Sleeping w the Enemy-1

Sleeping w the Enemy-1 - ANNALS OF EVOLUTION SLEEPING WTH...

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Unformatted text preview: ANNALS OF EVOLUTION SLEEPING WTH THE ENEMY VV/yai bappened between time Neandert/Jals and in? BY ELIZABETH KOLBERT “ he Max Planck Institute for Evolu— tionary Anthropology, in Leipzig, is a large, mostly glass building shaped a bit like a banana. The institute sits at the southern edge of the city, in a neighbor— hood that still very much bears the stamp of its East German past. If you walk down the street in one direction, you come to a block of Soviet—style apartment buildings; in the other, to a huge hall with a golden steeple, which used to be known as the Soviet Pavilion. (The pavilion is now empty.) In the lobby of the institute there’s a cafeteria and an exhibit on great apes. A TV in the cafeteria plays a live feed of the orangutans at the Leipzig Zoo. Svante Paabo heads the institute’s de— partment of evolutionary genetics. He is tall and lanky, with a long face, a narrow chin, and bushy eyebrows, which he often raises to emphasize some sort of irony. Paabo’s office is dominated by a life’size model of a Neanderthal skeleton, propped up so that its feet dangle over the floor, and by a larger-than—life—size portrait that his graduate students presented to him on his fiftieth birthday. Each of the students painted a piece of the portrait, the over—all effect of which is a surprisingly good like— ness of Paabo, but in mismatched colors that make it look as if he had a skin disease. At any given moment, Paabo has at least half a dozen research efforts in prog— ress. When I visited him in May, he had one team analyzing DNA that had been obtained from a forty— or fifty~thousand~ year—old finger bone found in Siberia, and another trying to extract DNA from a cache of equally ancient bones from China. A third teamwas slicing open the brains of mice that had been genetically engineered to produce a human protein. In Paabo’s mind, at least, these re— search efforts all hang together. They are attempts to solve a single problem in evo— lutionary genetics, which might, rather dizzyingly, be posed as: What made us r the sort of animal that could create a transgenic mouse? 64 THE NEW YORKER, AUGUST 15 57 22, 20" “‘The challenge is to address the questions The question of what defines the human has, of course, been kicking around since Socrates, and probably a lot longer. If it has yet to be satisfactorily re— solved, then this, Paabo suspects, is be— cause it has never been properly framed. that are answerable,” he told me. Paabo’s most ambitious project to date, which he has assembled an international consortium to assist him with, is an at’ tempt to sequence the entire genome of the Neanderthal. The project is about half— way complete and has alreadyyielded some unsettling results, including the news, an— nounced by Paabo last year, that modern humans, before doing in the Neanderthals, must have interbred with them. Once the Neanderthal genome is com— plete, scientists will be able to lay it gene by gene—indeed, base by base—against the human, and see where they diverge. At that point, Paabo believes, an answer to the age~old question will finally be at hand. Neanderthals were very closely related to modern humans—so closely that we shared our prehistoric beds with them—— and yet clearly they were not humans. Somewhere among the genetic disparities must lie the mutation or, more probably, mutations that define us. Paabo already has a team scanning the two genomes, drawing up lists of likely candidates. “I want to know what changed in fully modern humans, compared with Nean— derthals, that made a diiference,” he said. “What made it possible for us to build up these enormous societies, and spread around the globe, and develop the tech~ nology that I think no one can doubt is unique to humans. There has to be a ge— netic basis for that, and it is hiding some— where in these lists.” aabo, who is now fifty—six, grew up in Stockholm. His mother, a chemist, was an Estonian refugee. For a time, she worked in the laboratory of a biochemist named Sune Bergstrom, who later won a Svam‘e Pddbo’s genome—sequencingpmject ATELIER DAYNES; PHOTOGRAPH: 5. ENTRESSANGLE 1g PTO/351‘ [3019470 point up the dzfiéremes that mah/edhumam, unlike the Neanderthals, with whom they interhred, t0 huz'ld complex xocieties. i I 1 i Nobel Prize. Paabo was the product of a lab affair between the two, and, although he knew who his father was, he wasn’t supposed to discuss it. Bergstrom had a wife and another son; Paabo’s mother, meanwhile, never married. Every Satur— day, Bergstrom would visit Paabo and take him for a walk in thewoods, or somewhere else where he didn’t think he’d be recognized. “Ofiicially, at home, he worked on Sat— urday,” Paabo told me. “It was really crazy. His wife knew. But they never talked about it. She never tried to call him at work on Saturdays.” As a child, Paabo wasn’t particularly bothered by the whole arrangement; later, he occasionally threat- ened to knock on Bergstrom’s door. “I would say, ‘You have to tell your son—— your other son—because he will find out sometirne,’ ” he recalled. Bergstrom would promise to do this, but never followed through. (As a result, Bergstrom’s other son did not learn that Paabo existed until shortly before Bergstrom’s death, in 2004.) From an early age, Paabo was inter— ested in old things. He discovered that around fallen trees it was sometimes pos— sible to find bits of pottery made by pre— historic Swedes, and he filled his room with potsherds. When he was a teen— ager, his mother took him to visit the Pyramids, and he was entranced. He en— rolled at Uppsala University, planning to become an Egyptologist. “I reallywanted to discover mummies, like Indiana Jones,” he said. Mostly, though, the coursework turned out to in— volve parsing hieroglyphics, and instead of finding it swashbuckling Paabo thought it was boring. Inspired by his fa— ther, he switched first to medicine, then to cell biology. In the early nineteen—eighties, Paabo was doing doctoral research on viruses when he once again began fantasizing about mummies. At least as far as he could tell, no one had ever tried to obtain DNA from an ancient corpse. It occurred to him that if this was possible, then a whole new way of studying history would open up. Suspecting that his dissertation adviser would find the idea silly (or worse), Paabo conducted his mummy research in secret, at night. With the help of one of his for— ~ mer Egyptology professors, he managed to obtain some samples from the Egyptian . Museum in what was then East Berlin. In 1984, he published his results in an ob— scure East German journal. He had, he wrote, been able to detect DNA in the cells of a mummified child who’d been dead for more than two thousand years. Among the questions that Paabo thought mummy DNA could answer were what caused pharaonic dynasties to change and who Tutankhamun’s mom was. While Paabo was preparing a version of his mummy paper for publication in English, a group of scientists from the University of California at Berkeley an— nounced that they had succeeded in se— quencing a snippet of DNA from a ze— bralike animal known as a quagga, which had been hunted to