In fall of 2022, Swedish geneticist Svante Pääbo won the Nobel Prize in Physiology or Medicine for his discoveries concerning the genomes of extinct hominins and human evolution. How has the study of ancient DNA been altered by Svante Pääbo’s work? Elizabeth D. Jones, author of Ancient DNA: The Making of a Celebrity Science, dives into the historical context of Svante Pääbo’s contributions to DNA research in this original piece.
Elizabeth D. Jones—
Svante Pääbo, he is “The Dark Lord of Ancient DNA,” one of his colleagues told me. This is how scientists in the discipline fondly, and sometimes not so fondly, describe Pääbo. With a heavy Swedish accent, his voice is soft and soothing, and it stands in marked contrast to the complete unrivaled power he holds over the field of ancient DNA research. His influence is undoubtedly more predominant now since he won a Nobel Prize for his discoveries of extinct hominins, such as Neanderthals and Denisovans, and for his contributions to understanding human evolution. But Pääbo was not always the paleogenomics powerhouse that he is today. So let us go back to the start of the field, back to the 1980s when the idea of recovering DNA from long-dead organisms was very much in the realm of science fiction.
It is 1984. Allan Wilson is a professor at the University of California, Berkeley, and a pioneer in molecular evolutionary biology. He and his colleagues have just extracted and sequenced DNA from Equus quagga, an extinct zebra-like relative of the horse from southern Africa. The amount of DNA is small, just two hundred and twenty-nine base pairs in length, but it is old, nearly one hundred and forty years old, and a real feat because it is the first time DNA has been extracted from an ancient and extinct creature. They submit a paper on their novel findings to Nature. While they wait, they look for further funding to investigate the phenomenon in hopes of establishing a new way to study evolutionary history.
The same year they recover DNA from the quagga, Wilson and his colleagues write a grant for the National Science Foundation to search for DNA from the mammoth, the moa, insects preserved in amber, and more. The proposal is the first of its kind. If awarded, it will help found the field of molecular paleontology and specifically, the field of ancient DNA research. It is rejected. “I am not convinced that selection of these organisms will demonstrate the universal applicability of recombinant DNA technology to systematic evolutionary studies,” says a reviewer. “However, at one time it was common knowledge that the earth was flat and the moon was made of green cheese.” Another shares a similar skepticism, writing, “I refuse to gaze into a crystal-ball and reject the possibility a priori. It is clear that looking for fossil DNA is worth the trials and tribulations, particularly if so distinguished a researcher as Wilson wishes to undergo the trauma.” A third reviewer is much more cynical: “Discovering and extracting DNA from fossil species is a very interesting and technically difficult biochemical feat, but it is certainly not clear to me how this approach will broaden our perspective on any major evolutionary problems.”1
Enter Pääbo. It is 1984, and he is a graduate student at the University of Uppsala in Sweden. He is pursuing a doctorate in molecular biology but also using his free time to conduct some pretty strange experiments. Pääbo wants to extract DNA from ancient Egyptian mummies, so he sets out to replicate the mummification process by putting a small bit of liver he purchased from the store into the oven in the lab, then heating it up to extremely high temperatures. The smell is revolting, he is scared his supervisor will find him out, but he is able to extract DNA, suggesting in theory that dehydration via the mummification process might preserve genetic material. He moves on from the liver to actual mummy specimens. It is a far from easy task, but in the end, he is seemingly successful at recovering DNA from several mummy remains that are nearly two thousand years old. He publishes his results in an East German journal, Das Alterum, in 1984. There is absolutely no fanfare, likely due to low readership. He submits again but this time to the Journal of Archaeological Science, but it turns out to be a slowly moving review process. Meanwhile, Pääbo reads a report in Nature on the recovery of one-hundred-and-forty-year-old DNA from the quagga.2 He immediately writes a third and final paper on his mummy results and sends it to Nature.3
As Pääbo recalled in his tell-all account of his life, he was thrilled that a prominent scientist like Wilson was pursuing the same sort of research. He excitedly and nervously sent him a copy of his paper. Wilson wrote Pääbo back, asking if he—Allan Wilson—could spend a year in Pääbo’s lab to do ancient DNA research. Wilson honestly, and rather humorously, had mistaken him for a professor when he had yet to finish his doctorate. So Pääbo replied, explaining the situation and asking if instead he could join Wilson in Berkeley, after graduation of course.4
From Wilson’s lab, Pääbo went on to become one of the up-and-coming superstars of ancient DNA research, starting his own lab in 1990 at the University of Munich, then becoming Director of Evolutionary Genetics at the Max Planck Institute of Evolutionary Anthropology in Leipzig before the end of the decade. Over these years, Pääbo and his lab (along with other labs) became ardent proponents of ancient DNA research as well as gatekeepers, setting the standards, scale, scope, and pace of the rapidly-growing and media-frenzied field. As excited scientists joined the hunt for ancient DNA, Pääbo became a regulator and a researcher within it. He took it upon himself to address the constant concern for contamination and need for proof of ancient DNA authenticity, especially in light of a series of extraordinary publications on the recovery of multi-million-year-old DNA from amber insects to dinosaur bone. Pääbo policed the discipline through advocating for criteria and sometimes demonstrating evidence that others’ results were the outright product of contamination. Pääbo promoted a conservatism via hardline devotion to criteria of authenticity and by deliberately separating his work from what he viewed to be less credible work in the field. This conservative philosophy shaped how Pääbo, his students, colleagues, and collaborators influenced the trajectory of the field, then and even now.
Today, Pääbo’s conservatism for rigorous and reliable science is clearly coupled by a somewhat contradictory (but remarkably successful) mission to go above and beyond what anyone thought possible regarding genetic evidence for human evolution. In 2010 Pääbo and his lab sequenced the Neanderthal genome, thanks to a furiously competitive race to be the first to do so. He also discovered a previously unknown hominin, Denisova, identifiable from DNA from a very small finger bone. On top of that, he has revealed how genes have been transferred from extinct hominis to extant humans, illuminating our understanding of human origins, evolution, adaptation, and migration over thousands of years. These findings have held profound implications for understanding our own immune systems, specifically how and why some people are more or less susceptible to infections thanks to the flow of genes from our ancient ancestors. While he may be “The Dark Lord of Ancient DNA,” Pääbo’s insanely ambitious endeavor to know our past is clearly lighting the way for our future. And he has a Nobel Prize to show for it.
Elizabeth Jones is a historian of science and postdoctoral research scholar at North Carolina State University and the North Carolina Museum of Natural Sciences in Raleigh.
Citations
1 Allan Wilson, “Molecular Paleontology: Search for Fossil DNA,” National Science Foundation Grant Application (1984): 1505–58.
2 Svante Pääbo, Neanderthal Man: In Search of Lost Genomes (New York: Basic Books, 2014).
3 Russell Higuchi et al., “DNA Sequences from the Quagga, an Extinct Member of the Horse Family,” Nature 312, 5991 (1984): 282–84.
4 Svante Pääbo, Molecular cloning of Ancient Egyptian mummy DNA. Nature 314 (1985): 644–45.
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