Christian de Duve
|Christian de Duve|
de Duve lecturing on the origin of the eukaryotic cell in October 2012
Christian René Marie Joseph de Duve|
2 October 1917
Thames Ditton, Surrey, UK
4 May 2013 95) (aged|
|Known for||Cell organelles|
(m. 1943; d. 2008)
Christian René Marie Joseph, Viscount de Duve (2 October 1917 – 4 May 2013) was a Nobel Prize-winning Belgian cytologist and biochemist. He made serendipitous discoveries of two cell organelles, peroxisome and lysosome, for which he shared the Nobel Prize in Physiology or Medicine in 1974 with Albert Claude and George E. Palade ("for their discoveries concerning the structural and functional organization of the cell"). In addition to peroxisome and lysosome, he invented the scientific names such as autophagy, endocytosis, and exocytosis in a single occasion.
His family returned to Belgium in 1920. He was educated by the Jesuits at Onze-Lieve-Vrouwinstituut in Antwerp, and studied medicine at the Catholic University of Leuven. Upon earning his MD in 1941, he joined research in chemistry, working on insulin and its role in diabetes mellitus. His thesis earned him the highest university degree agrégation de l'enseignement supérieur (equivalent to PhD) in 1945.
With his work on the purification of penicillin, he obtained an MSc degree in 1946. He went for further training under (later Nobel Prize winners) Hugo Theorell at the Karolinska Institutet in Stockholm, and Carl and Gerti Cori at the Washington University in St. Louis. He joined the faculty of medicine at Leuven in 1947. In 1960 he was invited to the Rockfeller Institute (now Rockefeller University). With mutual arrangement with Leuven, he became professor in both universities from 1962, dividing his time between Leuven and New York. He became emeritus professor of Leuven university in 1985, and of Rockefeller in 1988.
De Duve was granted the rank of Viscount in 1989 by King Baudouin of Belgium. He was also a recipient of Francqui Prize, Gairdner Foundation International Award, Heineken Prize, and E. B. Wilson Medal. In 1974 he founded the International Institute of Cellular and Molecular Pathology in Brussels, eventually renamed the de Duve Institute in 2005. He was the founding President of the L'Oréal-UNESCO Awards for Women in Science.
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.
He was educated by the Jesuits at Onze-Lieve-Vrouwinstituut in Antwerp, before studying at the Catholic University of Leuven in 1934. He wanted to specialize in endocrinology and joined the laboratory of the Belgian physiologist Joseph P. Bouckaert.
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".
He immediately continued his medical course, and obtained his MD in 1941 from Leuven. After graduation, de Duve's primary research was on insulin and its role in glucose metabolism. He made an initial discovery that a commercial preparation of insulin was contaminated with another pancreatic hormone, the insulin antagonist glucagon.
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 Ph.D.") in 1945. His thesis was followed by a number of scientific publications.
To enhance his skill in biochemistry, he trained in the laboratory of Hugo Theorell (who later won The Nobel Prize in Physiology or Medicine in 1955) at the Nobel Medical Institute in Stockholm for 18 months during 1946-47. In 1947, he received a financial assistance as Rockefeller Foundation fellow and worked for six months with Carl and 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).
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.
In 1969, the Leuven university was split into two separate universities. He joined the French-speaking side of Université catholique de Louvain. He took emeritus status at Université catholique de Louvain in 1985 and at Rockefeller in 1988, though he continued to conduct research. Among other subjects, he studied the distribution of enzymes in rat liver cells using rate-zonal centrifugation. His work on cell fractionation provided an insight into the function of cell structures. He specialized in subcellular biochemistry and cell biology and discovered new cell organelles.
Rediscovery of glucagon
Its true biological importance was not known and the name itself was ignored. At the time de Duve joined Bouckaert at Leuven university to work on insulin, it still remained a mystery. Insulin was the first commercial hormonal drug originally produced by the Eli Lilly and Company since 1921, but their extraction suffered from impurity which caused mild hyperglycaemia, the very opposite of what they expected. In May 1944 de Duve realised that the insulin impurity could be removed by crystallisation. He demonstrated that the insulin produced of ELi Lilly was contaminated by the impurity, whereas that of the Danish Novo was not. The Eli Lilly insulin caused initial hyperglycaemia, and the Novo insulin did not when he injected them into rats. His experiments were published in 1947, following which the Eli Lilly upgraded its method to produce purified insulin. By then he had joined Carl and Gerti Cori's at Washington University in St. Louis, where he worked with a fellow researcher Earl Wilbur Sutherland, Jr. (who later won the Nobel Prize in Physiology or Medicine in 1971).
