Roundtable

Deeper Than Deep

David Reich’s genetics lab unveils our prehistoric past.

By Ron Rosenbaum

Wednesday, August 23, 2017

David Reich. Photograph by Kris Snibbe / Harvard University.
IMAGE:

 David Reich. Photograph by Kris Snibbe / Harvard University.

“It’s like the discovery of the New World,” David Reich tells me. “Everything is new, nobody’s looked at it in this way before, so how can things not be interesting?”

The excitement surrounding David Reich’s ancient genetics lab at Harvard Medical School is almost palpable. Journals like Science and Nature are unstinting in their praise of the work being done in the Reich Laboratory. Reich and his colleagues are rewriting the history of the human species. Like a scientific Cecil B. DeMille, they are working toward creating an epic cinematic reenvisioning of human history that takes us deep into the mists of the past, tens of thousands of years ago.

In February of this year the forty-three-year-old Reich was named corecipient (with his colleague Svante Pääbo at Germany’s Max Planck Institute) of the $1 million Dan David Prize in archaeology and natural selection for being “the world’s leading pioneer in analyzing ancient human DNA,” which led to the discovery that Neanderthals and humans interbred—“a quantum leap in reconstructing our evolutionary past.”

A discovery, I was to learn from Reich in a conversation that preceded the prize, that had been superseded by even more astonishing developments: evidence of interaction with human and non-Neanderthal variants of hominids, including evanescent but once real “ghost populations.”

This is not “ancient history,” which goes back a few thousand years to the dawn of writing. This is deeper in the past than “deep history,” which takes us even further back—before the invention of agriculture, before the invention of language, before the invention of the wheel.

This is deep, deep history, tens of thousands of years ago. When, it’s now emerging, hordes of humans, vast tribes of variations of hominids—Homo sapiens, Neanderthals, the newly discovered “Denisovans,” the mysterious “ghost populations”—ranged and thronged and clashed and bred and interbred (and probably exterminated large portions of each other) across vast landscapes that were battlefields and graveyards.

It’s deep, deep history that’s beginning to unscroll a vast pageant through the wonders of big data crunching and the analysis of ancient DNA samples from fragments of bone and mummies that have been rotting away in the dusty basements of museums.

Skull of a male aged thirty-five to fifty, Paleolithic period. © The British Museum.

And not only in old bones and mummified objects. The evidence for much of these vast clashes and close encounters is something we carry around within us in microscopic stretches of DNA that are the only legacy left from extinct variant species of humans. In microscopic sequences of chemical bonds on the double helixes of heredity there are traces of ancient variations on human species who lived and thrived and left nothing else behind beyond a few random sequences of chemical bonds. The faintest of faint echoes of a prehistoric past we’re only beginning to grasp. It’s a shift in focus as radical as the one that allowed us to glimpse—through Hubble-era telescopes—the billions of galaxies of the knowable universe and radically shift our perspective on our place in deep space. Suddenly we are able to see in the galaxies of genes within us and the stories they tell of a new way of envisioning our place in the history of the planet. 

And this fellow David Reich, sitting across from me in a corner of his lab on Avenue Louis Pasteur in Boston, this skinny slip of a hominid, David Reich, clad in a T-shirt and slacks—the Zuckerberg couture of Harvard geniuses, you might say—is at the heart of what is likely to be remembered as one of the great scientific revolutions. One unimaginable just a few years ago.

 

To oversimplify enormously, big data number-crunching has revealed that there are stretches of human DNA in Neanderthals and of Neanderthal DNA in humans. We’ve known this for only a little more than a decade.

“When I entered this field,” Reich tells me, “it was still believed that Neanderthals and humans did not interbreed,” he says. “It was a triumphant time for the idea of ‘out of Africa’ migrations of modern humans. And the evidence seemed to point to all people living today being descended from a dispersal out of Africa when they encountered Neanderthals but entirely displaced them without contact or mixture.”

But now we know there was a lot of mixing, mating, hybridized interbreeding.

“Until 2010 the evidence was consistent with there being no Neanderthal impact on modern humans,” says Reich. “That was the context I was walking into. And we were very surprised when the evidence began telling us that in fact Neanderthals had mixed into modern humans.”

