de Duvé, Christian (René Marie Joseph) 1917-

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de DUVÉ, Christian (René Marie Joseph) 1917-

PERSONAL: Born October 2, 1917, in Thames-Ditton, England; immigrated to Belgium, 1920; naturalized Belgian citizen; son of Alphonse and Madeleine (Pungs) de Duvé; married Janine Herman, September 30, 1943; children: Thierry, Anne, Françoise, Alain. Education: Catholic University of Louvain, M.D., 1941, Ph.D., 1945, M.Sc., 1946; additional study at the Medical Nobel Institute, Stockholm, Sweden, and Washington University, St. Louis, MO.

ADDRESSES: Office—c/o Christian de Duvé Institute of Cellular Pathology, 75 ave. Hippocrate, B-1200 Brussels, Belgium.

CAREER: Biochemist and cell biologist. Catholic University of Louvain, Louvain, Belgium, instructor in physiological chemistry, 1947-51, professor of biochemistry, 1951-85, professor emeritus, 1985—. Rockefeller University, affiliate, 1962-64, professor, 1964-74, Andrew W. Mellon Professor, 1974-88, professor emeritus, 1988—. Mayne Guest Professor, University of Queensland, 1972; visiting professor at Albert Einstein College of Medicine, 1961-62, State University of Ghent, 1962-63, Free University of Brussels, 1963-64, State University of Liege, 1972-73, Universitaires Notre-Dame de la Paix, Namur, 1990-91. International Institute of Cellular and Molecular Pathology, founder, 1971, president, 1974-91; Christian de Duvé Institute of Cellular Pathology, affiliate; advisor to numerous agencies and organizations, including Ciba Foundation, National Institute for Child Health of National Institute of Health, World Health Organization, Max Planck-Institute for Immunobiology, Ludwig Institute for Cancer Research, Mary Imogene Bassett Research Institute, Clinical Research Institute of Montreal, and Basel Institute for Immunology.

MEMBER: International Society for Cell Biology, European Association for the Study of Diabetes, European Molecular Biology Organization, European Cell Biology Organization, Academia Europaea (foreign associate), American Society for Cell Biology (founding member; member of council, 1966-69), American Society of Biological Chemists, American Chemical Society, American Association for the Advancement of Science (fellow), National Academy of Sciences (United States; foreign associate, 1975), American Philosophical Society, American Academy of Arts and Sciences (foreign associate), Biochemical Society, Royal Academy of Belgium, Societe Belge Biochim. (president, 1962-64), Societe Belge de Physiologie, Koninklyke Akademie voor Geneeskunde, Royal Academy of Medicine, Royal Academy (London, England; foreign associate), Royal Society of Canada (foreign associate), Société Chimie Biologique, Académie des Sciences de Paris (foreign associate), Deutsche Akademie der Naturforscher Leopoldina, Deutsche Gesellschaft für Zellbiologie (foreign associate), Athenian Academy of Sciences (foreign associate), Pontifical Academy of Science, New York Academy of Sciences, Sigma Xi.

AWARDS, HONORS: Therese and Johan Anderson Stiftelse fellow in Stockholm, Sweden, 1946-47; Rockefeller Foundation fellow, 1947-48; Prix Pfizer, Royal Academy of Medicine (Belgium), 1957; Prix Francqui, 1960; Prix Quinquennal Belge des Sciences Medicales, Government of Belgium, 1967; award of merit, Gairdner Foundation International, 1967; Dr. H. P. Heineken Prize, Royal Netherlands Academy of Science, 1973; Nobel Prize in medicine (with Albert Claude and George Palade), 1974; Harden Award, Biochemical Society (England), 1978; Theobald Smith Award, Albany Medical College, 1981; Jimenez Diaz Award, 1985; E. B. Wilson Award, American Society for Cell Biology, 1989; numerous honorary degrees, including ones from University of Turin, University of Leiden, University of Lille, Gustavus Adolphus College, University of Keele, University of Montreal, and Rockefeller University; various awards from Belgian, French, and British biochemical societies.

WRITINGS:

Glucose, insuline, et diabéte, [Paris, France], 1945.

A Guided Tour of the Living Cell, two volumes, Scientific American Library (New York, NY), 1985.

Blueprint for a Cell: The Nature and Origin of Life, N. Patterson (Burlington, NC), 1991.

