Looking Back to the Future

$15.5 million grant galvanizes ancient DNA research, collaboration

By STEPHANIE DUTCHEN June 26, 2019 Research

Three brown skulls against a dark background — Ancient bones, such as these skulls from a site in what is now the Czech Republic, provide genetic material that enriches our understanding of human evolution. Images © Martin Frouz and Jiří Svoboda

Ancient DNA research has exploded onto the scene in the last decade, churning out insights into the human past—from Neanderthal ancestry to the identification of “ghost” populations to genetic shifts that accompanied the transition from hunting and gathering to farming—that both enrich and challenge what we know from established fields such as archaeology and linguistics.

The work has raised a host of new questions regarding what ancient DNA can tell us not only about our past and present but also our future, as well as how the field itself can evolve in the most effective and ethical manner.

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Now, Harvard Medical School has received a $15.5 million grant from the John Templeton Foundation—one of the largest awards in the foundation’s history—to lead the ancient DNA community in exploring these questions.

The Ancient DNA Atlas of Humanity, led by David Reich, professor of genetics in the Blavatnik Institute at HMS, will quintuple the number of published ancient human genome sequences, creating a database of 10,000 individuals spanning 50,000 years.

Such a database “would not have been possible to create by other means,” said Reich.

He added that the grant is “a grand bet” on the power of ancient genomics “to enhance and deepen our understanding of who we are and how we’re related to one another.”

The main goal of the initiative is to expand the study of human evolution and the origins of disease, including how genetic changes in the past have shaped present-day disease susceptibility.

Initiative leaders also hope the results will illuminate “humanity’s capacity to adapt in the face of changing environmental conditions” such as climate change, said Kevin Arnold, senior program officer at the foundation.

The effort will leverage funding from additional organizations, including the Howard Hughes Medical Institute, the Paul Allen Foundation and the National Geographic Society. While largely based at HMS, it will also support work in the Human Evolutionary Biology Department in Harvard University’s Faculty of Arts and Sciences, the Broad Institute of MIT and Harvard, and the Department of Anthropology at the University of Vienna in Austria.

Finding the best way forward

Of the grant money, $500,000 is earmarked for efforts to ensure widespread access to ancient DNA data, foster productive conversations with related fields and tackle some of the thorny issues geneticists have been wrestling with.

For example, although some studies have been conducted in areas such as Africa, Southeast Asia, Austronesia and the Americas, most ancient DNA analyses have concentrated on Europe. How can research be spread more evenly across the globe?

The initiative intends to “help fill in the gaps for regions that have been relatively understudied,” said Matthew Walhout, vice president of natural sciences at the foundation.

Researchers are also struggling to find a balance between protecting ancient human remains and analyzing as many samples as they can in order to build large data sets that yield greater insights into past and present human populations.

“We want to handle ancient remains in a respectful and ethical way that preserves material for the future while also recognizing that these unique treasures won’t be around to analyze forever, as the fire at the Brazil National Museum tragically reminded us,” said Reich. “One place we can learn from is archaeology, which has developed methods to excavate sites while leaving parts untouched for future research questions and techniques.”

We want to handle ancient remains in a respectful and ethical way that preserves material for the future while also recognizing that these unique treasures won’t be around to analyze forever.

David Reich

Many questions center on how best to partner with cultures around the world and navigate sensitivities about when and how to analyze the remains of people’s ancestors and how to interpret the results.

“What do we do when science is in tension with cultural narratives, including people’s origin stories? How can we honor the perspectives of all stakeholders while also fulfilling our duty to write papers in rigorous ways?” asked Reich. “As scientists, we are dedicated to the imperative of uncovering the truth, but we also need to recognize that when it comes to issues of identity, what objectively happened can be less relevant than tradition and perception.”

Also looming large is the question of how geneticists who focus on ancient DNA can collaborate more effectively with other researchers, including archaeologists, anthropologists, linguists, historians, museum curators and molecular biologists.

“People are engaging in increasingly complex discussions as disciplines converge and collide,” said Reich. “Although they can be volatile at times, it’s helpful to engage in these conversations for many reasons. For instance, we need to know when certain terminology that is neutral in one field has a history of misuse in another.”

Enhancing current efforts, the dedicated funding will allow Reich and colleagues to convene annual interdisciplinary meetings to discuss existing and emerging challenges. The goal is to publish materials outlining agreed-upon best practices.

“Collaboration is the future of this field,” Reich added.

Already, the grant has allowed Reich’s group to bring on an ethics and outreach officer, an archaeologist who was previously a part-time affiliate of the lab.

The Atlas itself will be free for researchers around the world to use, so that the entire community can dive into the coming flood of ancient DNA sequences.

The database “is designed to uphold the highest standards of transparency, including best practices in open materials and open access, so that the project will be a democratizing force that brings lasting benefit to scholars and researchers in a range of fields,” said Arnold at the Templeton Foundation.

Productive partnership

The grant emerged from more than two years of discussions that ultimately identified a galvanizing area of overlap between the two institutions’ missions: to alleviate future suffering through research, the project leaders said.

“We are focused on conducting rigorous, ambitious, cutting-edge science that explores humanity’s place in the world and isn’t afraid to challenge existing paradigms,” said Reich.

The initiative, along with the whole endeavor of ancient DNA research, is endlessly “exciting and challenging,” he added. “I can think of no better model for this initiative and indeed my own career than that of a midwife, ushering this new field into being.”