“When does this happen?”

“About 50,000 years ago there’s clear evidence of interbreeding between Neanderthals and modern humans from the genetic data, and we have precise dates on it from various papers we’ve written.”

And then, as DNA number-crunching power accelerated, so did an entirely new vision of the past with two—maybe more—new human-like species whose ghostly presence had made Reich a star in genetic science circles.

What Reich’s lab has begun to unveil is that at least two previously unknown humanoid species interbred in the deep past with both humans and Neanderthals but are now extinct. Extinct but survive within us as fragments of ancient DNA code that reflect memories of interactions—let’s be frank, sex—with other hominid variations. Proof of interbreeding and extinctions on a scale that suggest huge dramas—wars, migrations, invasions—we, or really, Reich are only beginning to reconstruct. Just as we are only beginning to reconstruct those lost populations and deal with the realization we have the ability to build a model of the billions of genetic combinations that make up modern humans.

It’s this realization—the kind of work Reich and his colleagues are doing—that makes people nervous about the powers the ancient DNA savants hold over the shape of humans to come. 

The suspicion of dark doings in labs is one that has itself a deep history, still capable of provoking headlines in respectable newspapers that read like this example from the Washington Post, which appeared just a few days before I met with Reich:

SECRET HARVARD MEETING ON SYNTHETIC HUMAN GENOMES INCITES ETHICS DEBATE

We’ll get to this alleged threat—Reich was there at that meeting. But in the headline one detects a hint of age-old fears. Of Dr. Faustus conjuring up the devil Mephistopheles to do a deal for immortal life. Of Dr. Frankenstein creating life in a lifeless-looking human shape.

“Now that we can read the genetic code completely,” Dr. Reich tells me, “it’s understandable if people are concerned we can write it.”

If we can write the entire genetic code—the billions of chemical pairings that make up the molecules that make up the chromosomes that carry the genetic information in the mitochondrial nerve centers of cells—we could, theoretically, replicate human-like beings. Bring the ghost populations back to life in Jurassic-like parks in one imaginary future.

Dr. Faustus, Dr. Frankenstein, Los Alamos—there are reasons to fear the power of labs. But on this sunny spring day, Reich’s lab doesn’t seem like a threat to humanity. It looks like the home base of another kind of explorer looking for new Americas, attuned to a past that—like deep space—we had been blind and deaf to, giving us back our origins.

Indeed Reich seems to be the opposite pole of the mad or bad scientist. One so mild-mannered and soft-spoken I keep having to ask him to speak up into the tape recorder. 

What put him at the center of all these extraordinary developments? The way he describes it, he happened to be in the right place at the right time. With the right genes.

He comes from an extraordinarily gifted family of geniuses. His father, Walter Reich, is one of the world’s foremost scholars of the Holocaust. A savant of the dark side of pseudoscientific genetics and theories about racial history, Walter Reich had been first president of the U.S. Holocaust Museum in Washington, DC. And David Reich’s brother Daniel is a brilliant if skeptical neuroscientist at the National Institutes of Health in Bethesda, Maryland, where—among other things—he studies the origin of what we call evil in that nest of neurons, the brain. 

And so it’s not entirely surprising David Reich’s interest in both history and biology and the rise and fall—and extinction—of racial populations. How genetic differences, the misuse of crude genetics, racial theories, the long hidden history of mass violence in the deep history of human encounters came across his radar as a deep question when he was deciding what branch of science he would focus on.

His description of how he came to focus on ancient genetics suggests he was circling and circling the cutting edge of human sciences for a place of his own.

“I had an amateur interest in history all throughout,” he tells me. “I read a lot of history on the side in school. I started here at Harvard as an undergraduate studying what was called social studies, which is really sociology. Which was sort of supposed to support this interest in history. I switched out of it at the end of my second year into physics, which I’m still interested in. I finished my degree in physics, and I didn’t really do much biology at all when I was in college. But instead of going on to a PhD program, I went to Oxford and took a second bachelor’s degree in biochemistry, and then never completed that. Then I switched to research into genetics and ancient genetics.” He was clearly searching for something, some ultimate mystery to tackle.       