extinction in the eighteen—eighties. (The DNA came from a hundred~and—forty—year-old quagga hide preserved at the National History Museum in Mainz.) The leader of the team, Allan Wilson, was an eminent bio— chemist who had, among other things, come up with a way to study evolution using the concept of a “molecular clock.” Paabo sent Wilson the galleys of his mummy paper. Impressed, Wilson re— plied asking if there was any space in Paa— bo’s lab; he might like to spend a sabbat— ical there. Paabo had to write back that he could not offer Wilson space in his lab, because, regrettably, he didn’t have a lab—or even, at that point, a Ph.D. Paiibo’s mummy paper became the cover article in Nature. It was also written up in the Times, which called his achieve— ment “the most dramatic of a series of re— cent accomplishments using molecular biology.” Paabo’s colleagues in Sweden, though, remained skeptical. They urged him to forget about shrivelled corpses and stick to viruses. “Everybody told me that it was really stupid to leave that important area for something which looked like a hobby of some sort,” he said. Ignoring them, Paabo moved to Berkeley, to work for Wilson. “He just kind of glided in,” Mary— Claire King, who had also been a student of Wilson’s, and who is now a professor of genome sciences at the University of Washington, recalled. According to King, Paabo and Wilson, who died in 1991, turned out to share much more than an interest in ancient DNA. “Each of them thought of very big ideas,” she told me. “And each of them was very good at translating those ideas into testable hypotheses. And then each of them was very good at developing the 466 THE New YORKER, AUGUST :5 a 22, 20“ technology that’s necessary to test the hy— potheses. And to have all three of those capacities is really remarkable.” Also, al— though “theywere both very data—driven, neither was afraid to say outrageous things about their data, and neither was afraid to be wrong.” DNA is often compared to a text, a comparison that’s apt as long as the definition of “text” encompasses writing ‘ that doesn’t make sense. DNA consists of molecules known as nucleotides knit to— gether in the shape of a ladder—~the fa— mous double helix. Each nucleotide con— tains one of four bases: adenine, thymine, guanine, and cytosine, which are desig— nated by the letters A, T, G, and C, so that a stretch of the human genome might be represented as ACCTCCTC— TAATGTCA. (This is an actual se— quence, from chromosome 10; the com- parable sequence in an elephant is ACCTCCCCTAATGTCA.) The human genome is three billion bases—or, really, base pairs——long. As far as can be determined, most of it is With the exception of red blood cells, every cell in an organism contains a com— plete copy of its DNA. It also contains many copies——hundreds to thousands—of an abridged form of DNA known as tochondrial DNA, or mtDNA. But as soon as the organism dies the long chains of nucleotides begin to break down. Much of the damage is done in the first few hours, by enzymes inside the creature’s own body. After a while, all that remains is snippets, and after a longer while-how long seems to depend on the conditions of decomposition—these snippets, too, dis— integrate. “Maybe in the permafrost you could go-back five hundred thousand years,” Paabo told me. “But it’s certainly on this side of a million.” Five hundred thou— sand years ago, the dinosaurs had been dead for more than sixty—four million years, so the whole “Jurassic Park” fantasy is, sadly, just that. On the other hand, five hundred thousand years ago modern hu— mans did not yet exist. When Paabo arrived in California, he was still interested in finding a way to use genetics to study human history. He’d discovered, however, a big problem with trying to locate fragments of ancient Egyptian DNA: they look an awful lot like-indeed, identical to—fragments of contemporary human DNA. Thus a sin— t the hy— of those Mso, al— .~driven, rageous ther was a text, a 1g as the ; writing >nsists of knit to— ——the fa— ide con— hymine, 7e desig— 1d C, so genome CCTC- :tual se- he com— thant is i.) The tses——0r, lS can be )od cells, 5 a com— contains mds——0f n as mi— .. But as 1g chains n. Much first few reature’s emains is le—how iitions of too, dis— frost you dousand ,tainly on '6d thou- 1ad been ' million ;” fantasy land, five dem hu— ornia, he ray to use try. He’d lem with ' ancient awful lot ments of ms a sin- gle microscopic particle of his own skin, or of someone else’s, even some long— dead museum curator’s, could nullify months of work. “It became clear that human contami— nation was a huge problem,” he explained. (Eventually, Paabo concluded that the se- quences he had obtained for his original mummy paper had probably been cor— rupted in this way.) As a sort of warmup exercise, he began working on extinct an— imals. He analyzed scraps of mtDNA from giant ground sloths, which disappeared about twelve thousand years ago, and from mammoths, which vanished around the same time, and from Tasmanian tigers, which were hunted to extinction by the nineteen—thirties. He extracted mtDNA from moas, the giant flightless birds that pOpulated New Zealand before the arrival of the Maori, and found that moas were more closely related to birds from Austra- lia than to kiwis, the flightless birds that in- habit New Zealand today. “That was a blow to New Zealand self—esteem,” he re— called. He also probed plenty of remains that yielded no usable DNA, including bones fiom the La Brea tar pits and fossil- ized insects preserved in amber. In the process of this work, P'a'abo more or less invented the field of paleogenetics. “Frankly, it was a problem that I wouldn’t have tackled myself, because I thought it was too difiicult,” Maynard Olson, an emeritus professor at the Uni— versity of Washington and one of the founders of the Human Genome Project, told me. “Paabo brought very high stan- dards to this area, and took the field of ancient DNA study from its ‘Jurassic Park’ origins to a real science, which is a major accomplishment.” “There’s nothing unique about most of science,” Ed Green, a professor of biomo— lecular engineering at the University of California at Santa Cruz who works on the Neanderthal Genome Project, said. “If you don’t do it, somebody else is going to do it a few months later. Svante is one of the rare people in science for whom that is not true. There wouldn’t even be a field of ancient DNA as we know it without him.” “It’s a nice rarity in science when peo— ple take not only unique but also produc- tive paths,” Craig Venter, who led a rival Effort to the Human Genome Project, told me. “And Svante has clearly done both. I have immense respect for him and What he’s done.” While Paabo was living in California, he sometimes went to Germany to visit a woman who was attending graduate school at the University of Munich. “I had many relationships with men, but I also had girlfriends now and again,” he told me. The relationship ended; shortly afterward, the University of Munich offered Paabo an assistant professorship. With no pressing reason to move to Ger— many, he demurred. The offer was in— creased to a fiill professorship: “So then I said, ‘Germany isn’t that bad after all. I’ll go there for a few years.’ ” Paabo was still in Munich several years later when he got a call from the Rhenish State Museum, in Bonn. The museum houses the bones of the first Neanderthal to be identified as such, which was dis— covered in the summer of 1856. What did Paabo think the odds were that he could extract usable DNA? He had no way of determining what kind of shape the bones were in until he dissolved them. “I didn’t know what to tell them, so I said, ‘There’s a five-per—cent chance that it works,’ ” he recalled. A few months later, he received a small chunk of the Neanderthal’s right humerus. he first Neanderthal was found in a limestone cave about forty—five miles north of Bonn, in an area known as the Neander Valley, or, in German, dar Neandertal. Although the cave is gone—the limestone was long ago quarried into building blocks—the area is now a sort of Neanderthal theme park, with its own museum, hiking trails, and a garden planted with the kinds of shrubs that would have been encountered during an ice age. In the museum, Neanderthals are portrayed as kindly, if not particularly telegenic, hu- mans. By the entrance to the building, there’s a model ofan elderly Neander— thal leaning on a stick. He is smiling be— nignantly and resembles an unkempt Yogi Berra. Next to him is one of the museum’s most popular attractions—a booth called the Morphing—Station. For three euros, visitors to the station can get a normal profile shot of them— selves and, facing that, a second shot that has been doctored. In the second, the chin recedes, the forehead slopes, and the back of the head bulges out. Kids love to see themselves—or, better yet, their siblings—morphed into Ne— anderthals. They find it screamingly funny. When the first Neanderthal bones showed up in the Neander Valley, they were treated as rubbish (and almost cer- tainly damaged in the process). The frag— ments——a skullcap, four arm bones, two thighbones, and part of a pelvis—were later salvaged by a local businessman, who, thinking they belonged to a cave bear, passed them on to a fossil collector. The fossil collector realized that he was dealing with something much stranger “Your mot/Jar and I are separating éecause I want w/Jaf’s 5652‘ for the country andyour mot/Jar doesn’t. ” was} ~ man. a...» than a bear. He declared the remains to be traces of a “primitive member of our race.” As it happened, this was right around the time that Darwin published “On the Origin of Species,” and the fragments soon got caught up in the debate over the origin of humans. Opponents of evolu— tion insisted that they belonged to an or— dinary person. One theory held that it was a Cossackwho had wandered into the re— gion in the tumult following the Napole- onic Wars. The reason the bones‘looked odd——Neanderthal femurs are distinctly bowed—~was that the Cossack had spent too long on his horse. Another attributed the remains to a man with rickets: the man had been in so much pain from his disease that he’d kept his forehead perpet~ ually tensed-hence the protruding brow ridge. (What a'man with rickets and in constant pain was doing climbing into a cave was never really explained.) Over the next decades, bones resem— bling those from the Neander Valley—- thicker than those of modern humans, with strangely shaped skulls—~were dis— covered at several more sites, including two in Belgium and one in France. Mean— while, a skull that had been unearthed years earlier in Gibraltar was shown to look much like the one from Germany. Clearly, all these remains could not be ex— plained by stories of disoriented Cossacks or rachitic spelunkers. But evolutionists, too, were perplexed by them. Neander- thals had very large skulls—~1arger, on av- erage, than people today. This made it hard to fit them into an account of evolu— tion that started with small—brained apes and led, through progressively bigger brains, up to humans. In “The Descent of Man,” which appeared in 1871, Darwin mentioned Neanderthals only in passing. “It must be admitted that some skulls of very high antiquity, such as the famous one of Neanderthal, are well developed and capacious,” he noted. In 1908, a nearly complete Neander- thal skeleton was discovered in a cave near La Chapelle~auX-Saints, in southern France. The skeleton was sent to a pale— ontologist named Marcellin Boule, at Paris’s National Museum of Natural His- tory. In a series of monographs, Boule in- vented what might be called the cartoon version of the Neanderthals——bent- kneed, hunched over, and brutish. Nean— derthal bones, Boule wrote, displayed a 68 THE NEW YORKER, AUGUST I5 6: 22, 20“ CAGALOGLU From the cistern in the dome the daylight drips While the calls to prayer From the quarter’s seven minarets——— Overlapping tape loops of Submission—~slip Down through the arching crescent lunettes Cut into the air . ' As if the vault itselfhad loosened its grip. I am on my back, listening to the tattoo Of clogs crisscrossing The sopping white marble floor inlaid With veins of still darker matters to pursue. A skittish gleam accents, like eyeshade, A fountain’s boss in The corner alcove, where hot and cold make do In a basin Tony Curtis and Franz Liszt Both stared into once. (Stardom is a predictable fate: The point is forgotten but somehow still missed.) Gods, whenever they annunciate, Long for romance That ironclad heroes peering through the mist Or mousy adolescent girls both provide. The same unlikely Places——a battlefield or grotto— Are returned to, while again the hollow-eyed Ogle in flagrante devoto And obey, shyly, The scrambled revelations so true-and—tried. Congestive, crotch~scented vapor has congealed Into beads that skid Along suction~knots and shadow—ends Abutting my slab. Eager for an ordeal The illustrated brochure commends As a bath to rid The body of its filth both real and unreal, I have bought their boast, “We make you feel reborn,” For fifty euros. Pinched and idly gestured toward a plinth Two centuries of customers have careworn " To a shallow trough not quite my length, ' I’m forced to burrow - Into a pose much more flagellant than faun. The sodden towel is too heavy now to hold Itself across me— And there is the pasha’s bay window, The shn'velled bulblet, the whole ill-shaped scaifold Of surplus fact and innuendo, From the beer belly To the congenital heart flutter’s toehold. "_ mm : L2w9wssimuwaw - WW ‘ 'W‘ ~ W; ' ‘ M‘ W' ‘ kaxnia’aaw” mas; «y» gm. «may Wm“. . The attendant walks up and down on my back, Pacing the problem, Then kneads, then reams, then applies a foam He scrubs in until it causes an attack Of radiance, the world’s palindrome Suddenly solemn, Suddenly seeming to surrender its knack For never allowing us simply to want What we already Have, or are, or perhaps could have been. His hand signal to get up seems like a taunt. I lie there, my fist under my chin, Senses unsteady, Something gradually, like a tiny font, Coming into focus. I sit up and start To notice small bits Of grit When I run my hand over My chest. But wasn’t this debris the chief part Of the package deal? The makeover And its benefits? In the fog I can’t really see What trademark Schmutz the Oriental Luxury Service Has failed to wash off. So I put it in my mouth and taste Two dank gobbets—salty, glairy and grayish— I should have recognized as the waste That was my old self, A loofah having scraped it