The Max Planck Institute for Evolutionary 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 neighborhood 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 Pääbo heads the institute’s department 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. Pääbo’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 likeness of Pääbo, but in mismatched colors that make it look as if he had a skin disease.
At any given moment, Pääbo has at least half a dozen research efforts in progress. 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 team was slicing open the brains of mice that had been genetically engineered to produce a human protein.
In Pääbo’s mind, at least, these research efforts all hang together. They are attempts to solve a single problem in evolutionary genetics, which might, rather dizzyingly, be posed as: What made us the sort of animal that could create a transgenic mouse?
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 resolved, then this, Pääbo suspects, is because it has never been properly framed. “The challenge is to address the questions that are answerable,” he told me.
Pääbo’s most ambitious project to date, which he has assembled an international consortium to assist him with, is an attempt to sequence the entire genome of the Neanderthal. The project is about halfway complete and has already yielded some unsettling results, including the news, announced by Pääbo last year, that modern humans, before doing in the Neanderthals, must have interbred with them.
Once the Neanderthal genome is complete, 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, Pääbo 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. Pääbo 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 Neanderthals, that made a difference,” he said. “What made it possible for us to build up these enormous societies, and spread around the globe, and develop the technology that I think no one can doubt is unique to humans. There has to be a genetic basis for that, and it is hiding somewhere in these lists.”
Pääbo, 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 Bergström, who later won a Nobel Prize. Pääbo 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. Bergström had a wife and another son; Pääbo’s mother, meanwhile, never married. Every Saturday, Bergström would visit Pääbo and take him for a walk in the woods, or somewhere else where he didn’t think he’d be recognized.
“Officially, at home, he worked on Saturday,” Pääbo 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, Pääbo wasn’t particularly bothered by the whole arrangement; later, he occasionally threatened to knock on Bergström’s door. “I would say, ‘You have to tell your son—your other son—because he will find out sometime,’ ” he recalled. Bergström would promise to do this, but never followed through. (As a result, Bergström’s other son did not learn that Pääbo existed until shortly before Bergström’s death, in 2004.)
From an early age, Pääbo was interested in old things. He discovered that around fallen trees it was sometimes possible to find bits of pottery made by prehistoric 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 enrolled at Uppsala University, planning to become an Egyptologist.
“I really wanted to discover mummies, like Indiana Jones,” he said. Mostly, though, the coursework turned out to involve parsing hieroglyphics, and instead of finding it swashbuckling Pääbo thought it was boring. Inspired by his father, he switched first to medicine, then to cell biology.
In the early nineteen-eighties, Pääbo 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), Pääbo conducted his mummy research in secret, at night. With the help of one of his former 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 obscure 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 Pääbo thought mummy DNA could answer were what caused pharaonic dynasties to change and who Tutankhamun’s mom was.
While Pääbo was preparing a version of his mummy paper for publication in English, a group of scientists from the University of California at Berkeley announced that they had succeeded in sequencing a snippet of DNA from a zebralike 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 biochemist who had, among other things, come up with a way to study evolution using the concept of a “molecular clock.” Pääbo sent Wilson the galleys of his mummy paper. Impressed, Wilson replied asking if there was any space in Pääbo’s lab; he might like to spend a sabbatical there. Pääbo 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.
Pääbo’s mummy paper became the cover article in Nature. It was also written up in the Times, which called his achievement “the most dramatic of a series of recent accomplishments using molecular biology.” Pääbo’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, Pääbo 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, Pääbo 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 technology that’s necessary to test the hypotheses. And to have all three of those capacities is really remarkable.” Also, although “they were 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 together in the shape of a ladder—the famous double helix. Each nucleotide contains one of four bases: adenine, thymine, guanine, and cytosine, which are designated by the letters A, T, G, and C, so that a stretch of the human genome might be represented as ACCTCCTCTAATGTCA. (This is an actual sequence, from chromosome 10; the comparable 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 junk.
“Your mother and I are separating because I want what’s best for the country and your mother doesn’t.” Link copied
With the exception of red blood cells, every cell in an organism contains a complete copy of its DNA. It also contains many copies—hundreds to thousands—of an abridged form of DNA known as mitochondrial 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, disintegrate. “Maybe in the permafrost you could go back five hundred thousand years,” Pääbo told me. “But it’s certainly on this side of a million.” Five hundred thousand 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 humans did not yet exist.
When Pääbo 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 single 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 contamination was a huge problem,” he explained. (Eventually, Pääbo concluded that the sequences he had obtained for his original mummy paper had probably been corrupted in this way.) As a sort of warmup exercise, he began working on extinct animals. 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 Australia than to kiwis, the flightless birds that inhabit New Zealand today. “That was a blow to New Zealand self-esteem,” he recalled. He also probed plenty of remains that yielded no usable DNA, including bones from the La Brea tar pits and fossilized insects preserved in amber. In the process of this work, Pääbo more or less invented the field of paleogenetics.
