• Science & Nature

Neanderthal Man

Svante Paabo has probed the DNA of Egyptian mummies and extinct animals. Now he hopes to learn more about what makes us tick by decoding the DNA of our evolutionary cousins.

• By Steve Olson
• Smithsonian magazine, October 2006

As a boy in Sweden, Svante Paabo read everything he could about ancient civilizations. After powerful North Sea storms uprooted trees, he begged his parents to take him to archaeological sites to look for potsherds and other artifacts. When he was 13, his mother, a food chemist in Stockholm, yielded to her son's most frequent request: to visit Egypt. "It was absolutely fascinating," he recalls. "We went to the pyramids, to Karnak and the Valley of the Kings. The soil was full of artifacts."

Paabo, 51, is still looking for artifacts, but in a very different place. He's a leader of the worldwide quest to explore the past by analyzing human DNA. He has helped show that human groups—southern Africans, Western Europeans, Native Americans—are closely related, despite superficial distinctions. He has been uncovering key genetic changes that helped transform our shambling, hirsute ancestors into the brainy bipeds we are today. This past summer, Paabo announced that he and his co-workers were going to take the next—and biggest—step, in their effort to resurrect the genome of the Neanderthal, our distant evolutionary cousin, who went extinct 30,000 years ago. The first scientist to analyze segments of DNA from Neanderthal bones, Paabo now wants to re-create the entire DNA sequence of a Neanderthal and compare it with our own, looking for the reasons that one evolutionary experiment failed and the other succeeded. "He really is a visionary," says Mary-Claire King, a geneticist at the University of Washington.

Paabo is director of the genetics department at the gleaming new Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. But you'd never guess his heady position from his taste in clothes, which leans toward shorts and Hawaiian shirts. In his simply decorated office, he kicks off his clogs, folds his long legs under his angular body to perch on a sofa, and grins. "It is a wonderful time to be working in this field," he says.

Ever since the 1940s, when DNA was identified as the molecule that carries genetic information between generations, scientists have predicted that the study of genetics would yield great things, from drought-resistant crops to cures for genetic diseases. Recently, geneticists have realized that there is another way of looking at DNA—as a link to history. All of us inherited our DNA from our biological parents, who inherited it from their biological parents, and so on. Like an ancient manuscript that is copied and recopied with each generation, DNA bears tales from beyond memory. It also carries a unique time stamp: DNA is copied imperfectly, and these minor changes are passed from one generation to the next. Scientists can date these changes by comparing DNA among humans or between humans and other species. In this way, DNA connects us not only with our ancestors but also with the animals from which we evolved.

Paabo enrolled at the University of Uppsala, in 1975, to study Egyptology. But rather than excavate exotic archaeological sites, as he expected, he spent most of his time conjugating ancient Egyptian verbs. "It was not at all what I wanted to do." Soon he found himself in medical school, a route his biochemist father had also taken. Then he entered a PhD program in molecular immunology. Still, he couldn't shake his fascination with Egypt. "I knew about these thousands of mummies that were around in museums," he recalls, "so I started to experiment with extracting DNA.” With the help of his old Egyptology professors, Paabo obtained skin and bone samples from 23 mummies. Working nights and weekends (Paabo was worried that his immunology professor would not approve of the project), he succeeded in extracting and analyzing a short segment of DNA from the 2,400-year-old mummy of an infant boy. In early 1985, he sent his results to Nature, one of the world's leading scientific journals, which made the paper its cover story—the equivalent in science of hitting a grand slam in your first professional at-bat.

Paabo also sent a copy of the manuscript to Allan Wilson, a molecular biologist at the University of California at Berkeley. Wilson had made headlines when he and his colleagues extracted a fragment of DNA from the remains of a quagga, a zebra-like creature that went extinct in 1883. After Wilson read Paabo's paper, he asked if he could go to Paabo's lab for a sabbatical. "I hadn't even finished my PhD!" Paabo says. Paabo wrote back with a counteroffer: Could he work in Wilson's lab?

Wilson, who died of leukemia in 1991 at the age of 56, "was one of the best people I’ve ever seen at generating ideas," says Mark Stoneking, who worked with Wilson in the 1980s and is now one of Paabo's colleagues at the institute. Stoneking helped Wilson establish the existence of "mitochondrial Eve"—a woman who lived in Africa about 200,000 years ago. The Berkeley scientists traced our ancestry to her by analyzing the DNA in mitochondria, parts of a cell that produce energy and operate somewhat independently of the rest of the cell. We inherit mitochondria through our mothers, grandmothers, great-grandmothers, and so on. By analyzing the mitochondrial DNA of people throughout the world, Wilson and his colleagues determined that the maternal lineages of everyone alive today converge on a single ancient woman.