from each crevice And bulge, from every salacious thought and deed. Every good one, too. It is the past, not just What is wrong, It is the embarrassments we still breast—feed, That we absent—mindedly so long To shed. A new you, Oneself an innate second person succeeds. How do the saints feel when they fall to their knees, God coming to light? Less ecstatic than ashamed, I fear, Of bodies never worthy of being seized. Encumbered by the weight of a tear, In hopeless hindsight They see all that the flesh can never appease, All that the flesh is obliged to mortify. Here I am laid out, Looking up to Where nothing appears, Hardly wondering Why nothing satisfies And yet saddened that it’s all so clear. Tulip waterspouts Trickle. Reservoirs deep underground reply. ——f D. McClatcby “distinctly simian arrangement,” while the shape of their skulls indicated “the pre— dominance of functions of a purely vege— tative or bestial kind.” Boule’s conclusions were studied and then echoed by many of his contemporaries; the British anthro— pologist Sir Grafton Elliot Smith, for in— stance, described Neanderthals as walking with “a half—stooping slouch” upon “legs of a peculiarly ungra/ceful form.” (Smith also claimed that Neanderthals’ “unattrac— tiveness” was “fiirther emphasized by a shaggy covering of hair over most of the body,” although there was—and still is— no clear evidence that they were In the nineteen—fifties, a pair of anat— omists, Williams Straus and Alexander Cave, decided to reexamine the skeleton from La Chapelle. What Boule had taken for the Neanderthals natural pos— ture, Straus and Cave determined, was probably a function of arthritis. Neander— thals did not walk with a slouch, or with bent knees. Indeed, given a shave and a new suit, the pair wrote, a Neanderthal probably would attract no more attention on a New York City subway “than some of its other denizens.” More recent schol— arship has tended to support the idea that Neanderthals, if not quite up to negotiat— ing the l.R.T., certainly walked upright, with a gait we would recognize moreor less as our own. The version of Neander— " thals offered by the Neanderthal Mu— seum—another cartoon—is imbued with cheerful dignity. Neanderthals are pre— sented as living in tepees, wearing what look like leather yoga pants, and gazing contemplatively over the frozen land— scape. “Neanderthal man was not some prehistoric Rambo,” one of the display tags admonishes. “He was an intelligent individual.” Paabo announced his plan to se— quence the entire Neanderthal ge— nome in July, 2006, just in time for the hundred—and—fiftieth anniversary of the Neanderthals discovery. The an— nouncement was made together with an American company, 454 Life Sciences, which had developed a so—called “high throughput” sequencing machine that, with the help of tiny resin spheres, could replicate tens of thousands of DNA snippets at a time. Both inside and out— side the genetics profession, the plan was Viewed as Wildly ambitious, and the project made international news. “A THE NEW YORKER, AUGUST [5 é 22, 20“ 69 . .: 1",..ch Zing-Inui- ” /m iffj‘a “Iwirb Iliad that kind ofenergy. ” STUDY WITH A LOT or BALLS,” the headline in The Economist declared. By this point, a complete version of the human genome had been published. So, too, had versions of the chimpanzee, mouse, and rat genomes. But humans, chimps, mice, and rats are all living organ— isms, while Neanderthals have been ex— tinct for thousand years. The first hurdle was simply finding enough Nean— derthal DNA to sequence. The chunk of the original Neanderthal that Paabo had received had yielded shreds of genetic in- formation, but nowhere near the quanti— ties needed to assemble—or reassemble—— an entire genome. So Paabo was placing his hopes on another set of bones, from Croatia. (The Croatian bones turned out to have belonged to three individuals, all of them women; the original Neanderthal was probably a man.) Toward the end of 2006, Paabo and his team reported that, using a piece of Croatian bone, they had succeeded in se— quencing a million base pairs‘of the Ne— anderthal genome. (Just like the human genome, the full Neanderthal genome consists of roughly three billion base pairs.) Extrapolating from this, they esti- mated that tocomplete the projectwould take roughly two years and six thousand “runs” on a 454 Life Sciences machine. ~ But later analysis revealed that the million 70 THE NEW YORKER, AUGUST 15 Ev 22, 20" base pairs had probably been contami— nated by human DNA, a finding that led some geneticists to question whether Paabo had rushed to publish results that he should have known were wrong. Meanwhile, subsequent bones yielded a much lower proportion of Neanderthal DNA and a much higher percentage of microbial DNA. (Something like eighty per cent of the DNA that has been se— quenced for the Neanderthal Genome Project belongs to microorganisms and, as far as the project is concerned, is use- less.) This meant the initial estimates of the labor involved in finishing the ge- nome were probably far too low. “There were times when one despaired,” Paabo told me. No sooner would one problem be resolved than another materialized. “It was an emotional roller coaster,” Ed Green, the biomolecular engineer from Santa Cruz, recalled. About two years into the project, a new puzzle arose. Paabo had assembled an international team to help analyze the data the sequencing machines were gen— erating*-essentially, long lists of A’s, T’s, G’s, and Cs. Sifting through the data, one of the members of this team, David Reich, a geneticist at Harvard Medical School, noticed something odd. The Ne— anderthal sequences, as expected, were very similar to human sequences. But they were more similar to some humans than to others. Specifically, Europeans and Asians shared more DNA with Ne— anderthals than did Afiicans. “We tried to make this result go away,” Reich told me. “We thought, This must be wrong.” For the past twenty—five years or so, the study of human evolution has been dom- inated by the theory known in the popular press as “Out of Africa” and in academic circles as the “recent single—origin” or “re— placement” hypothesis. This theory holds that all modern humans are descended from a small population that lived in Af— rica roughly two hundred thousand years ago. (Not long before he died, Paabo’s ad— viser Allan Wilson developed one of the key lines of evidence for the theory, based on a comparison of mitochondrial DNA from contemporary humans.) Around a hundred and twenty thousand years ago, a subset of the population migrated into the Middle East, and by fifty thousand years ago a further subset pushed into Eurasia. As they moved north and east, modern humans encountered Neanderthals and other so—called “archaic humans,” who al— ready inhabited those regions. The mod— ern humans “replaced” the archaic hu— mans, which is a nice way of saying they drove them into extinction. This model of migration and “replacement” implies that the relationship between Neanderthals and humans should be the same for all people alive today, regardless of where they come from. Many members of Paabo’s team sus— pected another case of contamination. At various points, the samples had been han— dled by Europeans; perhaps they had got their DNA mixed in