Sleeping with the Enemy

The geneticist Svante P??bo was awarded the Nobel Prize in Physiology or Medicine today. Revisit ElizKolbert on P??bo’s most ambitious project: sequencing the entire genome of the Neanderthal.

What happened between the Neanderthals and us?

Homo erectusAccording to the most recent estimates, 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 jawbone found near Heidelberg, as

Mapping these differences is, in principle, 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 asFrom 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 manipulating a human stem cell, implanting the genetically modified embryo into a surrogate mother, and then watching the resulting child grow up. For obvious reasons, 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 allowed 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 created all the time, more or less to order.

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Shopping By now, scores of Neanderthal sites have been excavated, from western Spain to central Russia and from Israel to Wales.profile depicted in popular culture is not untrue, but it is by no means the only depressive experience.Gigi Hadid commented, while Kim questioned if she was rocking one of her new SKIMS bras.11:26PM ET Nick Brundle Photography via Getty Immediately after exiting the central railway station in Aarhus, visitors are greeted by a bustling pedestrian-only street with quaint red-brick facades, a towering Gothic revival church, mountains of bicycles parked in an organized chaos–all of it very Danish.

They give lots of hints about what Neanderthals were like, at least for those inclined to speculate. Neanderthals were extremely tough–this is attested to by the thickness of their bones–and probably capable of beating modern humans to a pulp. While the Diagnostic and Statistical Manual (DSM) has for decades provided descriptions of various depressive disorders and their subtypes, it still fails to address a key fact that experienced clinicians recognize and that has been put forth by numerous researchers over the years (e. 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. She paired the bold look with a floral bustier mini dress and matching pumps, and kept her long, dark hair straight and swept to the side. At least on some occasions, they buried their dead., Rosenfeld, 1959; Dutton & Karakonta, 2013; Meyrueix et al. Also on some occasions, they appear to have killed and eaten each other. But what I discovered over several days is that it’s much more than that.

Wear on their incisors suggests that they spent a lot of time grasping animal skins with their teeth, which in turn suggests that they processed hides into some sort of leather. So prevalent this is, that, in 2001, the researcher van Praag suggested a new depression diagnostic consideration based on unique biomarkers behind many people who tend to be aggressive while depressed. Neanderthal skeletons very often show evidence of disease or disfigurement. The original Neanderthal, from Mettmann, for example, seems to have suffered and recovered from two serious injuries, one to his head and the other to his left arm.. The Neanderthal whose nearly complete skeleton was found in La Chapelle endured, in addition to arthritis, a broken rib and kneecap. Both individuals survived into their fifties, which indicates that Neanderthals had the capacity for collective action, or, if you prefer, empathy. persistent anger, a tendency to respond to events with angry outbursts or blaming others, or an exaggerated sense of frustration over minor matters,” is not uncommon.” The city’s reflects, in its own words, “a deep political belief that art, culture and community are essential for a flourishing city.

They must–at least sometimes–have cared for their wounded. From the archeological record, it’s inferred that Neanderthals evolved in Europe or western Asia and spread out from there, stopping when they reached water or some other significant obstacle. Consider, however, what happens when this child”ages out” of DMDDoC, and angry, depressed adults exhibit aggressive acts? It’s been my experience that this can lead clinicians to immediately wonder about personality disorders or jump to considering an intermittent explosive disorder diagnosis. (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 differ from Neanderthals and, in Pääbo’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. And they actually mean it.

Archaic humans like Homo erectus “spread like many other mammals in the Old World,” Pääbo 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. Andrew Kirell for The Daily Beast The six-course menu changes weekly or even daily–all depending on what materials they’ve got in stock.

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 Pääbo’s account, there must be some sort of Faustian gene. Elsewhere in town, there’s no shortage of top-notch meals.

Several times, he told me that he thought it should be possible to identify the basis for this “madness” by comparing 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 inversion on this chromosome that made all this happen and changed the whole ecosystem of the planet and made us dominate 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.

” According to the most recent estimates, 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 jawbone found near Heidelberg, as Homo heidelbergensis .) 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 time to accumulate genetic differences. Mapping these differences is, in principle, 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 the human genome; everyone has his or her own genome, and they vary substantially–between you and the person sitting next to you on the subway, the differences are likely to amount to some three million base pairs. Some of these variations correspond to observable physiological differences–the color of your eyes, say, or your likelihood of developing heart disease–and some have no known significance. To a first approximation, a human and a Neanderthal chosen at random would also vary by three million base pairs. The trick is ascertaining which of these millions of variations divide us from them.

Pääbo estimates that when the Neanderthal Genome Project is completed, the list of base-pair changes that are at once unique to humans 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. Identifying these key mutations is where the transgenic mice come in. 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 manipulating a human stem cell, implanting the genetically modified embryo into a surrogate mother, and then watching the resulting child grow up.

For obvious reasons, 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 allowed 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 created all the time, more or less to order.

Several years ago, Pääbo and a colleague, Wolfgang Enard, became interested in a gene known as FOXP2, 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 is, to strangers, mostly incomprehensible.) Pääbo 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 differences in neural development.

(While I was in Leipzig, I watched a graduate student cut the heads off some of the altered mice and then slice up their brains, like radishes.) The Neanderthals’ FOXP2 gene, it turns out, is in almost all ways identical to humans’, but there is one suggestive base-pair difference. When this difference was discovered, it prompted Pääbo to order up a new round of transgenic 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 Neanderthal 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,” Pääbo 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 something else that was really crucial.” Recently, Pääbo has become interested in a gene known as RUNX2, which is involved in bone formation.

When members of his team analyzed the human and Neanderthal genomes mathematically, RUNX2 emerged as a place where significant changes in the human lineage seem to have occurred. People who have faulty copies of the RUNX2 gene often develop a condition, known as cleidocranial dysplasia, whose symptoms include such Neanderthal-like features as a flared rib cage. Two genes that have been implicated in autism, CADPS2 and AUTS2, 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. One afternoon, when I wandered into his office, Pääbo showed me a photograph 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, Pääbo had decided that the skullcap could be quite ancient–from an early Neanderthal, or even a Homo heidelbergensis . 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 anthropology in Mainz. How could he persuade the professor to give him enough bone to test? Pääbo called everyone he knew who he thought might know the professor.

He had his secretary contact the professor’s secretary to get the professor’s private cell-phone number, and joked–or maybe only half joked–that he’d be willing 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 Pääbo 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. Pääbo immediately lost interest in it. With old bones, you never really know what you’re going to get.

A few years ago, Pääbo 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 generally believed to have been diminutive archaic humans– Homo floresiensis –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, Pääbo 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.

Pääbo assumed that it came either from a modern human or from a Neanderthal. If it proved to be the latter, then the site would be the farthest east that Neanderthal remains had been found. In contrast to the hobbit tooth, the finger fragment yielded astonishingly large amounts of DNA. When the analysis of the first bits was completed, Pääbo happened to be in the United States. He called his office, 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 hominid. In a paper published in December, 2010, in Nature , Pääbo and his team dubbed this group the Denisovans, after the Denisova Cave, where the bone had been found. ” GIVING ACCEPTED PREHISTORIC HISTORY THE FINGER ,” ran the headline on the story in the Sydney Morning Herald. Amazingly–or perhaps, by now, predictably–modern humans must have interbred with Denisovans, too, because contemporary New Guineans carry up to six per cent Denisovan 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.

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