Christian de Duvé Biography (1917-)

biochemist, cell biologist

Christian René de Duvé's ground-breaking studies of cellular structure and function earned him the 1974 Nobel Prize in physiology or medicine (shared with Albert Claude and George Palade ). His discovery of the two key cellular organelles--lysosomes and peroxisomes--earned him an honor from the Swedish Academy. This work, along with that of his fellow recipients, established the field of cell biology. De Duvé introduced techniques that have enabled other scientists to better study cellular anatomy and physiologyand his research has also been of great value in helping clarify the causes of and treatments for a number of diseases.

Christian René de Duvé was born on October 2, 1917 in England after his parents, Alphonse and Madeleine (Pungs) de Duvé, fled Belgiumafter the German army invaded it during World War I. De Duvé returnedwith his parents to Belgium in 1920, where they settled in Antwerp. (De Duvé later became a Belgian citizen.) In 1934, intending to become a physician, de Duvé entered the medical school of the Catholic University ofLouvain.

De Duvé joined J. P. Bouckaert's group, where he studied physiology, concentrating on the hormone insulin and its effects on uptake of the sugar glucose. De Duvé's experiences in Bouckaert's laboratory convinced him to pursue a research career when he graduated with an M.D. in 1941. During World War II De Duvé spent time in a prison camp, but managed to escape and returned to Louvain to resume his investigations of insulin. Before obtaining his Ph.D. from the Catholic University of Louvain in 1945, de Duvépublished several works, including a 400-page book on glucose, insulin, anddiabetes. The dissertation topic for his Agrégé de l'Enseignement Supérieur was also insulin. De Duvé then obtained anM.Sc. degree in chemistry in 1946.

After graduation, de Duvé studied with Hugo Theorell at the Medical Nobel Institute in Stockholm for 18 months, then spent six months with Carl Ferdinand Cori, Gerty Cori, and Earl Sutherland at Washington University Schoolof Medicine in St. Louis. Thus, in his early postdoctoral years he worked closely with no less than four future Nobel Prize winners. De Duvé returned to Louvain in 1947 to take up a faculty post at his alma mater teaching physiological chemistry at the medical school. In 1951, de Duvé was appointed full professor of biochemistry. As he began his faculty career, de Duvé's research was targeted at unraveling the mechanism of action of theanti-diabetic hormone, insulin and his early experiments opened new avenues of research.

As a consequence of investigating how insulin works in the human body, de Duvé and his students also studied the enzymes involved in carbohydrate metabolism in the liver. Duvé separated liver cell components by spinning them in a centrifuge, a machine that rotates at high speed. De Duvéassumed that particular enzymes are associated with particular parts of thecell. These parts, called cellular organelles (little organs) can be seen inthe microscope as variously shaped and sized grains and particles within thebody of cells. It had long been recognized that there existed several discrete types of these organelles, though little was known about their structures or functions at the time.

Using a technique called differential centrifugation, developed some years earlier by fellow-Belgian Albert Claude at the Rockefeller Institute for Medical Research, in which cells are ground up slightly by hand prior to being spunto separate various components, de Duvé got better separation of liver cell organelles, and was able to isolate certain enzymes to certain cell fractions. One of his first findings was that his target enzyme, glucose-6-phosphatase, associated with the cellular organelles, microsomes, were the site of key cellular metabolic events. This was the first time a particular enzymehad been clearly associated with a particular organelle.

De Duvé and his students also applied the differential centrifugationtechnique to the enzyme acid phosphatase, which in cells acts to remove phosphate groups from sugar molecules under acidic conditions. He and his studentsobserved that the cell fraction initially showed a lower level of enzyme than expected, but when allowed to sit in the refrigerator for several days, theenzyme activity increased to expected levels. This phenomenon became known as enzyme latency.

De Duvé found an organelle devoted to cellular digestion. With this research, de Duvé identified lysosomes and elucidated their pivotal rolein cellular digestive and metabolic processes. Later research in de Duvé's laboratory showed that lysosomes play critical roles in a number of disease processes as well.

De Duvé eventually uncovered more associations between enzymes and organelles. His research on monoamine oxidase showed that the enzyme was associated with a separate cellular organelle, the peroxisome. Further investigationled to more discoveries about this previously unknown organelle. It was discovered that peroxisomes contain enzymes that use oxygen to break up certain types of molecules. They are vital to neutralizing many toxic substances, suchas alcohol, and play key roles in sugar metabolism.

Using the technique that he had used in these early experiments, de Duvé pioneered its use to answer questions of both basic biological interest and immense medical application. His group discovered that certain diseases result from cells' inability to properly digest their own waste products. Disorders of glycogen storage, including Tay Sachs disease, result from malfunctioning lysosomal enzymes.

In 1962 de Duvé joined the Rockefeller Institute (now Rockefeller University) while keeping his appointment at Louvain. Working with research groups at both institutions, he has studied inflammatory diseases such as arthritis and arteriosclerosis, genetic diseases, immune dysfunctions, tropical maladies, and cancers, leading to the creation of new drugs used in combatting some of these conditions. In 1971 de Duvé formed the International Institute of Cellular and Molecular Pathology, affiliated with the University at Louvain. Research at the institute focuses on incorporating the findings from basic cellular research into practical applications.

De Duvé helped found the American Society for Cell Biology. He has received awards and honors from many countries, including more than a dozen honorary degrees. In 1974, de Duvé, along with Albert Claude and George Palade, both also of the Rockefeller Institute, received the Nobel Prize in physiology or medicine, and were credited with creating the discipline of scientific investigation that became known as cell biology. De Duvé was elected a foreign associate of the United States National Academy of Sciences in1975, and has been acclaimed by Belgian, French, and British biochemical societies. He has also served as a member of numerous prestigious biomedical andhealth-related organizations around the globe.

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