with the Neander— thals’. Several tests were run to assess this possibility. The results were all negative. “We kept seeing this pattern, and the more data we got, the more statistically overwhelming it became,” Reich told me. Gradually, the other team members started to come around. In a paper pub- lished in Science, in May, 2010, they in— troduced what Paabo has come to refer to as the “leaky replacement” hypothesis. (The paper was later voted the journal’s outstanding article of the year, and the team received a twenty—five—thousand— dollar prize.) Before modern humans “re- placed” the Neanderthals, they had sex with them. The liaisons produced chil— dren, who helped to people Europe, Asia, and the New World. The leaky—replacement hypothesis—- assuming for the moment that it is cor— rect—provides further evidence of the closeness of Neanderthals to modern humans. Not only did the two inter- breed; the resulting hybrid offspring were functional enough to be integrated into human society. Some of these hy-‘ brids survived to have kids of their own, who, in turn, had kids, and so on to the present day. Even now, at least thirty thousand years after the fact, the signal is discernible: all non—Africans, from‘the New Guineans to the French to the Han Chinese, carry somewhere between one and four per cent Neanderthal DNA. One of Paabo’s favorite words in English is “cool.” When he finally came around to the idea that Neanderthals be— queathed some of their genes to modern humans, he told me, “I thought it was very cool. It means that they are not totally extinct—-that they live on a little bit in us.” he Leipzig Zoo lies on the opposite side of the city from the Institute for Evolutionary Anthropology, but the in- stitute has its own lab building on the grounds, as well as specially designed test— ing rooms inside the ape house, which is known as Pongoland. Since none of our very closest relatives survive (except as lit- tle bits in us), researchers have to rely on our next closest kin, chimpanzees and bonobos, and our somewhat more distant cousins—gorillas and orangutans—-to perform live experiments. (The same or, at least, analogous experiments are usu— ally also performed on small children, to see how they compare.) One morning, I went to the zoo, hoping to watch an ex- periment in progress. That day, a BBC crew was also visiting Pongoland, to film a program on animal intelligence, and when I arrived at the ape house I found it strewn with camera cases marked “Ani- mal Einsteins.” For the benefit of the cameras, a re— searcher named Hector Marin Manrique was preparing to reénact a series of exper- irnents he’d performed earlier in a more purely scientific spirit. A female orang— utan named Dokana was led into one of the testing rooms. Like most orangutans, she had copper—colored fur and a world— weary expression. In the first experiment, which involved red juice and skinny tubes of plastic, Dokana showed that she could distinguish a functional drinking straw from a non—functional one. In the second, which involved more red juice and more plastic, she showed that she understood the idea of a straw by extracting a rod from a length of piping and using the pipe to drink through. Finally, in a Mensa-level show of pongid ingenuity, Dokana managed to get at a peanut that IVIanrique had placed at the bottom of a long plastic cylinder. (The cylinder was fixed to the wall, so it couldn’t be knocked over.) She fist—walked over to her drink— ing water, took some water in her mouth, fist—Walked back, and spit into the cylin— der. She repeated the process until the peanut floated within reach. Later, I saw this experiment re—staged with some five— year—old children, using little plastic con— tainers of candy in place of peanuts. Even though a full watering can had been left conspicuously nearby, only one of the kids—a girl—managed to work her way to the floating option, and this was after a great deal of prompting. (“How would water help me?” one of the boys asked, just before giving up.) One way to try to answer the question “What makes us human?” is to ask “What makes us diiferent from apesP,” or, to be more precise, from nonhuman apes, since, of course, humans are apes. As just about every human by now knows—fiind as the experiments with Dokana once again confinnflnonhuman apes are extremely clever. They’re capable of making infer- ences, of solving complex puzzles, and of understanding What others are (and are not) likely to know. When researchers from Leipzig performed a battery of tests on chimpanzees, orangutans, and two— and~a—half-year—old children, they found that the chimps, the orangutans, and the kids performed comparably on a wide range of tasks that in- volved understanding of the physical world. For example, if an experimenter placed a re~ ward inside one of three cups, and then moved the cups around, the apes found the goody just as often as the kids—-indeed, in the case of chimps, more often. The apes seemed to grasp quantity as well as the kids did— they consistently chose the dish contain— ing more treats, even when the choice in- volved using what might loosely be called math—and also seemed to have just as good a grasp of causality. (The apes, for instance, understood that a cup that rat— tled when shaken was more likely to con— tain food than one that did not.) And they were equally skillful at manipulating sim— ple tools. v Where the kids routinely outscored the apes was in tasks that involved read— ing social cues. When the children were given a hint about Where to find a re- ward———someone pointing to or looking at the right container—-they took it. The apes either didn’t understand that they were being offered help or couldn’t follow the cue. Similarly, when the children were shown how to obtain a reward, by, say, ripping open a box, they had no trou— ble grasping the point and imitating the behavior. The apes, once again, were flummoxed. Admittedly, the kids had a big advantage in the social realm, since the experimenters belonged to their own species. But, in general, apes seem to lack the impulse toward collective problem— solving that’s so central to human society. “Chimps do a lot of incredibly smart things,” Michael Tomasello, who heads up the institute’s department of develop— mental and comparative psychology, told me. “But the main diiference we’ve seen is ‘putting our heads together.’ If you were at the zoo today, you would never have seen two chimps carry something heavy together. They don’t have this kind of I collaborative project.” Paabo usually works late, and most nights he has dinner at the insti— tute, where the cafeteria stays open until 7 PM. One evening, though, he offered to knock off early and show me around downtown Leipzig. We vis— ited the church where Each is buried, and ended up at Auerbachs Keller, the bar to which Mephistopheles brings Faust in the fifth scene of Goethe’s play. (The bar was supposedly Goethe’s fa— vorite hangout when he was a university student.) Paabo’s wife, Linda Vigilant, an American pri— matologist who also works at the insti— tute, joined us. Paabo and Vigilant first met in the nineteen—eighties, in Berke— ley, but they didn’t get together until both moved to Leipzig, in the late nine— ties. (Vigilant was then married to an— other geneticist, who works at the insti— tute, too.) Paabo and Vigilant have a THE NEW YORKER, AUGUST 15 fa 22, 20“ 7| six—year—old son, and Vigilant has two older sons from her previous marriage. I had been to the zoo, and I asked Paabo about a hypothetical experiment. Ifhe had the opportunity to subject Ne— anderthals to the sorts of tests I’d seen in Pongoland,.what would he do? Did he thinkhe’d be able to talk to them? He sat back in his chair and folded his arms across his chest. “One is so tempted to speculate,” he said. “So I try to resist it by refusing questions suchas ‘Do I think theywould have spoken?’ Because, honestly, I don’t know, and in some sense you can specu- late with just as much justification as I can. , By now, scores of Neanderthal sites have been excavated, from western Spain to central Russia and from Israel to Wales. They give lots of hints about what Neanderthals were like, at least for those inclined to speculate. Nean— derthals were extremely tough—this is attested to by the thickness of their bones—and probably capable of beating modern humans to a pulp. They were adept at making stone tools, though they seem to have spent tens of thousands of years making the same tools over and over, with only marginal variation. At least on some occasions, they buried their dead. Also on some occasions, they appear to have killed and eaten each‘ other. Wear on their incisors suggests that they spent a lot of time grasping an— imal skins with their teeth, which in turn suggests that they processed hides into some sort of leather. Neanderthal skele- tons very often show evidence of disease or disfigurement. The original Nean— derthal, from Mettmann, for example, seems to have suifered and recovered from two serious injuries, one to his head and the other to his left arm. The ‘ Neanderthal whose nearly complete skel— eton was found in La Chapelle endured, in addition to arthritis, a broken rib and kneecap. Both individuals survived into their fifties, which indicates that Nean— derthals had the capacity for collective action, or, if you prefer, empathy. They must—at least sometimes—have cared for their wounded. From the archeological record, it’s in— ferred that Neanderthals evolved in Europe or western Asia and spread out from there, stopping when they reached water or some other significant obstacle. 72 THE NEW YORKER, AUGUST l5 6: 22, 201] (During the ice ages, sea levels were a lot lower than they are now, so there was no English Channel to cross.) This is one of the most basic ways modern humans difirer from Neanderthals and, in Paabo’s view, also one of the most intriguing. By about forty—five thousand years ago, modern humans had already reached ‘ Australia, a journey that, even mid—ice age, meant crossing open water. Archaic humans like Homo erectus “spread like many other mammals in the Old World,” Paabo told me. “They never came to Madagascar, never to Australia. Neither did Neanderthals. It’s only fully modern humans who start this thing of venturing out on the ocean Where you don’t see land. Part of that is technology, of course; you have to have ships to do it. But there is also, I like to think or say, some madness there. You know? How many people must have sailed out and vanished on the Pacific before you found Easter Island? I mean, it’s ridiculous. And why do you do that? Is it for the glory? For immortality? For curiosity? And now we go to Mars. We never stop.” If the defining characteristic of modern humans is this 'sort of Faustian restlessness, then, by Paabo’s account, there must be some sort of Faustian gene. Several times, he told me that he thought it should be possible to identify the basis for this “madness” by compar— ing Neanderthal and human DNA. “If we one day will know that some freak mutation made the human insanity and exploration thing possible, it will be amazing to think that it was this little in- version on this chromosome that made all this happen and changed the whole eco— system of the planet and made us domi— nate everything,” he said at one point. At another, he said, “We are crazy in some way. What drives it? That I would really like to understand. That would be really, really cool to know.” ccording to the most recent esti- mates, Neanderthals and modern humans share a common ancestor who lived about four hundred thousand years ago. (It is unclear who that ancestor was, though one possibility is the somewhat shadowy hominid known, after a jaw- bone found near Heidelberg, as Homo beia’elbergemz's.) The common ancestor of chimps and humans, by contrast, lived some five million to seven million years ago. This means that Neanderthals and humans had less than one—tenth the lime to accumulate genetictdifferences. Mapping these differences is, in prin— Ciple7 pretty Straightforward—no harder; say, than comparing rival editions of “Hamlet.” In practiCe, it’s quite a bit more complicated. To begin with, there’s really no such thing as [be human genome; CV“ eryone has his or her gym genome, and theyvaiy substantiafly—bemeen you and the person sitting next to you on the sub- way, the diiferences are likely to amount to some three million base pairs. Some of these variations correspond to observable physiological difi‘erences—the color of your eyes, say, or your likelihood of devel- oping heart disease—and some have no known significance. To a first approxi- mation, ‘a human and a Neanderthal cho— sen at random would also vary by three million base pairs. The trick is ascertain— ing which of these millions of variations divide ustfrom them. Paabo estimates that when the Neanderthal Genome Project is completed, the list of base—pair changes that are at once unique to hu— mans and shared by all humans will number around a hundred thousand. Somewhere in this long list will lie the change—or changes—that made us human to begin with. Identifi/ing these key mutations is where the transgenic mice come in. I From an experimental viewpoint, the best way to test whether any particular change is significant would be to produce a human with the Neanderthal version of the sequence. This would involve manip— ulating a human stem cell, implanting the genetically modified embryo into a surro— gate mother, and then watching the re— sulting child grow up. For obvious rea— sons, such Island of Dr. Moreau-like research on humans is not permitted, nor is it necessarily even possible. For similar reasons, such experimentation isn’t al— lowed on chimpanzees. But it is allowed on mice. Dozens of strains of mice have been altered to carry humanized DNA sequences, and new ones are being cre— ated all the time, more or less to order. Several years ago, Paabo and a col- league, Wolfgang Enard, became inter— ested in a gene known as FOXPZ, which in humans is associated with language. (People who have a faulty copy of the gene—an extremely rare occurrence~ are capable of speech, but what they say _« a. m--- is, to strangers, mostly incomprehensi— ble.) Paabo and Enard had some mice bred with a humanized version of the gene, and then studied them from just about every possible angle. The altered mice, it turned out, squeaked at a lower pitch than their un—humanized peers. They also exhibited measurable differ. ences in neural development. (While I was in Leipzig, lwatched a graduate stu— dent