QnAs with Svetlana Mojsov, Joel Habener, and Lotte Bjerre Knudsen: Winners of the 2024 Lasker~DeBakey Clinical Medical Research Award

When the long-awaited results of a clinical trial of the wildly popular weight loss drug semaglutide were published in late 2023, the moment marked a milestone in cardiovascular medicine.A once-weekly injection of semaglutide slashed the incidence of death from cardiovascular causes and nonfatal heart attacks or strokes in nondiabetic patients with a history of heart disease as well as obesity or overweight ( 1 ).Only two years earlier, semaglutide, a type of drug called a glucagonlike peptide-1 (GLP-1) receptor agonist, had won approval from the US Food and Drug Administration for treating obesity, transforming the treatment of an epidemic poised to afflict more than half of the global population by 2035 ( 2 , 3 ).The origin story of GLP-1 receptor agonists, which act on the brain to regulate appetite and food intake, can be traced back to the mists of early 20th-century science on human gut hormones.Decades of research underpin the development of this class of drugs, the discovery of which was inspired by the search for "incretins," which are hormones that regulate blood glucose levels by triggering insulin release after a meal.From the initial discovery of the gene for GLP-1 hormones in the DNA of anglerfish to the successful development of GLP-1based drugs for the treatment of type 2 diabetes and obesity, dozens of researchers played key roles in a sumptuous tale of scientific sleuthing and invention.Three of them have won the 2024 Lasker~DeBakey Clinical Medical Research Award for their singular contributions and sharply observed insights.The winners played a central role in discovering GLP-1 hormones, unraveling their intricate mechanisms of action, and developing effective drugs for diabetes, obesity, heart disease, and a growing list of human ailments: Joel Habener, of Harvard Medical School, and Svetlana Mojsov, of Rockefeller University, for identifying and characterizing GLP-1 and its role in glucose metabolism, and Lotte Bjerre Knudsen, of the Danish drug company Novo Nordisk, for developing a stable and longacting version of GLP-1-based drugs.PNAS spoke to the trio about their plodding path to success as well as the protean power of the drugs they helped bring to patients.[The tangled history of research on GLP-1 receptor agonists features several players that no single award can satisfactorily capture.For a comprehensive history of the underlying science, see here ( 4 ), here ( 5 ), here ( 6 ), and here ( 7 )]. PNAS:A wealth of foundational work prefaces the saga of GLP-1-based drugs, but one point of entry into the sprawling story is the 1982 PNAS article reporting the cloning of the gene for proglucagon.How pivotal was this paper (8)?