Christian de Duve

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Christian de Duve

Viscount de Duve
eukaryotic cell in 2012
Born
Christian René Marie Joseph de Duve

(1917-10-02)2 October 1917
Thames Ditton, Surrey, England
Died4 May 2013(2013-05-04) (aged 95)
, Belgium
NationalityBelgian
Alma mater
Known for
Cell organelles
Children4, including Thierry
Awards
See list
Scientific career
Fields
Institutions

Christian René Marie Joseph, Viscount de Duve (2 October 1917 – 4 May 2013) was a Nobel Prize-winning Belgian

George E. Palade ("for their discoveries concerning the structural and functional organization of the cell").[3] In addition to peroxisome and lysosome, he invented scientific names such as autophagy, endocytosis, and exocytosis in a single occasion.[4][5][6][7][8]

The son of Belgian refugees during the

diabetes mellitus. His thesis earned him the highest university degree agrégation de l'enseignement supérieur (equivalent to PhD) in 1945.[10]

With his work on the purification of

University of Louvain in 1985, and of Rockefeller in 1988.[12]

De Duve was granted the rank of

L'Oréal-UNESCO Awards for Women in Science.[13] He died by legal euthanasia after long suffering from cancer and atrial fibrillation.[14][15]

Early life and education

De Duve was born of an estate agent Alphonse de Duve and wife Madeleine Pungs in the village of Thames Ditton, near London. His parents fled Belgium at the outbreak of the First World War. After the war in 1920, at age three, he and his family returned to Belgium. He was a precocious boy, always the best student (primus perpetuus as he recalled) in school, except for one year when he was pronounced "out of competition" to give chance to other students.[2]

He was educated by the

Onze-Lieve-Vrouwinstituut in Antwerp, before studying at the Catholic University of Leuven in 1934.[16] He wanted to specialize in endocrinology and joined the laboratory of the Belgian physiologist Joseph P. Bouckaert, whose primary interest was one insulin.[17] During his last year at medical school in 1940, the Germans invaded Belgium. He was drafted to the Belgian army, and posted in southern France as medical officer. There, he was almost immediately taken as prisoner of war by Germans. His ability to speak fluent German and Flemish helped him outwit his captors. He escaped back to Belgium in an adventure he later described as "more comical than heroic".[10]

He immediately continued his medical course, and obtained his

pancreatic hormone, the insulin antagonist glucagon.[17] However, laboratory supplies at Leuven were in shortage, therefore he enrolled in a programme to earn a degree in chemistry at the Cancer Institute. His research on insulin was summed up in a 400-page book titled Glucose, Insuline et Diabète (Glucose, Insulin and Diabetes) published in 1945, simultaneously in Brussels and Paris. The book was condensed into a technical dissertation which earned him the most advanced degree at the university level agrégation de l'enseignement supérieur (an equivalent of a doctorate – he called it "a sort of glorified PhD") in 1945.[10] His thesis was followed by a number of scientific publications.[18] He subsequently obtained a MSc in chemistry in 1946, for which he worked on the purification of penicillin.[19]

To enhance his skill in biochemistry, he trained in the laboratory of

Gerti Cori at Washington University in St. Louis (the husband and wife were joint winners of The Nobel Prize in Physiology or Medicine in 1947).[20]

Career and research

In March 1947 de Duve joined the faculty of the medical school of the Catholic University of Leuven teaching physiological chemistry. In 1951 he became full professor. In 1960, Detlev Bronk, the then president of the Rockfeller Institute (what is now Rockefeller University) of New York City, met him at Brussels and offered him professorship and a laboratory. The rector of Leuven, afraid of entirely losing de Duve, made a compromise over dinner that de Duve would still be under part-time appointment with a relief from teaching and conducting examinations. The rector and Bronk made an agreement which would initially last for five years. The official implementation was in 1962, and de Duve simultaneously headed the research laboratories at Leuven and at Rockefeller University, dividing his time between New York and Leuven.[21]

In 1969, the Catholic University of Leuven was contentiously

Rediscovery of glucagon

The hormone

Earl Wilbur Sutherland, Jr., who later won the Nobel Prize in Physiology or Medicine in 1971.[17]