cut the heads off some of the altered mice and then slice up their brains, like radishes.) The Neanderthals’ FOXPZ gene, it turns out, is in almost all ways identical to humans’, but there is one suggestive base—pair difi‘erence, When this difference was discovered, it prompted Paabo to order up a new round of trans— genic mice, which, at the time of my visit, had just been born and were being raised under sterile conditions in the basement. Genes that seem to play a role in speech are obvious places to look for human-specific changes. But one of the main points of sequencing the Neander— thal genome is that the most obvious places to look may not be the right ones. “The great advantage with genomics in this form is that it’s unbiased,” Paabo told me. “If you go after candidate genes, you’re inherently saying what you think the most important thing is. Language, many people would say. But perhaps we will be surprised—perhaps it’s some— thing else that was really crucial.” Re— cently, Paabo has become interested in a gene known as RUNXZ, which is in— volved in bone formation. When mem— bers of his team analyzed the human and Neanderthal genomes mathematically, RUNXZ emerged as a place where sig— . nificant changes in the human lineage seem to have occurred. People who have faulty copies of the RUNXZ gene often develop a condition, known as cleido— cranial dysplasia, whose symptoms in— clude such Neanderthal—like features as a flared rib cage. Two genes that have been implicated in autism, CADPSZ and AUTSZ, also appear to have changed substantially between Neanderthals and humans. This is interesting because one of the symptoms of autism is an inability to read social cues. ne afternoon, when I wandered into his office, Paabo showed me a pho— tograph of a skullcap that had recently been discovered by an amateur collector about half an hour from Leipzig. From the photograph, which, had been e-mailed to him, Paabo had decided that the Skullcap could be quite ancient—~from an early Ne— anderthal, or even a Homo laez'a’elbergemz's. He’d also decided that he had to have it. The skullcap had been found at a quarry in a pool of water—perhaps, he theorized, these conditions had preserved it, so that if he got to it soon, he’d be able to extract some DNA. But the skull had already been promised to a professor of anthropol— ogy in Mainz. How could he persuade the professor to give him enough bone to test? Paabo called everyone he knew who he thought might know the professor. He had his secretary contact the profes— sor’s secretaiy to get the professor’s private From: Com SYRANGER T0 , 1 M know gov. You AWOL know me. Goa” H4455 how 1+‘S meam’t TO HA PW mus/<3 F DA Y! gr;- We‘m \ooiL aiiVe «T Tina Same time, So lane's a card,“ Hm’i sud, a crime? 3935f L0 80TH€R _ You. a 3: Wm Maw l #3009 WWW mam Roscs oxre red, Sidewalks are army, WEN WflVfr Mei, Ami ihmils OK. FORGET THIS m 5355 #APPE/on. “Warsaw”: i" * cell—phone number, and joked—or maybe only half joked—that he’d be will— ing to sleep with the professor if that would help. The frenzy of phoning back and forth across Germany lasted for more than an hour and a half, until Paabo finally talked to one of the researchers in his own lab. The researcher had seen the actual skullcap and concluded that it probably wasn’t very old at all. Paabo im— mediately lost interest in it. With old bones, you never really know what you’re going to get. A few years ago, Paabo managed to get hold of a bit of tooth from one of the so—called “hobbit” skeletons found on the island of Flores, in Indonesia. (The “hobbits,” who were discovered in 2004, are gener— ally believed to have been diminutive archaic humans—Homofloresiensis— though some scientists have argued that they were just modern humans who suffered from microcephaly.) The tooth, which was about seventeen thousand years old, yielded no DNA. Then, about a year and a half ago, Paabo obtained a fragment of finger bone that had been unearthed in a cave in southern Siberia along with a weird, vaguely human—looking molar. The finger bone—about the size of a pencil eraser—~was believed to be more than forty thousand years old. Pa'abo assumed 74 THE NEW YORKER, AUGUST [5 é 22, 20” IV ...... jesus H-Chrisi— again as {1’1" +Ae SQACTQ(ST 5 hamafm m that it came either from a modern human or from a Neanderthal. Ifit proved to be the latter, then the site would be the far— thest east that Neanderthal remains had been found. In contrast to the hobbit tooth, the finger fragment yielded astonishingly large amounts of DNA. When the anal— ysis of the first bits was completed, Paabo happened to be in the United States. He called his oflice, and one of his colleagues said to him, “Are you sitting down?” The DNA showed that the digit could not have belonged to a Neanderthal or to a modern human. Instead, its owner must have been part of some entirely different and previously unsuspected type of hom— inid. In a paper published in December, 2010, in Nature, Paabo and his team dubbed this group the Denisovans, after the Denisova Cave, where the bone had been found. “GIVING ACCEPTED PREHIS~ TQRIC HISTORY THE FINGER,” ran the headline on the story in the Sydney Morning Herald Amazingly—~or per— haps, by now, predictably—modern hu— mans must have interbred with Deniso— vans, too, because contemporary New Guineans carry up to six per cent Deniso— van DNA. (Why this is true of New Guineans but not native Siberians or Asians is unclear, but presumably has to do with patterns of human migration.) It has been understood for a long time that modern humans and Neanderthals were contemporaries. The discovery of the hobbits and now the Denisovans shows that humans shared the planet with at least two additional creatures like our~ selves. And it seems likely that as DNA from more ancient remains is analyzed still other human relatives will be found; as Chris Stringer, a prominent British pa~ leoanthropologist, told me, “I’m sure we’ve got more surprises to cume.” “If these other forms of humans had survived two thousand generations more, which is not so much, then how would that have influenced our View of the liv— ing world?” Paabo said, once the excite— ment over the skullcap had passed and we were sitting over coffee. “We now make this very clear distinction between hu— mans and animals. But it might not be as clear. That is sort of an interesting thing to philosophize about.” It’s also interest— ing to think about why we’re the ones who survived. Over the decades, many theories have been offered to explain what caused the demise of the Neanderthals, ranging from climate change to simple bad luck. In recent years, though, it’s become in— creasingly clear that, as Paabo put it to me, "their bad luck was us.” Again and again, the archeological evidence in Eu— rope indicates, once modern humans showed up in a region where Neander— thals were living, the Neanderthals in that region vanished. Perhaps the Neander— thals were actively pursued, or perhaps they were just outcompeted. The Nean— derthals’ "bad luck” is presumably the same misfortune that the hobbits and the Denisovans encountered, and similar to the tragedy suifered by the giant marsu— pials that once browsed Australia, and the varied megafauna that used to inhabit North America, and the moas that