Vital Dust: Life As a Cosmic Imperative, Basic Books (New York, NY), 1995.

Life Evolving: Molecules, Mind, and Meaning, Oxford University Press (New York, NY), 2002.

À l'écoute du vivant, Odile Jacob (Paris, France), 2002.

Contributor of articles and reviews to periodicals, including American Scientist, International Review of Cytology, Proceedings of the Royal Society, Journal of Cell Biology, and Scientific American. Member of editorial board, Subcellular Biochemistry, 1971-87, Preparative Biochemistry, 1971-80, and Molecular and Cellular Biochemistry, 1973-80.

SIDELIGHTS: Christian de Duvé's ground-breaking studies of cellular structure and function earned him a Nobel Prize in 1974. However, he did much more than discover the two key cellular organelles—lysosomes and peroxisomes—for which the Swedish Academy honored him. His work, along with that of his fellow recipients, established an entirely new field, that of cell biology. De Duvé introduced techniques that have enabled other scientists to better study cellular anatomy and physiology. De Duvé's research has also been of great value in helping clarify the causes of and treatments for a number of diseases.

De Duvé's parents had fled Belgium after its invasion by the German Army in World War I, escaping to safety in England. There, in Thames-Ditton, Christian de Duvé was born. He returned with his parents to Belgium in 1920, and they settled in Antwerp. As a child, de Duvé journeyed throughout Europe, picking up three foreign languages in the process, and in 1934 enrolled in the Catholic University of Louvain, where he received an education in the "ancient humanities." Deciding to become a physician, he entered the medical school of the university.

Finding the pace of medical training relaxed, and realizing that the better students gravitated to research labs, de Duvé joined a group headed by J. P. Bouckaert. Here 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. World War II disrupted his plans, and de Duvé ended up in a prison camp. He managed to escape and subsequently returned to Louvain to resume his investigations of insulin. Although his access to experimental supplies and equipment was limited, he was able to read extensively from the early literature on the subject. Even before obtaining his Ph.D. from the Catholic University of Louvain in 1945, de Duvé had published several works, including a 400-page book on glucose, insulin, and diabetes. De Duvé then obtained an M.Sc. degree in chemistry in 1946.

After graduation, de Duvé decided that he needed a thorough grounding in biochemical approaches to pursue his research interests. He studied with Hugo Theorell at the Medical Nobel Institute in Stockholm for eighteen months, then spent six months with Carl Ferdinand Cori, Gerty Cori, and Earl Sutherland at Washington University School of Medicine in St. Louis. Thus, in his early postdoctoral years he worked closely with no less than four future Nobel Prize winners. It is not surprising that, after this hectic period, de Duvé was happy to return 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 still targeted at unraveling the mechanism of action of the anti-diabetic hormone, insulin. While he was not successful at his primary effort (indeed the answer to de Duvé's first research question was to elude investigators for more than thirty years), 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. It was these studies that proved pivotal for de Duvé's eventual rise to scientific fame. In his first efforts, he had tried to purify a particular liver enzyme, glucose-6-phosphatase, that he believed blocked the effect of insulin on liver cells. Many enzymes would solidify and precipitate out of solution when exposed to an electric field. Most could then be redissolved in a relatively pure form given the right set of conditions, but glucose-6-phosphate stubbornly remained a solid precipitate. The failure of this electrical separation method led de Duvé to try a different technique, separating components of the cell by spinning them in a centrifuge, a machine that rotates at high speed. De Duvé assumed that particular enzymes are associated with particular parts of the cell. These parts, called cellular organelles (little organs) can be seen in the microscope as variously shaped and sized grains and particles within the body 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.

The basic principles of centrifugation for separating cell parts had been known for many years. First cells are ground up (homogenized) and the resultant slurry placed in a narrow tube. The tube is placed in a centrifuge, and the artificial gravity that is set up by rotation will separate material by weight. Heavier fragments and particles will be driven to the bottom of the tube while lighter materials will layer out on top. At the time de Duvé began his work, centrifugation could be used to gather roughly four different fractions of cellular debris. This division proved to be too crude for his research, because he needed to separate out various cellular organelles more selectively.