Sutherland had been working on the insulin-impurity substance and had named it hyperglycemic-glycogenolytic (HG) factor. He and de Duve immediately discovered that the HG factor was synthesised not only by the pancreas but, surprisingly, by the gastric mucosa and certain other parts of the digestive tract. They further found that the hormone was produced from pancreatic islets by cells differing from the insulin-producing beta cells, presumably the alpha cells. It was de Duve who realised that Sutherland's HG factor was glucagon, and this rediscovery led to its permanent name, which he reintroduced it in 1951. They showed that glucagon was the major hormone influencing the breakdown of glycogen (glycogenolysis) in the liver, by which more sugars are produced in the blood.
De Duve's original hypothesis that glucagon was produced by pancreatic alpha cells was proved right when it was demonstrated that selectively cobalt-damage alpha cells stopped producing glucagon in guinea pigs, and finally isolated the purified hormone in 1953, including those from birds.
De Duve was the first to hypothesise that production of insulin to decrease blood sugar level stimulated the uptake of glucose in the liver, and that there is a balanced production of insulin and glucagon to maintain normal blood sugar level. His idea was ridiculed at the time. But his rediscovery of glucagon confirmed his ideas. In 1953 he experimentally demonstrated that glucagon did influence the production and thus uptake of glucose.
Discovery of lysosome
Christian de Duve continued his research on insulin mechanism of action in liver cells. He and his team focused on the enzyme glucose 6-phosphatase, which is the key enzyme in sugar metabolism (glycolysis) and the target of insulin. They found out that it was the principal enzyme in regulating blood sugar levels. However, they could not purify and isolate the enzyme from the cellular extracts even after repeated experiments. Therefore, they tried a more laborious procedure of cell fractionation, by which they could detect the enzyme activity.
This was the moment of serendipitous discovery. To estimate the exact enzyme activity, they used a standardised enzyme acid phosphatase, and found that the activity was quite low (10% of the expected value). One day, the enzyme activity of purified cell fractions which had been refrigerated for five days was measured. To their surprise the enzyme activity increased back to that of the fresh sample. They got the same results no matter how many times they repeated the estimation. This led to a hypothesis that a membrane-like barrier restricted rapid access of the enzyme to its substrate, so that the enzymes were able to diffuse after a few days. They described the membrane-like barrier as a "saclike structure surrounded by a membrane and containing acid phosphatase."
An unrelated enzyme from the cell fraction had come from membranous fractions which were definitely cell organelles. In 1955, de Duve named them "lysosomes" to reflect their digestive properties. That same year, Alex B. Novikoff from the University of Vermont visited de Duve's laboratory, and successfully produced the first hard evidence of the organelle using electron microscopy. Using a staining method for acid phosphatase, de Duve and Novikoff further confirmed the location of the hydrolytic enzymes (acid hydrolases) of lysosomes.
Discovery of peroxisome
Serendipity followed de Duve for another major discovery. After confirmation of lysosome, de Duve's team was troubled by the existence of another enzyme urate oxidase in rat liver cell fraction. He was convinced that it did not belong to lysosome because it is not an acid hydrolase, typical of lysosomal enzymes, but still had similar distribution as acid phosphatase. In 1960 he further found that other enzymes such as catalase and D-amino acid oxidase were similarly distributed in cell fraction, and they were believed to be mitochondrial enzymes. (W. Bernhard and C. Rouillier had described such extra-mitochodrial organelles as microbodies, and believed that they were precursors to mitochondria.) de Duve discovered that these three enzymes exhibited similar chemical properties and were similar to those of other peroxide-producing oxidases.
He was skeptical of referring to them 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". He suggested that these enzymes belonged to the same cell organelle, but different from previously known organelles. But it would take some years before he publicised his hypothesis, as strong evidences were still lacking. In 1955 his team demonstrated similar cell fractions with same biochemical properties from the ciliated protozoan Tetrahymena pyriformis, from which it was indicated that these particles were new cell organelles unrelated to mitochondria. He presented his discovery at a meeting of the American Society for Cell Biology in 1955, and formally published in 1966 in which he created the name peroxisomes for the organelles as they are involved in peroxidase reactions. 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.