lived in New Zealand. And it is precisely the same bad luck that has brought so many species—including every one of the great apes——to the edge of oblivion today. “To me, the mystery is not the extinc— tion of the Neanderthals,” Jean—Jacques Hublin, the director of the Institute for Evolutionary Anthropology’ s department of human evolution, told me. “To me the mystery is what makes modern humans such a successful group that they have been replacing not just the Neanderthals but evmyt/ying. We don’t have much evi~ dence that the Neanderthals or other ar— chaic humans ever led to an extinction of a species of mammal or anything else. For modern humans, there are hundreds of examples, and we do it very well.” ne of the largest assemblages of Neanderthal bones ever found— . remains from seven individuals—was dis— covered about a century ago at a spot known as La Ferrassie, in southwestern France. La Ferrassie is in the Dordogne, not far from La Chapelle and within half an hour’s drive of dozens of other impor— tant archeological sites, including the painted caves at LasCaux. Over the surn- mer, a team that included one of Paabo’s colleagues was excavating at La Ferrassie, and I decided to go down and have a look. I arrived at the dig’s headquarters—— a converted tobacco barn—just in time for a dinner of boeuf bourguignonne, which was served on makeshift tables in the back yard. The next day, I drove out to La Fer— rassie with some of the team’s archeolo— gists. The site lies in a sleepy rural area, right by the side of the road. Many thou— sands of years ago,.La Ferrassie was a huge limestone cave, but one of the walls has since fallen in, and now it is open on two sides. A massive ledge of rock juts out about twenty feet off the ground, like half of a vaulted ceiling. The site is ringed by a wire fence and hung with tarps, which give it the aspect of a crime scene. The day was hot and dusty. Half a dozen students crouched in a long trench, picking at the dirt with trowels. Along the side of the trench, I could see bits of bone sticking out from the reddish soil. The bones toward the bottom, I was told, had been tossed there by Neanderthals. The bones near the top were the leavings of modern humans, who occupied La Ferrassie once the Neanderthals were gone. The Neanderthal skeletons from the site had long since been removed, but there was still hope that some stray bit, like a tooth, might be found. Each bone fragment that was unearthed, along with every flake of flint and anything else that might even remotely be of interest, was set aside to be taken back to the head— quarters to be sorted and tagged. After watching the students chip away for awhile, I retreated to the shade. I tried to imagine what life had been like for the Neanderthals at La Ferrassie. Though the area is now wooded, then it would have been tundra. There would have been elk roaming the valley, and reindeer and wild cattle and mammoths. Beyond these stray facts, not much came to me. I put the question to the archeologists I had driven out with. “Itwas cold,” Shannon McPherron, of the Max Planck Institute, volunteered. “And smelly,” Dennis Sandgathe, of Canada’s Simon Fraser University, said. “Probably hungry,” Harold Dibble, of the University of Pennsylvania, added. “No one would have been very old,” Sandgathe said. Later on, back at the barn, I picked through the bits and pieces that had been dug up over the past few days. There were hundreds of fragments of animal bone, each ofwhich had been cleaned and num— bered and placed in its own little plastic bag, and hundreds of flakes of flint. Most of the flakes were probably the detritus of toolrnaking—the Stone Age equivalent of wood shavings—but some, I learned, were the tools themselves. Once I was shown what to look for, I could see the bevelled edges that the Neanderthals had crafted. One tool in particular stood out: a palm—size flint shaped like a teardrop. In archeological terms, it was a hand axe, though it probably was not used as an axe in the contemporary sense of the word. It had been found near the bottom of the trench, so it was estimated to be about seventy thousand years old. I took it out of its plastic bag and turned it over. It was al— most perfectly symmetrical and—to a human eye, at least—quite beautiful. I said that I thought the Neanderthal who had fashioned it must have had a keen sense of design. McPherron objected. “We know the end of the story,” he told me. “We know what modern culture looks like, and so then what we do is we want to explain how we got here. And there’s a tendency to overinterpret the past by projecting the present onto it. So when you see a beautiful hand axe and you say, ‘Look at the craftsmanship on this; it’s virtually an object of art,’ that’s THE NEW YORKER, AUGUST I5 <2 22, 20“ your perspective today. But you can’t as— sume what you’re trying to prove.” Among the hundreds of thousands of Neanderthal artifacts that have been un—I earthed, almost none represent unambig— uous attempts at art or adornment, and those which have been interpreted this way—for instance, ivory pendants dis— covered in a cave in central France——are the subject of endless, often abstruse dis- putes. (Many archeon/ogists believe that the pendants were created by Neander— thals who had come into contact with modern humans and were trying to imi— tate them, but, relying on the most recent dating techniques, some argue that the pendants were, in fact, created by modern humans.) This paucity has led some to propose that Neanderthals were not ca— pable of art or—what amounts to much the same thing—not interested in it. They simply did not possess what, ge— nomically speaking, might be called the aesthetic mutation. On my last dayin the Dordogne, I de— cided to visit a nearby human site known for its extraordinary images. The site, Grotte des Combarelles, is a long, very narrow cave that zigzags through a lime— stone cliff. Hundreds of feet in, the walls of the cave are-covered with engravings—— a mammoth curling its trunk, a wild. horse lifting its head, a reindeer leaning forward, apparently to drink. In very re— cent times, the floor of the Grotte des Combarelles has been dug out, so that a person can walk in it, and the tunnel is dimly lit by electric lights. But when the etchings were originally created, some twelve or thirteen thousandyears ago, the only way to gain access to the site would have been to crawl, and the only way to see in the absolute dark would have been to carry fire. As I crept along through the gloom, past engravings of wisent and au— rochs and woolly rhinos, it occurred to me that I really had no clue what would drive someone to wriggle through a pitch—black tunnel to cover the walls with images that only another, similarly driven soul would see. Yet it also struck me that so much of what is distinctively human was here on display—creativity, daring, “madness.” And then there were the ani— mals pictured on the walls—ethe aurochs and mammoths and rhinos. These were the beasts that Paleolithic Europeans had hunted, and then, one by one, as with the Neanderthals, obliterated. O 75 ...
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Sleeping w the Enemy-1 - ANNALS OF EVOLUTION SLEEPING WTH...

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