Tuesday, May 7, 2013

Christian de Duve, Nobel Winning Biochemist


Christian de Duve, 95, Dies; Nobel-Winning Biochemist

Meyer Liebowtiz/The New York Times
Dr. Christian de Duve at the Rockefeller University in 1974.
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Dr. Christian de Duve, a Belgian biochemist whose discoveries about the internal workings of cells shed light on genetic disorders like Tay-Sachs disease and helped give birth to the field of modern cell biology, earning him a Nobel Prize, died on Saturday at his home in Nethen, Belgium. He was 95.
The cause was euthanasia, which is legal in Belgium, and which was administered by two doctors at Dr. de Duve’s request, said his son Thierry, who lives in Los Angeles.
Dr. Günter Blobel, a colleague of Dr. de Duve’s at the Rockefeller University in Manhattan, said Dr. de Duve had been “suffering from a number of health problems,” including cancer, and decided to end his life after falling a few weeks ago.
“He wanted to make the decision while he was still able to do it and not be a burden,” Dr. Blobel said.
Beginning in the late 1940s, Dr. de Duve used a centrifuge and other techniques to separate and examine the components of cells. He discovered the lysosome, a tiny sack filled with enzymes that functions like a garbage disposal, destroying bacteria or parts of the cell that are old or worn out.
His discoveries helped unravel the biology of Tay-Sachs disease and more than two dozen other genetic diseases in which a shortage of lysosomal enzymes causes waste to accumulate in cells and eventually destroy them. In Tay-Sachs, a buildup of fatty substances in the brain and other tissues leads to blindness, paralysis, mental retardation and death.
“We are sick because our cells are sick,” Dr. de Duve said.
After learning he had been awarded a Nobel, Dr. de Duve said that although his discoveries had brought great intellectual satisfaction, his goal was to use them to conquer disease. “It’s now time to give mankind some practical benefit,” he said.
Dr. de Duve shared the 1974 Nobel Prize in Physiology or Medicine with Dr. Albert Claude, who first used centrifugal techniques to glance inside cells, and Dr. George E. Palade, who pioneered using the electron microscope to better understand cell structures. Dr. Claude died in 1983; Dr. Palade died in 2008.
Before the scientists embarked on their research, the cell was perceived as a work basket containing indeterminate parts. The scientists, working separately, transformed that view with discoveries of important cell components.
Dr. Claude discovered mitochondria, which store energy, and Dr. Palade discovered ribosomes, the protein factories within cells. The Karolinska Institute, in awarding the Nobel, credited the three scientists as having founded the field of modern cell biology.
Christian René de Duve was born on Oct. 2, 1917, in Thames Ditton, England, near London. His parents were Belgians who had fled to England during World War I. When the war ended, his family returned to Belgium and settled in Antwerp. Dr. de Duve received his medical degree from the Catholic University of Louvain in 1941.
During World War II he was a medic in the Belgian Army. After German forces captured his unit in France, he managed to escape and made his way back to Belgium.
Dr. de Duve soon resumed his medical training at the Catholic University of Louvain’s Cancer Institute while pursuing graduate studies in chemistry. He wrote a book on insulin, the subject of his thesis. He received his doctorate in chemistry in 1945.
Intent on a career in research, he set off for labs in Sweden and the United States to study biochemistry. Over the next two years, he studied under Hugo Theorell at the Medical Nobel Institute in Stockholm and Carl Cori and Gerty Cori at Washington University in St. Louis, all of whom would later receive Nobel Prizes. Dr. de Duve returned to the Catholic University of Louvain in 1947 to teach physiological chemistry. He became a full professor in 1951.
His research continued to focus on insulin, a hormone involved in the regulation of blood sugar. Working with liver cells, he used Dr. Claude’s recently developed centrifugal techniques to separate cell parts. Centrifuges are spinning devices that speed up the rate at which particles settle in liquid. Dr. Claude’s technique called for using a pestle to break open cells before placing them in the centrifuge.
In one experiment, Dr. de Duve noticed that acid phosphatase, an enzyme he had included as a control, was less active than in earlier experiments in which he had used an electric blender instead of a pestle to break up cells. He was intrigued and pursued his chance finding.
“My curiosity got the better of me,” he wrote in his Nobel autobiography, “and as a result, I never elucidated the mechanism of action of insulin.”
In further experiments, Dr. de Duve found that the enzyme was contained in some sort of membrane; cells broken up in the blender released more of the enzyme because the membrane suffered greater damage. Because the enzyme was so acidic, he concluded that its only purpose could be digestion. He called the membrane lysosome, and later identified it in pictures taken with an electron microscope.
After the discovery, other researchers went on to identify more than 50 lysosomal enzymes and some genetic diseases that result when an enzyme either is absent or does not function properly. Today, some of these conditions, like Pompe disease, which causes sugar to accumulate in the liver and other organs, are treated with drugs that supply the needed enzyme. Other illnesses, like Tay-Sachs disease, have no effective treatments.
Dr. de Duve became a professor at the Rockefeller University in 1962 and began splitting his time between his laboratories there and at Louvain. In 1974, he founded the International Institute of Cellular and Molecular Pathology in Brussels.
He became emeritus professor at the Catholic University of Louvain in 1985 and at Rockefeller in 1988. He retired as president of the pathology institute in 1991.
In his later years he applied his knowledge of biochemistry to the study of the origins of life. He wrote several books, including “A Guided Tour of the Living Cell” (1984), and “Genetics of Original Sin: The Impact of Natural Selection on the Future of Humanity” (2012).
Besides his son Thierry, survivors include another son, Alain; two daughters, Anne and Françoise; two brothers, Pierre and Daniel; seven grandchildren; and two great-grandsons.
Dr. de Duve spent his last month writing letters telling friends and colleagues of his decision to end his life. In an interview with the Belgian newspaper Le Soir, published after his death, he said he had put off his death until his four children could be with him.
In the interview, he said he was at peace with his decision.
“It would be an exaggeration to say I’m not afraid of death,” he said, “but I’m not afraid of what comes after, because I’m not a believer.”

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