“What was the state of knowledge at that point in the field you’re working in now?”

“This field has been changing very dramatically, and what’s driven it is the technology. So at the time, it was literally a hundred thousand times more expensive to generate a piece of data.”

“A hundred thousand times more expensive?”

“Yes.” Reich explains that computer analysis of the molecules making up the genes that determine hereditary characteristics of humans used to be primitive. Analyzing the molecules that make up the chromosomes that make up the genes for heredity—that specify an individual’s identity, his or her similarity and difference from other members of his or her species—required the ability to “read” billions of different chemical bonds from a tiny sample of DNA. No one could have imagined such analysis possible until computers began increasing their data-crunching power at exponential rates. Before then, says Reich, “we had a hundred thousand times less data, and it was not possible to get any meaningful ancient DNA.”

But almost overnight, in the decade between 2000 and 2010, everything changed a hundredfold. “It’s become possible to look at things that were not possible to look at before,” he says. “So this is a kind of technological-driven revolution. It’s like inventing a telescope. You can see things you couldn’t see before.”

 And the payoff for Reich was to begin to understand—to visualize—a dimension of human history that had been shrouded in prehistoric darkness. To make it possible to imagine a movie, a cinematic depiction of human and hominid ancestors before the time of written epics. Yes, a movie hundreds of thousands years long. A Game of Chromosomes, you might say, played out over eons of unrecorded time. One that has relevance to an age in which migrations and population displacements are hot-button issues.

Geology: satire with a man sleeping in an armchair, dreaming as the skeleton of a bird stands over his head and a mammoth appears before him, 1840s. © The British Museum.

“For me, it’s actually not as much a mystery as a mental image,” says Reich. “The critical thing for me has always been to understand our place in the world, how people in the world got to the way they are today. There is a diversity of people in the world. I would like to understand and hold a picture in my mind of how that diversity and how these people relate to one another today and how it got to be the way it is. I think the goal is really a mapping goal. To actually create a chronicle of how human populations evolved over time to reach their present diversity, how they merged and separated with each other, admixed with each other, and went extinct, in some cases, to achieve the population structure we see today. What is the pattern of all of that?” 

“There’s a vast scroll-like complexity you’re trying to depict with these new tools?”

“Yeah, I think that what we have is just a two-dimensional snapshot of the world, the people we have today, the people living today. They all are two-dimensional because there’s latitude and longitude where these people live, but only one dimension of time. They all live in the present. But there’s a three-dimensional picture you can obtain by not just surveying human variation of the present, which we’ve already got, but surveying it, say, every few hundred years back in time, going back tens of thousands of years. That’s now possible with this technology of ancient DNA. We can make a movie or scroll, moving forward in time.” 

And this, says Reich, might let us know why populations diverge and merge.

“We’re not going to be able to read the Iliads and Odysseys and Rig Vedas and the Judeo-Christian bibles telling exactly how those things happened, because this is the time before writing, but we will document those mergers and splits,” he says. “We’ll know where these people lived.”

Perhaps we can discover how the most ancient of mythological narratives—the Iliads, the Odysseys, ancient testaments—might be echoes of real human populations in mortal combat.

Yes, he says, “moving back to your analogy of the scroll or the movie, the three-dimensional movie, yeah, in my head that’s the image. I think we need to create a picture of our past and how people relate to each other over time, and create a cinematic graphic picture of it that’s much richer than the two-dimensional flat picture we have today.”

The technological advances have helped unveil utterly unexpected discoveries, such as the Denisovans and the “ghost people.”

 

The Denisovans. When I recall Reich’s description of the discovery, it seems almost as if he’d gotten a phone call from a Siberian cave that took fifty thousand years to arrive.

“I was intensely involved with a colleague who runs a laboratory in Germany, a great scientist, Svante Pääbo, who told me that they had through accident sequenced DNA from a finger bone of a girl who lived fifty thousand years ago—it was from a cave in southern Siberia. This individual turned out to have excellently preserved DNA. They were able to obtain data actually better than what we had gotten from Neanderthals. The data showed that this girl was not a modern human. She was an archaic human. She was not a Neanderthal. Different populations. That’s all—we don’t have any morphological information except from one tooth from a relative of hers.”

