To the man who gave us the Neanderthal genome, the Nobel Prize in Medicine.


Svante Pääbo, from the Max Planck Institute for Evolutionary Anthropology, was the sole recipient of the Nobel Prize in Physiology or Medicine on Monday. Readers of these pages will be aware with Pääbo’s work; he was a major force in the completion of the Neanderthal and Denisovan genomes, and his contributions to our understanding of the genetic contributions of these lineages to the genomes of modern humans have been widely reported. A cursory examination belies the depth of information about human anatomy and physiology and medical treatment that this provides.

Even though the Nobels have a long history of controversy about who gets acknowledged, Pääbo’s central involvement in this story and his intensive emphasis on this topic are likely to allow general acceptance of his sole-recipient status. Pääbo’s thoughts were greatly aided by the advent of cutting-edge DNA sequencing technology, but he also had the good fortune to be living at the proper time.

Back in the 1990s, when we were both employed at Berkeley, I had the opportunity to briefly meet Pääbo. Early on in his career, he had shown an interest in ancient DNA and was employed at a top lab devoted to the study of such things that had been founded by the late Allan Wilson. Less than a decade had passed since PCR’s commercial release, and Wilson’s lab was already testing its limits in order to obtain very old DNA that was a rare component of a sample that might have been in the environment for centuries. At the time, moa bird egg fragments were common visitors to the lab.

However, this was before the advent of the genome project, thus obtaining sequences from that DNA took a week of building up thin polymer gels the size of a small desk, exposing X-ray film for many days, and then painstakingly interpreting the film by sight. To finish huge genomes, people did the arithmetic and realised we’d need new DNA sequencing equipment; they debated possible solutions.

Without the efforts of innumerable people who created new generations of DNA sequencing machines, Pääbo and his coworkers would not have been able to achieve their final goals. And without the finished human genome, he wouldn’t have known what sequences to even look for. However, this does not negate the fact that he and his team made significant strides in extracting ancient human DNA sequences. Being engaged in an issue where some of the technical difficulties that inhibited progress were on the edge of being overcome for unrelated reasons was also a stroke of serendipity.

Pääbo has an impressive resume of achievements. It was largely thanks to his efforts that we were able to piece together the first complete image of the Neanderthals as a people, complete with an idea of how many there were, where they had travelled, and which populations had interbred. His subsequent work, which included deciphering the Neanderthals’ entire nuclear genome, demonstrated the numerous ways in which they were distinct from humans. However, these differences were insufficient to prevent their ancestors from mating with our own.

The most startling discovery, however, was that Neanderthals really shared the world with other modern human populations. We were completely unaware of the Denisovans, and our knowledge of what they might have looked like is limited at best. And yet, we have their genome, and it proves conclusively that they interbred with our own ancestors.

This award is in the field of medicine or physiology, so that’s a wonderful connection to make. The Denisovans may have been the ancestors of modern humans, as they were the ones who adapted to the high heights of the Tibetan Plateau. Pääbo and his team have also uncovered a number of alterations that occurred between Neanderthals and modern humans, which may account for differences in anything from the number of neurons in specific brain regions to how we respond to certain infections.

For instance, a 2016 study based on his work indicated that Neanderthals and Denisovans contributed to modern humans’ innate immune responses by passing down three key genes. Genes for toll-like receptors, proteins that bridge cell membranes and are able to recognise conserved, characteristic molecules of bacteria and stimulate immune response, are encoded by these genes; however, these proteins are also associated with allergies.

In addition, a high-coverage Neanderthal genome was released in 2018 by Pääbo and coworkers using DNA from skeletal remains discovered in a cave in Croatia. Data analysis revealed a wide range of gene variants prevalent in the modern human population, including those related to plasma levels of LDL cholesterol and vitamin D, eating disorders, visceral fat buildup, rheumatoid arthritis, schizophrenia, and the response to antipsychotic medicines. Pääbo and coworkers noted, “this adds to accumulating evidence that Neanderthal ancestry increases disease risk in modern humans, notably with respect to neurological, psychiatric, immunological, and dermatological characteristics.” While further research is necessary to completely grasp the role of these genes, Pääbo’s discovery paved the way.

Working with ancient DNA is now pretty common, and many laboratories beyond Pääbo’s are looking at extinct species across the tree of life. For example, we can now position mammoths and mastodons on the elephant family tree. It is hardly an exaggeration to state that it has completely changed the face of biology, making feasible issues that were before unanswerable.

Pääbo, on the other hand, had the perfect combination of timing, location, and passion to play a significant role in the development of the field. And by picking the most striking targets—ourselves and our closest relatives—he has captivated the public’s imagination by explaining our origins.

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