Sutherland had been working on the puzzle of the insulin-impurity substance, which he had named hyperglycemic-glycogenolytic (HG) factor. He and de Duve soon discovered that the HG factor was synthesised not only by the pancreas but also by the

alpha cells. It was de Duve who realised that Sutherland's HG factor was in fact the same as glucagon; this rediscovery led to its permanent name, which de Duve reintroduced it in 1951. The pair's work showed that glucagon was the major hormone influencing the breakdown of glycogen in the liver—the process known as glycogenolysis—by which more sugars are produced and released into the blood.[38]

De Duve's original hypothesis that glucagon was produced by pancreatic alpha cells was proven correct when he demonstrated that selectively

guinea pigs;[39] he finally isolated the purified hormone in 1953,[40] including those from birds.[41][42][43][44]

De Duve was first to hypothesise that the production of insulin (which decreased blood sugar levels), stimulated the uptake of glucose in the liver; he also proposed that a mechanism was in-place to balance the productions of insulin and glucagon in order to maintain normal blood sugar level, (see homeostasis). This idea was much disputed at the time, but his rediscovery of glucagon confirmed his theses. In 1953 he experimentally demonstrated that glucagon did influence the production (and thus the uptake) of glucose.[45][46]

Discovery of lysosome

Christian de Duve and his team continued studying the insulin mechanism-of-action in liver cells, focusing on the enzyme

blood sugar levels,[47][48] but, they could not, even after repeated experiments, purify and isolate the enzyme from the cellular extracts. So they tried the more laborious procedure of cell fractionation to detect the enzyme activity.[49]

This was the moment of serendipitous discovery. To estimate the exact enzyme activity, the team adopted a procedure using a standardised enzyme acid phosphatase; but they were finding the activity was unexpectedly low—quite low, i.e., some 10% of the expected value. Then one day they measured the enzyme activity of some purified cell fractions that had been stored for five days. To their surprise the enzyme activity was increased back to that of the fresh sample; and similar results were replicated every time the procedure was repeated. This led to the hypothesis that some sort of barrier restricted rapid access of the enzyme to its substrate, so that the enzymes were able to diffuse only after a period of time. They described the barrier as membrane-like—a "saclike structure surrounded by a membrane and containing acid phosphatase."[50][51]

An unrelated enzyme (of the cell fractionation procedure) had come from membranous fractions that were known to be cell organelles. In 1955, de Duve named them "lysosomes" to reflect their digestive properties.

acid hydrolases) of lysosomes.[23][53]

Discovery of peroxisome

Serendipity followed de Duve for another major discovery. After the confirmation of lysosome, de Duve's team was troubled by the presence (in the rat liver cell fraction) of the enzyme urate oxidase. De Duve thought it was not a lysosome because it is not an acid hydrolase, typical of lysosomal enzymes; still, it had similar distribution as the enzyme acid phosphatase. Further, in 1960 he found other enzymes (such as catalase and D-amino acid oxidase), that were similarly distributed in the cell fraction—and it was then thought that these were mitochondrial enzymes.[54] (W. Bernhard and C. Rouillier had described such extra-mitochondrial organelles as microbodies, and believed that they were precursors to mitochondria.)[55] de Duve noted the three enzymes exhibited similar chemical properties and were similar to those of other peroxide-producing oxidases.[56]

De Duve was skeptical of referring to the new-found enzymes as microbodies because, as he noted, "too little is known of their enzyme complement and of their role in the physiology of the liver cells to substantiate a proposal at the present time".[57] He suggested that these enzymes belonged to the same cell organelle, but one different from previously known organelles.[23] But, as strong evidences were still lacking, he did not publish his hypothesis. In 1955 his team demonstrated similar cell fractions with same biochemical properties from the ciliated protozoan Tetrahymena pyriformis; thus, it was indicated that the particles were undescribed cell organelles unrelated to mitochondria. He presented his discovery at a meeting of the American Society for Cell Biology in 1955,[58] and formally published in 1966, creating the name peroxisomes for the organelles as they are involved in peroxidase reactions.[59] In 1968 he achieved the first large-scale preparation of peroxisomes, confirming that l-α hydroxyacid oxidase, d-amino acid oxidase, and catalase were all the unique enzymes of peroxisomes.[60][61]