Paabo, meanwhile, was developing new ways of extracting DNA from preserved specimens of extinct organisms, including moas (a giant flightless bird) and marsupial wolves. Others in Wilson's lab were trying to find DNA in fossilized plants and animals. In the acknowledgments of his 1990 novel Jurassic Park, author Michael Crichton gives part of the credit for his inspiration to Berkeley's Extinct DNA Study Group.

Paabo landed his first academic post at the University of Munich in 1990. There he expanded his work on the DNA of ancient animals and plants—mammoths, maize, European cave bears. He also resumed his work on ancient human DNA; for example, he was part of the team that managed to sequence some DNA from the “Ice Man,” who was frozen into a glacier in the Tyrolean Alps more than five millennia ago and discovered in 1991. That success fired Paabo's ambition to take on one of the toughest questions in paleoanthropology: What is the nature of our kinship with extinct hominids?

In 1856, two quarrymen dug up a set of odd-looking human bones in the Neander Valley, near Düsseldorf, Germany. The remains were the first recognized traces of a group that came to be known as the Neanderthals (thal means "valley" in German). For the past 150 years, scientists have argued about the relationship between today's humans and these vanished people. When anatomically modern humans—the ancestors of today's Europeans—began migrating into Europe about 40,000 years ago, did the Neanderthals simply die out? Or did they interbreed with the newcomers, contributing some DNA to the gene pool of today's humans?

Paabo decided to look for DNA in the original Neanderthal bones. Needless to say, the curators at the Rhineland Museum in Bonn, who are responsible for the fossilized bones, were not eager to let him take samples. Analyzing the bones would mean grinding up irreplaceable fossil material and dissolving it in chemicals. But Paabo persisted, and the curators finally agreed. A bone specialist sawed a half-inch chunk from the upper right arm bone of a 42,000-year-old Neanderthal fossil.

Paabo handed over the sample to graduate student Matthias Krings, who wasn't optimistic—extracting DNA from 3,000-year-old mummies had been hard enough. He focused on DNA from the mitochondria, which is much shorter and more plentiful than the DNA that dictates the workings of the rest of the body. Soon Krings began to find DNA sequences that were clearly different from those of any human beings living today.

The results, along with those of subsequent studies, indicated that Neanderthals contributed little, if any, DNA to modern humans. Instead, they appear to have been displaced by modern humans—the taller, more graceful creatures with round skulls and prominent chins who first appear in the fossil record in eastern Africa about 200,000 years ago. The Neanderthals retreated into more remote parts of Europe before going extinct. Paabo's work means that during the thousands of years that Neanderthals shared the continent with modern humans, there was probably little interbreeding between the two groups. The same thing happened in other parts of the world: archaic populations of humans in Africa and Asia gradually went extinct without leaving an obvious genetic trace.

The apparent lack of interbreeding between archaic and modern humans means that we are a very young species—brash upstarts that overran the older and more established species of humans. "In a sense, we are all Africans, though some of us have gone to live in exile," Paabo says. To be sure, physical appearances changed as groups of modern humans moved into different environments. For example, as they moved into northern climates, natural selection appears to have favored lighter skin colors—probably because lighter skin admits more sunlight and thereby allows the body to synthesize sufficient vitamin D to endure long, dark winters. As a result, over many generations, the occupants of northern Europe and Asia gradually developed lighter skin than their ancestors. But these superficial differences disguise a remarkable genetic similarity. "Different subgroups of chimpanzees, such as those in eastern or western Africa," says Paabo, "have a much longer history of genetic separation than do, say, Chinese and Africans."

The German government provided very little support for anthropological research after World War II, a response to abhorrent wartime activities of the Kaiser Wilhelm Institute for Anthropology, Human Genetics and Eugenics in Berlin. (The head of the institute supported Nazi racial policies, and his assistant, Josef Mengele, sent body parts from Auschwitz to be studied at the institute.) But following the 1990 reunification of Germany, officials began looking for neglected areas of science to support in the effort to build new ties between East and West. In 1997, the government invited Paabo to move to Leipzig, a university town in the former East Germany, to start a new institute on human evolution with three other prominent scientists: Christophe Boesch of the University of Basel in Switzerland, who studies wild chimpanzees; Bernard Comrie, a linguist from the University of Southern California in Los Angeles; and psychologist Michael Tomasello from the Yerkes Primate Center in Atlanta. In the summer of 1997, the four scientists set off for a hike in the Alps south of Munich to mull over the invitation. By the time they returned from the mountains, they had decided to accept it. "There’s no reason to let Hitler keep us from working on human origins anymore," says Paabo.

Originally housed in an old Leipzig publishing house, the Institute for Evolutionary Anthropology moved in 2002 into a new $30 million building south of downtown. The four directors collaborated on the design, with Paabo insisting that a four-story rock-climbing wall be installed in the lobby. The directors agreed to focus their efforts on one particular question: What makes human beings unique? And to avoid empty speculation, they decided to work only on questions for which data are available. "The kinds of questions we ask are ones where we can see how to go about finding answers," says Comrie.