For this reason, de Duvé turned to a technique developed some years earlier by fellow-Belgian Albert Claude while working at the Rockefeller Institute for Medical Research. In the more common centrifugation technique, the cells of interest were first vigorously homogenized in a blender before being centrifuged. In Claude's technique of differential centrifugation, however, cells were treated much more gently, being merely ground up slightly by hand prior to being spun to separate various components.

When de Duvé used this differential centrifugal fractionation technique on liver cells, he did indeed get better separation of 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, was associated with microsomes, cellular organelles which had been, until that time, considered by cell biologists to be quite uninteresting. De Duvé's work showed that they were the site of key cellular metabolic events. Further, this was the first time a particular enzyme had been clearly associated with a particular organelle.

De Duvé was also studying an enzyme called acid phosphatase that acts in cells to remove phosphate groups (chemical clusters made up of one phosphorus and three oxygen atoms) from sugar molecules under acidic conditions. The differential centrifugation technique isolated acid phosphatase to a particular cellular fraction, but measurements of enzyme activity showed much lower levels than expected. De Duvé was puzzled. What had happened to the enzyme? He and his students observed that if the cell fraction that initially showed this low level of enzyme were allowed to sit in the refrigerator for several days, the enzyme activity increased to expected levels. This phenomenon became known as enzyme latency.

De Duvé believed he had a solution to the latency mystery. He reasoned that perhaps the early, gentle hand-grinding of differential centrifugation did not damage the cellular organelles as much as did the more traditional mechanical grinding. What if, he wondered, some enzymes were not freely exposed in the cells' interiors, but instead were enclosed within protective membranes of organelles. If these organelles were not then broken apart by the gentle grinding, the enzyme might still lie trapped within the organelles in the particular cell fraction after centrifugation. If so, it would be isolated from the chemicals used to measure enzyme activity. This would explain the low initial enzyme activity, and why over time, as the organelles' membranes gradually deteriorated, enzyme activity would increase.

De Duvé realized that his ideas had powerful implications for cellular research. By carefully observing what enzymes were expressed in what fractions and under what conditions, de Duvé's students were able to separate various enzymes and associate them with particular cellular organelles. By performing successive grinding and fractionations, and by using compounds such as detergents to break up membranes, de Duvé's group began making sense out of the complex world that exists within cells.

De Duvé's research built on the work of other scientists. Previous research had clarified some of the roles of various enzymes. But de Duvé came to realize that there existed a group of several enzymes, in addition to acid phosphatase, whose primary functions all related to breaking down certain classes of molecules. These enzymes were always expressed in the same cellular fraction and showed the same latency. Putting this information together, de Duvé realized that he had found an organelle devoted to cellular digestion. It made sense, he reasoned, that these enzymes should be sequestered away from other cell components. They functioned best in a different environment, expressing their activity fully only under acidic conditions (the main cell interior is neutral). Moreover, these enzymes could damage many other cellular components if set loose in the interiors of the cells. With this research, de Duvé identified lysosomes and elucidated their pivotal role in 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. The enzyme monoamine oxidase, for example, behaved very similarly to the enzymes of the lysosome, but de Duvé's careful and meticulous investigations revealed minor differences in when and where it appeared. He eventually showed that monoamine oxidase was associated with a separate cellular organelle, the peroxisome. Further investigation led 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, such as alcohol, and play key roles in sugar metabolism.

Recognizing the power of 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 the inability of cells to properly digest their own waste products. For example, a group of illnesses known collectively as disorders of glycogen storage result from malfunctioning lysosomal enzymes. Tay Sachs disease, a congenital neurological disorder that kills its victims by age five, results from the accumulation of a component of the cell membrane that is not adequately metabolized due to a defective lysosomal enzyme.

In 1962 de Duvé joined the Rockefeller Institute (now Rockefeller University) while keeping his appointment at Louvain. In subsequent years, working with numerous research groups at both institutions, he studied inflammatory diseases such as arthritis and arteriosclerosis, genetic diseases, immune dysfunctions, tropical maladies, and cancers. This work has led, in some cases, 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's work has won him the respect of his colleagues. Workers throughout the broad field of cellular biology recognize their debt to his pioneering studies. He 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 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 U.S. National Academy of Sciences in 1975, and has been acclaimed by Belgian, French, and British biochemical societies. He has also served as a member of numerous prestigious biomedical and health-related organizations around the globe.