“One tooth.”

“We have a tooth.”

“Where’d the tooth come from?”

“Same cave.”

“That’s kind of shocking, isn’t it? That this whole realm of human experience might have gone totally unnoticed—”

“Absolutely.”

The DNA analysis was powerful enough to show that the being in the cave was humanoid but not exactly human. And that fragments of code for this variant of human could be found within us now. Even more shocking was the discovery made in Reich’s own laboratory without the aid of a single fragment of bone or tooth—the ghost populations.

They found evidence in DNA samples of now extinct species such as the Neanderthals and Denisovans. But they also found traces of faceless hordes of other humanoid types who roamed the earth hundreds of thousands of years ago. What did they look like, think like? Is it conceivable they were as numerous on the face of the earth as modern humans and Neanderthals?

“I don’t think we know,” says Reich. “They were very widespread because we sampled them from Denisova Cave, which is in the boundary of Mongolia, Kazakhstan, and Russia on one hand. And China. We’ve also lineaged the girl with the little finger bone with the ancestors of New Guineans, who are in tropical Southeast Asia.”

The mind begins to reel listening to and conjuring up these prehistoric hordes, which almost seem to give credence to pre-Noachic narratives in Genesis and the precursors to the Cronus generation of gods in Greek myth.

Do we know why these people became extinct and we survived?

“Yeah, no more reason than why Europeans were successful at peopling the new world than other groups were. The picture in my head is that when modern humans expanded out of Africa they were carrying technologies that allowed them to displace the archaic humans they encountered. I don’t know if it was because they had greater biological capacity.”

In terms of institutions, the DNA discovery was a turning point. Harvard moved quickly to give Reich a lab with his name on it. It’s a pretty expensive, impressive institution.

“Yeah, I mean, this laboratory—we built it in 2013 with Svante Pääbo, and because we wanted to apply the technology invented by Svante in Germany to the last ten thousand years of history, a topic he wasn’t as focused on. So he helped us to do that here. And I focused the whole energy of my laboratory to make that possible.” 

“Focused it in what way?

“I tried to recruit the key people. A lab director in our group is a specialist in ancient DNA. She came from the German group and agreed to work on this with us. We have a group of statisticians and computer experts who help us analyze data, and we have people who study the data, look at population history. So we assembled all under one roof, all the skills we needed to do this type of work.”

“You moved very fast, though. Was there just a recognition this was the place where unprecedented discoveries were going to change the way we think?”

“Yeah, it’s clearly a revolution and it’s clearly a revolutionary technology. It’s obviously transformative to people who are anywhere near this. It’s worth putting a lot of energy into realizing its promise. So that’s what we’re doing. We’re trying to work very hard to implement this technology to make it possible to use it to address interesting problems—as other people are doing—we’re not unique. We’re trying to work as hard as we can, and I’m trying to sort of learn new things about history based on this type of data.”

“Tell me just what your day was like today.”

“I spent the morning corresponding with an archaeologist in Kazakhstan. We’re trying to do genetics in the Bronze Age and the pre–Bronze Age variants in Kazakhstan.”

“Pre–Bronze Age, okay. And when’s Bronze Age?”

“Bronze Age begins about 4,000 years ago and ends about 2,500 years ago. So the Mycenaeans and the Minoans of Greece are Bronze Age peoples. The earliest biblical period is the Bronze Age period. And King David and King Solomon are the beginning of the Iron Age period. The Philistines are the beginning of the Iron Age, which is more technologically advanced.”

“And when is Homer?”

“Homer is writing about the Bronze Age from a later time that was already the Iron Age. It was a technological revolution that’s erupting in Greece, across the Mediterranean.”

“So you’re now corresponding with this guy in Kazakhstan about—?”

