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Home , Albert Claude, Christian de Duve, Hugo Theorell, Physiology

Obituary A Feeling for the : (1917–2013)

Fred Opperdoes* de Duve Institute and Universite´ Catholique de Louvain, ,

Christian de Duve was an internationally After the war, de Duve developed an renowned cell whose serendipitous interest in to gain a better observation while investigating the workings understanding of the exact mode of action of led to groundbreaking insights of insulin and . But his knowledge into the organization of the cell. The of was still limited, so he observation, which he once described as decided to widen his horizons. He certain- ‘‘essentially irrelevant to the object of our ly must have had a gift for selecting the research,’’ ultimately led him to discover very best laboratories of those days. First, two —the and the he spent almost a year in ’s —for which he shared the Nobel laboratory at the Nobel Medical Institute Prize in or in 1974 in ; subsequently, he crossed the with and George E. Palade. ocean and went to Gerty and Carl Cori’s Born in 1917 in the United to laboratory at Washington University in St. Belgian parents who had fled the devasta- Louis where he also had the opportunity tion of the Western Front during the First to collaborate with Earl Sutherland. Later, World War, de Duve spent his early in all four would become the village of Thames Ditton near Lon- winners. The Nobel Prize for Physiology or Medicine was received by Carl and don. After the war, in 1920, he and his Christian de Duve, age 95, presenting family returned to Belgium and the young Gerti Cori in 1947 for their research on his ideas on the origin of the eukaryotic Christian went to school in the Flemish metabolism, Hugo Theorell in cell (October 2012). Image credit: Julien city of . He embarked upon his 1951 for his discoveries on oxidation Doornaert. career as a researcher when he enrolled as , and Earl Sutherland in 1971 doi:10.1371/journal.pbio.1001671.g001 a medical student at the francophone for the discovery of cyclic AMP. branch of the Catholic University of In 1947, de Duve returned to Belgium to acid phosphatase, which he assayed as a Louvain in Belgium (1934–1941). He take up the position of professor at the control during these studies, was could speak four languages, a skill that in Louvain and to continue latent—it could be activated by various would later help save his life. his research on insulin and glucagon. treatments, all of which affected membrane de Duve decided to specialize in endo- Beginning in 1950, however, he devoted integrity. crinology and joined the laboratory of the himself more and more to subcellular Together with his collaborators in Belgian physiologist J. P. Bouckaert, where biochemistry, a new field that he would Louvain, de Duve concentrated on refin- he started his research under the difficult pioneer together with Albert Claude ing the techniques of differential and circumstances of the Second World War and George Palade, both in New York. isopycnic for separating cell when facilities and financial support for This change of direction was inspired by constituents, which had been developed by were very limited. Drafted a chance observation that would change Albert Claude at the Rockefeller Institute by the Belgian army, he served as a our understanding of the structural and (now ) in New York, medical officer in where he was functional organization of the cell: de to isolate the various cellular compart- taken by the Germans. Duve noticed that the activity of the ments and to establish their contributions Thanks to his excellent knowledge of enzyme -6-phosphatase was mostly to cell metabolism. Using this approach German and Flemish, de Duve was able associated with a sedimentable cell fraction while working at the Catholic University to outwit the enemy and escape back to called microsomes, which mainly contained of Louvain in 1955, de Duve and Belgium, where he immediately returned vesicles of the . collaborators reached the conclusion that to his research. (Subsequent analyses established glucose-6- acid phosphatase and other hydrolases As a young researcher, he initially phosphatase as the ‘‘marker’’ enzyme for with an acid pH optimum were enclosed concentrated on the storage and retrieval the endoplasmic reticulum.) Oddly enough, in a new , which they proposed to of glucose, the ’s principal energy source, which is regulated by the pancre- Citation: Opperdoes F (2013) A Feeling for the Cell: Christian de Duve (1917–2013). PLoS Biol 11(10): atic insulin. In doing so, he e1001671. doi:10.1371/journal.pbio.1001671 discovered that a commercial preparation Published October 1, 2013 of insulin happened to be contaminated Copyright: ß 2013 Fred Opperdoes. This is an open-access article distributed under the terms of the with another pancreatic hormone, the Creative Commons Attribution License, which permits unrestricted use, distribution, and in any insulin antagonist glucagon, an insight medium, provided the original author and source are credited. that led to a better understanding of the Competing Interests: The author has declared that no competing interests exist. mode of action of these two . * E-mail: [email protected]

