Christian De Duve (1917–2013) Biologist Who Won a Nobel Prize for Insights Into Cell Structure

COMMENT OBITUARY Christian de Duve (1917–2013) Biologist who won a Nobel prize for insights into cell structure.

he path to excellence in experimental macromolecules taken up by the cell? biology is long and arduous. Christian To answer these questions, he used an early de Duve was one of the few to reach version of an ‘-omic’ approach. He combed Ta summit that opened new vistas onto the literature for other known hydrolytic uncharted territories. In 1974, he shared the enzymes and, after several reassuring find- Nobel Prize in Physiology or Medicine with ings, went public with the concept of the Albert Claude and George Palade, for their lysosome (C. de Duve et al. Biochem. J. 60, discoveries “concerning the structural and 604–617; 1955), now known as the hub of functional organization of the cell”. the cell’s digestive system. Using similar De Duve was born in 1917 near London, approaches, his laboratory also discovered

where his parents, of Belgian–German the peroxisome, a cellular compartment INGBERT GRUTTNER/THE ROCKEFELLER UNIV. ancestry, had moved to escape the First containing enzymes involved in oxidation. World War. Soon after the war ended, the Thereafter, others discovered lysosomal family returned to Antwerp in Belgium, and peroxisomal diseases. Some of these where Christian attended school — at disorders, in which one lysosomal enzyme is which he excelled. He then enrolled as a either missing or faulty, can now be treated medical student at the Catholic University of by providing the requisite lysosomal enzyme. Louvain in 1934 and joined its physiology Next, de Duve expanded and consoli- laboratory, directed by J. P. Bouckaert. In dated these findings and established him- 1943, he married Janine Herman, who sub- self as a skilled administrator. He directed sequently became a noted painter. She stead- a lab at Rockefeller University (1962–87) fastly supported him throughout the rest and founded and ran (1975–85) the Inter- of her life. His many moves required huge national Institute of Cellular and Molecular sacrifices from her and their four children, Pathology in Brussels (a prescient realiza- and gave de Duve the freedom to focus his Using the high-speed centrifuge, Claude tion of the idea of translational medicine), efforts on scientific research. and his collaborators managed to separate subsequently named the de Duve Institute. During these years, de Duve made several and enrich various cell components on the He also had a principal role in creating the respectable discoveries about storage and basis of their size and density. prestigious and unique L’Oreal–UNESCO retrieval of the body’s principal fuel, glucose, Heading his own laboratory in Louvain, Awards for Women in Science, presented to as affected by the pancreatic hormones insu- de Duve continued research on insulin and one woman annually in each of five conti- lin and glucagon. After the Second World glucagon, this time inspired by Claude. nents. In the last ‘contemplative’ period of War, top-notch international laboratories Among his first observations at Louvain was his life, he wrote influential books directed at opened their doors to him. He first went that the enzyme activity of glucose-6-phos- the educated lay public, primarily on biology to Hugo Theorell’s lab at the Nobel Medi- phatase was mostly associated with a cell and evolution. cal Institute in Stockholm and then to Gerty fraction that sedimented at high centrifugal As de Duve wrote in his memoirs, Sept vies and Carl Cori’s lab at Washington University forces. More detailed analyses by de Duve, en une (Odile Jacob Sciences, 2013), he was in St. Louis. and by Philip Siekevitz and Palade, estab- a precocious child, perpetually the best stu- In 1947, family ties enticed de Duve to lished glucose-6-phosphatase as the first dent (‘primus perpetuus’) in his school except return to Louvain as a professor in its medical ‘marker’ enzyme for the endoplasmic reticu- for one year, when he was declared out of school. On his way back from St Louis, he lum. These findings supported the idea that competition (‘hors concours’) so that another stopped at the Rockefeller Institute for Medi- the cell contains distinct compartments with student could come top. These early acco- cal Research (now Rockefeller University) in characteristic enzyme activities. lades, and the many that followed, reinforced New York for a life-changing meeting with De Duve promptly set his insulin research an inherent sense of self-confidence that his countryman Albert Claude. aside to search for these uncharacterized sometimes had unintended consequences. Claude had gone to Rockefeller in 1929 cellular compartments. Because it could be He emphatically denied having been an to isolate what we now know as the Rous readily measured, he chose the enzyme acid authoritarian boss (‘patron autoritaire’), but sarcoma virus. On route to this goal, he phosphatase. His observations — which to in a typically de Duvean way admitted, in revolutionized cell research by experiment- most contemporaries would have seemed brackets, that some people may feel differ- ing with two recently developed instruments: trivial curiosities related to this enzyme’s ently. Personally, he struck me as a warm, the electron microscope and the high-speed activity and its cellular partitioning, and humorous and compassionate human being, centrifuge. The electron microscope enabled thus not worth close attention — became whom I will miss thoroughly. ■ Claude, with Keith Porter, to look inside cul- important clues for de Duve. Could acid tured cells at a magnification much greater phosphatase be a marker enzyme for yet Günter Blobel is professor of cell biology than that possible with a light microscope. another cellular compartment? Perhaps and a Howard Hughes Medical Institute Their epochal discovery, reported in 1945, the enzyme was part of a cell’s diges- investigator at the Rockefeller University, was the lace-like network surrounding the tive quarter, stored with other hydrolytic New York, USA, where he knew de Duve. cell’s nucleus, the ‘endoplasmic reticulum’. enzymes to break down the multitude of e-mail: [email protected]