The Nobel Assembly at Karolinska Institutet

Victor Ambros and Gary Ruvkun recount how studies of developmental timing in the nematode C. elegans revealed a new mechanism for regulating genes. The lectures follow the genetic analysis of lin-4 and lin-14, the discovery that a regulatory gene could produce a short non-coding RNA, and the connection between that RNA and complementary sequences in a target messenger RNA. They then examine how the discovery of additional microRNAs, including conserved regulators, changed a seemingly specialised worm finding into a widespread principle of gene regulation. The programme explains how small RNAs influence protein production after transcription and how experiments in a model organism exposed a regulatory system important across multicellular life.

Katalin Karikó and Drew Weissman explain the scientific development of messenger RNA as a therapeutic platform. Their lectures address why laboratory-produced RNA can trigger inflammatory responses and how modification of its nucleosides changes immune recognition and improves protein production. The programme connects those molecular findings with the practical challenges of making RNA stable and delivering it into cells, including lipid-nanoparticle formulations. It follows the development of modified mRNA from a difficult experimental material to a foundation for vaccines and other therapeutic strategies. The lectures cover both the discovery of the relevant RNA biology and the engineering needed to make that biology useful for inducing desired proteins and immune responses.

Svante Pääbo explains how DNA recovered from ancient remains opened an experimental route to studying extinct human relatives. The lecture follows the technical challenge of extracting reliable genetic information from small, degraded and contaminated samples, through the reconstruction of Neanderthal genomes and the identification of Denisovans. Comparisons with living people reveal interbreeding between archaic hominins and the ancestors of present-day humans. Pääbo connects those findings to questions about human origins, the genetic changes that distinguish modern humans, and the continuing biological effects of inherited archaic variants. The account shows how methodological advances in paleogenomics changed both the history of human populations and the questions that can be asked about human biology.

David Julius and Ardem Patapoutian investigate how physical features of the environment are converted into signals that cells and nervous systems can use. Julius describes the use of compounds such as capsaicin and menthol to identify ion channels involved in heat, cold and pain, linking molecular properties to sensory physiology. Patapoutian explains how experiments on mechanically sensitive cells led to the discovery of PIEZO channels and their roles in detecting force. The lectures connect the search for individual molecules with broader questions about touch, body position and the sensing of mechanical conditions within organs. Together they explain the experimental strategies behind identifying temperature and force receptors, and how these discoveries changed the study of sensation.

Harvey Alter, Michael Houghton and Charles Rice recount how an unexplained form of transfusion-associated hepatitis became an identifiable and treatable viral infection. Alter’s clinical and transmission studies distinguished non-A, non-B hepatitis from the known hepatitis viruses. Houghton’s molecular approach isolated genetic material from the elusive agent and enabled tests for hepatitis C infection. Rice’s experiments with viral RNA established that the newly identified virus could itself cause hepatitis and helped make its replication experimentally tractable. The lectures connect these complementary approaches to the development of safer blood supplies, experimental models and antiviral medicines, while showing how clinical observation, molecular cloning and causal experiments contributed different pieces of the discovery.