The New York Times, March 20, 2018
BOSTON — David Reich wore a hooded, white suit, cream-colored clogs, and a blue surgical mask. Only his eyes were visible as he inspected the bone fragments on the counter.
Dr. Reich, a geneticist at Harvard Medical School, pointed out a strawberry-sized chunk: “This is from a 4,000-year-old site in Central Asia — from Uzbekistan, I think.”
He moved down the row. “This is a 2,500-year-old sample from a site in Britain. This is Bronze Age Russian, and these are Arabian samples. These people would have never met each other in time or space.”
Dr. Reich hopes that his team of scientists and technicians can find DNA in these bones. Odds are good that they will.
In less than three years, Dr. Reich’s laboratory has published DNA from the genomes of 938 ancient humans — more than all other research teams working in this field combined. The work in his lab has reshaped our understanding of human prehistory.
“They often answer age-old questions and sometimes provide astonishing unanticipated insights,” said Svante Paabo, the director of the Max Planck Institute of Paleoanthropology in Leipzig, Germany.
Dr. Reich, Dr. Paabo and other experts in ancient DNA are putting together a new history of humanity, one that runs in parallel with the narratives gleaned from fossils and written records. In Dr. Reich’s research, he and his colleagues have shed light on the peopling of the planet and the spread of agriculture, among other momentous events.
In a book to be published next week, “Who We Are and How We Got Here,” Dr. Reich, 43, explains how advances in DNA sequencing and analysis have helped this new field take off.
“It’s really like the invention of a new scientific instrument, like a microscope or a telescope,” he said. “When an instrument that powerful is invented, it opens up all these horizons, and everything is new and surprising.”
Dr. Reich oversees a team with many different skills, from genetics to mathematics. But the “clean lab” is where the raw material for all their work — ancient DNA — is recovered. The head-to-toe suits that the researchers don in an airlock each morning ensure that no stray flake of skin or bead of sweat contaminates the bones with modern DNA. Each night the entire lab is bathed in gene-destroying ultraviolet light.
The clean lab feels like it belongs in a computer chip factory. But Dr. Reich has not forgotten that these are human remains, not widgets on a conveyor belt.
“This is a bone from a person’s body who lived four thousand years ago, and we’re destroying it,” he said, gazing down at the Uzbek remains. “I think we need to do well by the individuals we’re studying.”
Doing well means understanding who these people were, and how they were linked to one another — and to us.
Standing next to Dr. Reich was a suited technician, Ann Marie Lawson. She picked up the Uzbek bone and lowered it into a box, which she covered with a clear plastic lid. She pushed her gloved hands through two rubber-lined holes on its sides.
She picked up the bone in her left hand; with her right hand, she switched on a sandblasting hose and pointed it at the bone. An outer layer of dirt flew upward, quickly sucked away by a fan in the box.
Ms. Lawson then inspected the freshly white bone. It came from the base of a skull, and deep inside was the inner ear. The bone that surrounds the inner ear turns out to be the best place in the body to search for ancient DNA.
Ms. Lawson began sandblasting again, chiseling away chunks of bone. Eventually, she was left holding a remnant only as big as a grain of rice.
“That’s the motherlode,” said Dr. Reich.
An Extraordinary Invitation
Dr. Reich grew up in Washington, the son of the novelist Tova Reich and Walter Reich, the first director of the Holocaust Memorial Museum and now a professor at George Washington University.
Dr. Reich began studying sociology as a Harvard undergraduate, but later he turned to physics and then to medicine. After graduating, he went to Oxford to prepare for medical school.
There he met Dr. David B. Goldstein, who at the time was comparing the DNA of living people for clues to what their distant ancestors were like.
“When I first met him, he was obviously smart, but he gave an impression of being a little bit shy and not having a very forceful personality,” said Dr. Goldstein.
“It turned out that’s the most misleading impression he could possibly give. He knows exactly what he wants to do.”
It was obvious that his student was captivated by the research. But Dr. Goldstein had come to view it as a scientific dead end.
“I said, ‘My God, don’t spend your career on human evolutionary genetics,” recalled Dr. Goldstein, who now studies disease genetics at Columbia University.
“He just listened very politely and wasn’t persuaded an iota,” he added with a laugh. “He wasn’t just proven right. He was proved dramatically right.”
Abandoning medical school, Dr. Reich continued with genetics research and was hired by Harvard Medical School in 2003. By then, he had developed a close partnership with a mathematician named Nick Patterson, who had come late in life to genetics after twenty years working as a cryptographer in British intelligence and then joining a hedge fund.
Dr. Reich appointed Dr. Patterson deputy head of the newly formed genetics lab, and together they began developing new statistical techniques to plumb genetic data for hidden patterns.
The two researchers devised a way to determine whether a single population descended from two or more distinct groups. Collaborating with researchers at the Center for Cellular and Molecular Biology in Hyderabad, India, they put their method to its first big test.
Analyzing DNA from hundreds of villages, they discovered that just about every living Indian descends from two distinct groups. One, which the researchers called Ancestral North Indians, is related to Central Asians, Near Easterners and Europeans.
The second group, Ancestral South Indians, is a mysterious population that is not closely related to any living people outside of India. The two populations mixed together, Dr. Reich estimated, 2,000 to 4,000 years ago.
As Dr. Reich and his colleagues gained attention for their new methods, they got an extraordinary invitation: to study the DNA of Neanderthals.
A Mysterious Lineage
The invitation came from Dr. Paabo. In the 1990s, he had pioneered methods to extract ancient DNA from fossils dating back tens of thousands of years. While he studied many extinct species — such as cave bears, mastodons and ground sloths — Neanderthals were his deepest passion.
Fossils of these heavy-browed individuals date back over 200,000 years in Europe and the Near East. They made tools, weapons and even cave art. But they vanished about 40,000 years ago.
Dr. Paabo gradually filled in gaps to reconstruct the entire Neanderthal genome. In 2006, he invited Dr. Reich’s team to help figure out how modern humans and Neanderthals were related.
Dr. Reich threw himself into the project, and over the next few years, the scientists made a series of landmark discoveries.
The DNA of Neanderthals indicates that their ancestors split from our own about 600,000 years ago. But Dr. Reich’s tests revealed that living humans outside of Africa still carry traces of Neanderthal DNA.
How is that possible? Before Neanderthals became extinct in Europe, they encountered and interbred with the ancestors of modern humans as they departed Africa.
As the scientists searched in more fossils for Neanderthal DNA, they got another surprise. In 2010, a nondescript pinkie bone recovered in a Siberian cave called Denisova yielded the entire genome of a previously unknown, and extinct, lineage of humans.
The Denisovans, as they came to be known, split off from Neanderthals about 400,000 years ago, genetic analysis revealed.
Denisovan DNA has turned up only in a few additional teeth discovered in that Siberian cave. The oldest such fossils date to over 100,000 years old; the pinkie bone belonged to a Denisovan who lived sometime between 48,000 and 60,000 years ago.
Dr. Reich and his colleagues discovered that Denisovans, like Neanderthals, left a genetic legacy in living people, mostly in Australia, New Guinea and Asia.
Their research also suggested that Denisovans divided early in their history into two lineages. “They were isolated from each other for many hundreds of thousands of years,” said Dr. Reich.
Each branch, the new study suggests, interbred with the ancestors of living humans. One Denisovan group left behind DNA in modern-day Asians and Oceanians. The other branch left genetic traces only in living people in China and Japan.