De Duve and his team went on to show that peroxisomes play important metabolic roles, including the

glyoxysomes and glycosomes.)[17][62][63]

Origin of cells

De Duve's work has contributed to the emerging consensus towards accepting the

endosymbionts. According to de Duve's version, eukaryotic cells with their structures and properties, including their ability to capture food by endocytosis and digest it intracellularly, developed first. Later, prokaryotic cells were incorporated to form more organelles.[64]

De Duve proposed that peroxisomes, which allowed cells to withstand the growing amounts of free molecular oxygen in the early-Earth atmosphere, may have been the first endosymbionts. Because peroxisomes have no

origin of life studies, which he admitted was still a speculative field (see thioester).[67][68]

Publications

De Duve was a prolific writer, both in technical and popular works. The most notable works are:

Personal life

Religious beliefs

De Duve was brought up as a

Roman Catholic. In his later years he tended towards agnosticism, if not strict atheism.[69][70] However, de Duve believed that "Most biologists, today, tend to see life and mind as cosmic imperatives, written into the very fabric of the universe, rather than as extraordinarily improbable products of chance."[71] "It would be an exaggeration to say I'm not afraid of death", he explicitly said to a Belgian newspaper Le Soir just a month before his death, "but I'm not afraid of what comes after, because I'm not a believer."[72][73]

He strongly supported

biological evolution as a fact, and dismissive of creation science and intelligent design, as explicitly stated in his last book, Genetics of Original Sin: The Impact of Natural Selection on the Future of Humanity. He was among the seventy-eight Nobel laureates in science to endorse the effort to repeal the Louisiana Science Education Act of 2008.[74]

Family

His family (von Duve) came from Hanover and settled in Belgium after the Battle of Waterloo.
De Duve married Janine Herman on 30 September 1943. Together they had had two sons, one of whom is noted art professor Thierry de Duve, and two daughters.

Janine died in 2008, aged 86.[19]

Death

De Duve died on 4 May 2013, at his home in Nethen, Belgium, aged 95. He decided to end his life by legal euthanasia, performed by two doctors and in the presence of his four children. He had been long suffering from cancer and atrial fibrillation, and his health problems were exacerbated by a recent fall in his home.[75][14][15][76]

De Duve was cremated as he had willed, and his ashes were distributed among family members and friends.

Awards and honours

Dutch Queen Beatrix meets 5 Nobel Prize winners: Paul Berg, Christian de Duve, Steven Weinberg, Manfred Eigen, Nicolaas Bloembergen (1983)

De Duve won the

Dr H.P. Heineken Prize for Biochemistry and Biophysics in 1973 from the Royal Netherlands Academy of Arts and Sciences.[79]

He was elected a foreign associate of the

He was also a member of the Royal Academies of Medicine and the

honorary doctorates from eighteen universities around the world.[20]

Legacy

De Duve founded a multidisciplinary biomedical research institute at Université catholique de Louvain in 1974, originally named the International Institute of Cellular and Molecular Pathology (ICP).[83] He remained its president until 1991. On his 80th birthday in 1997 it was renamed the Christian de Duve Institute of Cellular Pathology. In 2005 its name was further contracted to simply the de Duve Institute.[84]

De Duve was one of the founding members of the Belgian Society of Biochemistry and Molecular Biology, established on 15 September 1951.[85]

De Duve is remembered as an inventor of important scientific terminology. He coined the word lysosome in 1955, peroxisome in 1966, and autophagy, endocytosis, and exocytosis in one instance at the Ciba Foundation Symposium on Lysosomes held in London during 12–14 February 1963, while he, "was in a word-coining mood."[23][86]

De Duve's life, including his work resulting in a Nobel Prize, and his passion for biology is the subject of a documentary film Portrait of a Nobel Prize: Christian de Duve (Portrait de Nobel : Christian de Duve), directed by Aurélie Wijnants. It was first aired on Eurochannel in 2012.[87]

References

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External links