“We’d like to characterize the genetic variation in Kazakhstan because it’s a key connection point between the regions south of the Hindu Kush mountains, Iran and India in the south, the steppes in Russia in the north, in China in the East; it’s all mixing up there. And we’re trying to understand the connections. It’s a place of movement and migration, and understanding the genetics is interesting. So that was my morning, and then I spent some hours talking with colleagues today in the laboratory about ancient farmers of Israel and Iran that we have some data from.”

“Ancient farmers of Iran?”

“And Israel from about eight thousand to nine thousand years ago that we have some data from. And then I spent some time talking to a colleague talking about ancient Africans.”

“Where did you get the ancient farmer data from Iran from?”

“From the University of Pennsylvania Museum; there’s bones in the basement, and they drilled those bones and got the DNA from those bones.”

“This is fascinating to me that there have been all these bones in museums all over the world, hiding these clues. The search through dusty museum storehouses must be...” I’m thinking of the ending of Raiders of the Lost Ark, Raiders of the Lost DNA.

He sounds almost greedily anticipatory about “going through these amazing museums which have cellars full of skulls and finger bones and teeth. We are approaching these museums and we are saying, ‘We have this technology that we can apply to your amazing samples, and can you share some samples with us for analysis?’

“And then, later in the day, I went over to the Broad Institute, which is a genome center across the river in Cambridge, and talked about sequencing some of these samples, using more efficient technologies that they’re using. And then after lunch I talked with a scientist in my laboratory about elephants.”

“Elephants?”

“Yes, ancient pachyderms. Mammoths and mastodons—we’re sequencing data from them and seeing how they’re related to each other. After that I talked to another scientist in my laboratory about ancient Chinese history.”

“Wait, what is the significance of the mammoth and mastodons?”

“We have ancient DNA from these ancient elephants. Mammoths and mastodons are extinct, so it’s interesting to see how they’re related to each other and to present-day elephants. That’s what we’re trying to do with the ancient DNA. That’s our only nonhuman project going on.”

The Cohoes Mastodon, c. 1872. © Rijksmuseum.

“And then after that you were about to say…”

“There are scientists in my laboratory working on East Asian population history. We have data from a lot of present-day people from Tibet, from China, different ethnic groups within China, Southeast Asia. Very little is known about East Asian population history in comparison to European and Near Eastern population history, and we’re trying to rectify that. We have a little ancient DNA but not much. Mostly this is modern DNA from present-day people.”

“There must be an enormous quantity of old bones and museums and things like that in China that have yet to be—”

“Prepped.”

“Harvested? Is that…?

“Correct.”

“Does that involve diplomatic approaches or…?”

“There are some places in the world where it’s impossible to get bones from. It’s very difficult to get samples out of China. Getting bones out of China is basically impossible or nearly impossible, because they refuse to export human remains. This type of work needs to be done through collaboration with Chinese scientists if we’re going to get ancient DNA.”

“Are the Chinese aware of this goldmine of information they have?”

“Yes, some are. A scientist in my lab who is a postdoctoral scientist has gone to Beijing to start a laboratory, and she’s trying to do this type of work in China.” 

“What do you think? There are many mysteries obviously, but what is the grail, would you say, of your work? What is the mystery that is most perplexing or, I don’t know, you think might be fruitful?”

“For me, it’s actually not as much a mystery as a mental image. The critical thing has always been to understand our place in the world, how people in the world got to the way they are today.”

Speaking of today, I wondered if he was finding lessons about populations mixing and migrating from studying ancient encounters. “I came across some reference you made in an article about you that spoke of finding ancient East Asians and Europeans living side by side. It seemed to be a hopeful, signifying observation—that it was possible for human beings who are not alike to share the same space.”

“Yeah. Yeah, I think there’s clear evidence of certain places in the world where there are multiethnic societies in the past, kind of like New York City today, that they persisted for extended periods of time without those groups disappearing for some time. For example, in southern Sweden five thousand years ago, there’s evidence of very multiethnic societies, not like a big cosmopolitan place today; there’s not as high a density of people. Or we have a society east of the Urals where there’s evidence of multiethnic societies, variants among peoples in their ancestry that’s quite profound. That has clearly happened in history.”

