Many Nobel speculators thought Physiology or Medicine would go directly to COVID-19 discoveries, but a different branch of evolutionary research took top prize.
Swedish geneticist Svante Pääbo joined a rare group this morning: not just of Nobel Prize winners, but of “family Nobels”. His father, Karl Sune Detlof Bergström, shared the 1982 Nobel Prize for Physiology or Medicine with Bengt I. Samuelsson and John R. Vane, for work related to local-tissue hormones, or “prostaglandins”. Forty years later, that award went solely to Pääbo, for his contributions to paleogenetics, including work on early and extinct hominins. To date, there have only been eight other parent-child Nobel prize pairs, with the Curies still holding the record for the most Nobel Prizes (five) in one family.
But after a whirlwind of scientific advances in the wake of COVID-19, many seasoned Nobel Prize predictors didn’t see this winner coming. (A gentle reminder that such prizes never reflect the fullness of scientific progress. Nor should scientific progress be measured in awards received or passed over.) Two obvious top contenders, Katalin Karikó of BioNTech and Drew Weissman of Penn Medicine, were highly acclaimed in recent years for their decades-long work with mRNA, which took related research from an overlooked (and even dismissed) field of inquiry to pandemic-curbing COVID-19 vaccines, among other recent fruits of the discipline.
Pääbo’s research, conversely, shed light on extinct hominins like the Denisovans, but only after first helping to develop a methodology that allowed scientists to sequence the Neanderthal genome. This was once considered impossible because the shrivelled remnants of these ancient populations only held short fragments of DNA: a jigsaw puzzle made more challenging by microbial contaminants.
The selection process for Nobel Prizes is a guarded secret, with votes sealed for 50 years, but speculators look to a number of industry factors to predict winners. One is the acquisition of other prestigious awards. Another is how often key papers were cited by peers, with a strong bias toward longevity rather than novelty in the fruits of specific discoveries. Science-data analyst David Pendlebury told reporters that Pääbo’s most-cited paper, from 1989, was cited 4,077 times, and that “[o]nly some 2,000 papers out of 55 million published since 1970 have been cited this many times.”
1989 was a fruitful publishing year for Pääbo, and his most groundbreaking discovery can be found in “Ancient DNA and the Polymerase Chain Reaction: The Emerging Field of Molecular Archaeology” (The Journal of Biological Chemistry). This paper outlines the process that made recovering ancient DNA possible. If you’re looking for a deeper dive into some of the science behind this year’s win, here’s a key summary:
The polymerase chain reaction (PCR)’ can amplify preselected segments of DNA up to quantities which permit direct sequencing, starting from extremely small amounts of DNA or even single molecules … PCR is an ideal tool to amplify a small number of intact ancient DNA molecules present in a vast excess of damaged molecules. In addition to its ability to detect extremely small quantities of DNA, PCR has the advantage of being an in vitro system, which has no capacity for repair or misrepair. … [D]uring enzymatic amplification, most damaged molecules will either not be replicated at all … or will be at a replicative disadvantage … Intact molecules will thus amplify preferentially. Some damaged molecules will of course have only minor lesions, such as deaminated bases. … However, since each error is specific to one molecule in the starting population (and its descendants), its contribution to the result … is likely to be negligible. Such errors would be encountered only if one were to clone individual molecules from the final population before carrying out the sequencing reactions (30,31). An additional advantage of PCR is that its speed allows for easy reproduction of results.
But other papers published in part by Pääbo in 1989 also inform his legacy, because this methodology wasn’t just applied to early hominins. Researchers interested in ancient DNA of other extinct animal species were also quick to make use of the new tool. Pääbo’s research has also explored the possibilities of recovering ancient DNA in plant life, though his primary focus, after establishing the Max Planck Institute for Evolutionary Anthropology in 1997, has been the cultivation of an interdisciplinary approach to the history of humankind that can also help us better understand the physiological underpinnings of our species today.
Although Pääbo was once skeptical about his research informing cloning projects for ancient and extinct species, private enterprises today are building on genome-recovery methodologies to pursue just such ambitious and ethically complex aims.
However, his research also informs our understanding of COVID-19—so perhaps this year’s Nobel Prize for Physiology or Medicine wasn’t far afield of predictions after all. In 2020, Pääbo and Hugo Zeberg (first author) published an article in Nature, titled “The major genetic risk factor for severe COVID-19 is inherited from Neanderthals”. As Zeberg explained, “It turns out that [a specific] gene variant was inherited by modern humans from the Neandertals when they interbred some 60,000 years ago. Today, the people who inherited this gene variant are three times more likely to need artificial ventilation if they are infected by the novel coronavirus Sars-CoV-2.”
As ever in evolutionary sciences, different veins of research into our biological selves have a tendency to converge in surprising ways. Pääbo’s Nobel win on October 3 abundantly illustrates how the study of our ancestors continues to inform the quest for better human and environmental outcomes here and now.
The Nobel Prize for Physiology or Medicine is the first Nobel in this year’s series, which will continue to announce winners on separate days through October 10.