin dichotomy, beyond creationism versus The Origin. They go beyond Darwinian theory without undermining the reality of evolution.

  Sapp wrote an introduction and sent it to Woese for comment. To this draft, Woese added his annotations in upper case, which gave the impression of a stern editor. “SHARPEN UP,” Woese typed after one paragraph. “MORE PUNCHY.” Most of the comments were small quibbles and wording suggestions. But at the end of the draft, Woese wrote: “JAN, YOU ACCORD DARWIN SO MUCH MORE SUBSTANCE THAN THE BASTARD DESERVES.”

  Sapp dropped the project not long after this exchange, and Beyond God and Darwin never got written. Sapp had lost interest in the book effort, though not in the topic, he told me. He was also disheartened by Woese’s increasingly needy ego. “Later in life, Carl thought he was bigger than life.”

  “And bigger than Darwin,” I suggested.

  We were discussing this over lunch in a noisy restaurant in Montreal. Sapp swallowed, let my comment pass, and said, “I didn’t like that side of him.” But their relationship survived to the end, despite Woese’s disappointment about Beyond God and Darwin. Sapp didn’t think Woese actually cared much about finishing the book, he told me later, but that nonetheless Woese might gladly have worked on it fore
ver, because it gave them occasion for so many phone calls and emails, as well as discussion in person. “He was in it for the dialogue.” Woese was a lonely man—though he had a wife and two children in a home just off campus—and he treasured his friends

  This draft introduction with Woese’s inserted comments resides among the Carl Woese Papers at the University of Illinois Archives. Another odd item preserved there (and called to my attention by the archivist John Franch, on the same day he showed me the X-ray films of Woese’s earliest RNA fingerprints) is a cheap ring notebook, its yellow cover fading to cream, bought from a CVS pharmacy some time after 2006. It’s unlabeled and untitled, but it contains a few pages of cursive scribble in Woese’s hand. One page holds a single line, “Book 1: Growing up in Science,” suggesting he may have intended an autobiography. The next page, headed “Preface,” dates to the period of bicentennial celebrations of Charles Darwin’s birth (just following the world financial crisis of 2008), when Woese hit his peak of disgruntlement.

  Darwin was born, as I’ve mentioned, on February 12, 1809. “As I set pen to paper,” Woese wrote, “the year is 2009. It’s Darwin, Darwin everywhere and no one with a thought. Hopefully this year will be a nadir in biology—as it (hopefully) is in the world economy, and both biology and the economy will recover.” The few paragraphs that follow are muddled and grumpy, inconclusive ruminations on evolution—“the heart center of biology”—and on the sad fact that society has confused evolutionary biology with Darwinism. The last page of the sequence is mostly crossed out with zigzag lines. One sentence is left to stand: “Science does not succeed by ‘keeping secrets’ and ‘being diplomatic’ (i.e., scheming); that’s alchemy.” The rest of the notebook is empty. The autobiography, like the book with Jan Sapp, never happened.