“So diverse groups are not necessarily doomed to extinguish each other?”

“No, I mean, the more common pattern than extinguishing tends to be mixture. People tend to mix with the people they’re with.”

“Make love not war?”

“Yeah. Attempts to keep groups apart through social structures and traditions are generally unsuccessful for the long term in human history.”

I turn hesitantly to the dark side of the genetic revolution, the one highlighted by the Washington Post story about the “secret Harvard meeting” incited by concern over synthetic human genomes and its revolutionary potential. “There’s been recent concern among bioethicists about just how rapid the ability to create genomes has become. There was some meeting a while ago that dealt with the downside of being able to create and implant genes in humans or viruses.” In viruses the concern is that if genes for illness can be disarmed, they can also be armed up—creating an “arms race” of germ warfare. “What’s your feeling about this whole kerfuffle?” 

“Well, actually the person involved in that is down the hall in this building, but that is a very different branch of genetics from what I do. That is engineering. What I do is inference about the past. I’m just trying to learn about history, and they’re actually trying to modify genomes, so it’s completely different. I’m trying to read genomes; they’re trying to write genomes. It’s a very different thing, and I think it’s one of these modern technologies that is potentially disruptive to our very being. Genetics. You know, the ability to engineer genomes is the biological equivalent of nuclear weapons. It’s really a fundamentally powerful—”

The biological equivalent of nuclear weapons! His concern seems heartfelt. “That’s kind of breathtaking when you think about it. Splitting the atoms, splitting the genome, or whatever…”

“Yeah, yeah, it’s a kind of reversal of things you couldn’t or haven’t done. You couldn’t split an atom apart before nuclear technology, and you could not reverse engineer the genome before modern recombinant genetics. That’s a very powerful thing. It’s a powerful tool, and it could be used—or misused, presumably—used, and abused like other types, like nuclear technology. It’s quite a profound thing.”

“Do we even know the endpoint of that? Could we create life?”

“Presumably.”

“Really?”

“Yes.” 

“You say that casually, and yet—”

“I don’t think life is so special.”

“You don’t think life is so special?”

“No, I mean it’s special, but I think it’s just as obviously [just] biochemistry. Obviously it’s incredibly amazing and wonderful and inspiring and extraordinary that we live in this very complicated world full of amazing lifeforms. However, it’s not surprising that to me the boundary between life and nonlife is just—there’s nothing magical about it. But I do think it’s pretty scary to be experimenting with this stuff.”

“Really?”

“Yeah, personally. To even consider putting these genes into people I think is pretty scary.”

“And you personally feel sort of scared that you’re at the top of this unknown kind of discipline? That who knows? Just like the Los Alamos people who knew what-—”

“Yeah, I think Los Alamos was a bit more immediately dangerous. But genomics has the potential for a lot of abuse, and it has the potential to interfere with things that have never been interfered with before, have never been possible technically to interfere with before. So it’s pretty scary, yeah. People have always been limited by certain biological limitations, a certain amount of energy possible to extract from the world. Now we have new tools available. We can release much more energy than we could than splitting an atom.”

“Should it be regulated?”

“I don’t know. I haven’t thought about it enough—just am aware it’s powerful and easily abuseable.”

“Couple of minutes ago you were just biking across the river in the middle of your day. And you’re carrying all this weight of all this…I mean, do you feel it? I don’t know how I would feel.”

“I think that you probably do, because you’ve probably read about other people who are in the middle of scientific revolutions. I’m one of the people involved in the scientific revolution; I’m not the only one. But you’ve read about people like this before. I don’t know how to judge the importance of this scientific revolution compared to, for example, quantum mechanics or astronomy, telescopes, microscopes, electron microscopes. I don’t know how it relates to the discovery of classical texts in libraries of old monasteries. I don’t know how the importance of this revolution compares to those, but it’s exciting. And I think I’m one of the people engaged in that. So, I don’t know if it’s as much a weight, although maybe that’s how you could describe it; I’m very lucky to be engaged in this activity right now.”

 

Explore Discovery, the Spring 2017 issue of Lapham’s Quarterly.