PLOS Biology | www.plosbiology.org 1 October 2013 | Volume 11 | Issue 10 | e1001671 call ‘‘lysosome.’’ Later, together with Alex along language lines. The francophone Academy of , Arts, and Literature B. Novikoff of the Albert Einstein College part was moved 30 km south to French- of Belgium; the Pontifical Academy of of Medicine in New York, de Duve first speaking , (l’ Universite´ catholique de Sciences of the Vatican; the American saw when he made electron Louvain in Louvain-la-Neuve), and de Academy of Arts and Sciences; the micrographs of highly purified cell frac- Duve moved to Brussels with the new Academy of Sciences of ; the tions. These organelles turned out to be medical school, which was created at a Deutsche Akademie der Naturforscher loaded with hydrolytic enzymes for the separate campus from the new franco- Leopoldina; and the Royal Society of digestion of a multitude of macromole- phone university. Immediately after re- . In 1989, he was raised to the cules taken up by the cell. Thus lysosomes, ceiving the Nobel Prize, de Duve, together rank of Viscount by King Baudouin of as we now know, as the ‘‘stom- with several of his Belgian colleagues, Belgium. ach’’ of the cell’s digestive system. A few created a new biomedical institute on the In the last period of his life, this tireless years later he discovered a second - Brussels campus: the International Insti- researcher again shifted his scientific inter- elle, which was characterized by the tute of Cellular and Molecular est, this time from to the marker enzyme and was loaded (ICP), an institute of translational medi- chemical mechanisms that might have led mostly with enzymes involved in a dan- cine that was re-named the de Duve to the origin of life on Earth. A talented gerous form of oxidation, releasing toxic Institute on the occasion of his 80th writer, he wrote many influential books on peroxides, explaining why such reactions birthday in 1997. de Duve modeled the this subject as well as on biology and should be enclosed within a separate ICP after the Rockefeller University by . In total, he wrote more than a membrane-bound compartment. For this giving an absolute priority to scientific dozen books in English and in French, organelle de Duve coined the name excellence and a total freedom of research including A Guided Tour of the Living Cell; peroxisome. to its investigators. An experienced ad- Blueprint for a Cell: the and Origin of Life; The discovery of these new subcellular ministrator, he both ran the institute and Vital Dust: Life as a Cosmic Imperative; Life organelles paved the way for others to acted as fundraiser, a skill he had acquired Evolving: Molecules, , and Meaning; and identify lysosomal and peroxisomal diseas- while in the . Singularities: Landmarks on the Pathways of Life. es. Both are inherited metabolic disor- In addition to the Nobel Prize, Chris- Dr. Christian de Duve remained active ders—mutations or deletions of specific tian de Duve was the recipient of the until the very end of his life, as this genes that code for either lysosomal or Canada Gairdner International Award photograph taken in his last year demon- peroxisomal proteins, which results in a (1967), the Dr. H. P. Heineken Prize strates. He finished his last book Sept vies en dysfunctional cell organelle. (1973) from the Royal Netherlands Acad- une: Me´moires d’un Prix Nobel only a few From 1962 onwards, because of his emy of Arts and Sciences, and the E. B. months before he passed away. When he collaborative work with Claude and Pa- Wilson Award of the American Society for felt that both his health and strength were lade in New York, de Duve divided his Cell Biology (1989). In 1975, he was rapidly subsiding, he decided to end his life time between the Catholic University of elected a foreign associate of the National at the age of 95. He chose to die by an act Louvain and the Rockefeller Institute, Academy of Sciences of the United States of , while surrounded by his where he was appointed Andrew W. of America. Eighteen universities around children. Mellon professor (1962–1987). In 1968, the world awarded him honorary degrees. Christian de Duve was a brilliant Belgian politicians decided to split the He was also a member of the Royal , mentor, and writer. He will be bilingual Catholic University of Louvain Academies of Medicine and the Royal greatly missed by the scientific .

PLOS Biology | www.plosbiology.org 2 October 2013 | Volume 11 | Issue 10 | e1001671