One day, Tomasello and Paabo were talking in the institute's cafeteria about a family in England with a remarkable genetic defect. Some members of the family have a mutation in a gene known as FOXP2, which helps direct the development of the brain during infancy and childhood. Every family member with the mutation had great difficulty speaking. Paabo had been thinking about how to identify genes that had changed during human evolution to make speech possible, and FOXP2 seemed like a prime candidate. He and his co-workers sequenced the gene—that is, they figured out the order of the DNA bases that make up FOXP2—in six different species. They found that it was one of the most stable genes they had ever studied; from mice to rhesus macaques to chimps, the protein produced by the gene is almost exactly identical, suggesting that the gene itself plays a fundamental role in animal function. But in humans the gene had undergone a slight modification. About 250,000 years ago, according to the scientists' calculations, two of the molecular units in the 715-unit DNA sequence of the gene abruptly changed. That's not long before modern humans first appeared in the fossil record. Could the changes in FOXP2 have enabled modern humans to speak? And could articulate speech have given modern humans an edge over the Neanderthals and other archaic humans?

That's certainly what some newspaper stories implied, labeling FOXP2 a "language gene." But Paabo and other scientists are more cautious. FOXP2 "is one of who knows how many genes that affect language ability," says Ken Weiss, an expert on evolution and genetics at Pennsylvania State University. The change in FOXP2 might have been entirely coincidental. Or the gene may be related to language indirectly—for example, by influencing coordination. And some scientists argue that language evolved much earlier than our version of FOXP2, and that archaic humans also had speech.

Still, Paabo's work on FOXP2 has raised fruitful questions. Researchers are genetically engineering mice with "broken" FOXP2 genes, to see how disruptions in the gene might affect the animals. Also, researchers are splicing the human version of the gene into mice to see if it makes any difference. (So far, none of the mice have started talking.)

More recently, Paabo has taken an even broader view of the genetic changes responsible for our uniquely human traits. For example, mutations in individual genes like FOXP2 may not be the most important force in evolution. An even bigger factor may be changes in the genetic switches that turn on and off many genes at once. Paabo and his colleagues have been looking at the patterns of gene activity in humans, chimps and other species. As might be expected, the brain has been a particularly active site for recent human evolution. Paabo's team finds that genes in the human brain have undergone more changes in how they are turned on than similar genes in chimp brains.

Paabo is also returning to one of his original obsessions. Using a fossil from a site in Croatia, he and his colleagues are trying to derive much longer Neanderthal DNA sequences—not just the DNA that runs the mitochondria, but the DNA that is responsible for building the rest of the body. Their goal is to reconstruct the entire genetic blueprint for making a Neanderthal. It's a technically daunting task, and Paabo estimates it will take about two years to finish. But being able to compare our genome with that of our evolutionary relatives could highlight key turning points in our evolution.

The ultimate goal of his research, Paabo says, is to identify the genetic changes that made us human. Of course, no historical event can ever be reconstructed completely. But by studying our DNA, scientists eventually will be able to say which genes changed, when they changed, and maybe even why they changed. At that point, we'll have something we've never had before: a scientifically plausible and relatively complete story of our biological origins.

About a mile north of the institute, down a dim alley and a flight of stairs, is a very old restaurant known as Auerbach's Cellar. In Johann Wolfgang von Goethe's 1808 epic play "Faust," the devil and Faust go drinking at Auerbach's. Shortly thereafter, Faust meets and talks with two apes—symbols, for Goethe, of human sinfulness and folly.

Faust, of course, sold his soul to the devil for knowledge. Will the knowledge generated by studying our DNA place limits on the human soul? Will people come to see themselves as biological automatons bereft of compassion and morality? Will genetics "biologize" human relationships, so that we begin to define ourselves and others in terms of our DNA sequences?

Paabo worries about such possibilities. DNA studies have revealed how similar we are to other organisms, even such lowly creatures as worms and flies. These discoveries have emphasized the unity of life, Paabo says, but they also have been "a source of humility and a blow to the idea of human uniqueness." Paabo, like most scientists, is an optimist. He believes that genetic knowledge will strengthen our commitments to each other, not rob us of purpose. And studying how we evolved may reveal why human beings suffer from diseases not found in other animals. He is particularly insistent that studies of the evolutionary origins of speech will help children who have congenital speech problems.

But Paabo also says that the possible benefits of research are not his principal motivation. "I'm driven by curiosity," he says, "by asking the questions, where do we come from, and what were the important events in our history that made us who we are. I'm driven by exactly the same thing that makes an archaeologist go to Africa to look for the bones of our ancestors."

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