De Duve and his team went on to show that peroxisomes play important metabolic roles, including the β-oxidation of very long-chain fatty acids by a pathway different from that in mitochondria, and that they are members of a large family of evolutionarily related organelles present in diverse cells including plants, and protozoa, where they carry out distinct functions and have been given specific names, such as glyoxysomes and glycosomes.
Origin of cells
De Duve work has contributed to the emerging consensus that the endosymbiotic theory is correct; the idea which proposes that eukaryotic cell oraganelles originated as prokaryotic cells, which came to live inside eukaryotic cells as endosymbionts. According to his own version, eukaryotic cells with their structures and properties, including their ability to capture food by endocytosis and to digest it intracellularly, were developed first. Later prokaryotic cells were incorporated to form more organelles.
De Duve proposed that peroxisomes may have been the first endosymbionts, which allowed cells to withstand the growing amounts of free molecular oxygen in the Earth's atmosphere. Since peroxisomes have no DNA of their own, this proposal has much less evidence than the similar claims for mitochondria and chloroplasts. His later years were mostly devoted to origin of life studies, which he admitted as still a speculative field (see thioester).
De Duve was a prolific writer, both in technical and popular works. The most notable works are:
- A Guided Tour of the Living Cell (1984) ISBN 0-7167-5002-3
- La cellule vivante, une visite guidée, Pour la Science (1987) ISBN 978-2-902918-52-2
- Construire une cellule, Dunod (1990) ISBN 978-2-7296-0181-2
- Blueprint for a Cell: the Nature and Origin of Life (1991) ISBN 0-89278-410-5
- Poussière de vie, Fayard (1995) ISBN 978-2-213-59560-3
- Vital Dust: Life as a Cosmic Imperative (1996) ISBN 0-465-09045-1
- Life Evolving: Molecules, Mind, and Meaning (2002) ISBN 0-19-515605-6
- À l’écoute du vivant, éditions Odile Jacob, Paris (2002) ISBN 2-7381-1166-1
- Singularities: Landmarks on the Pathways of Life (2005) ISBN 978-0-521-84195-5
- Singularités: Jalons sur les chemins de la vie, éditions Odile Jacob (2005) ISBN 978-2-7381-1621-5
- Science et quête de sens, Presses de la Renaissance, (2005) ISBN 978-2-7509-0125-7
- Génétique du péché originel. Le poids du passé sur l’avenir de la vie, éditions Odile Jacob (2009) ISBN 978-2-7381-2218-6
- Genetics of Original Sin: The Impact of Natural Selection on the Future of Humanity (2010) ISBN 978-0-3001-6507-4
- De Jesus a Jesus... en passant par Darwin, éditions Odile Jacob (2011) ISBN 978-2-7381-2681-8
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. "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."
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.
De Duve married Janine Herman on 30 September 1943. Together they had had two sons, Thierry and Alain, and two daughters, Anne and Françoise. Janine died in 2008, aged 86.
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. He is survived by two sons and two daughters; two brothers, Pierre and Daniel; seven grandchildren; and two greatgrandchildren.
Awards and honours
De Duve won the Francqui Prize for Biological and Medical Sciences in 1960, and the Nobel Prize for Physiology or Medicine in 1974. King Baudouin of Belgium honoured him to Viscount in 1989. He was the recipient of the Gairdner Foundation International Award in 1967, and the Dr H.P. Heineken Prize for Biochemistry and Biophysics in 1973 from the Royal Netherlands Academy of Arts and Sciences.
He was elected a foreign associate of the National Academy of Sciences (United States) in 1975. He won the Harden Medal of the Biochemical Society of Great Britain in 1978; the Theobald Smith Award from the Albany Medical College in 1981; the Jimenez Diaz Award in 1985; the Innovators of Biochemistry Award from Medical College of Virginia in 1986; and the E.B. Wilson Medal from the in 1989.
He was also a member of the Royal Academies of Medicine and the Royal Academy of Sciences, Arts, and of Literature of Belgium; the Pontifical Academy of Sciences of the Vatican; the American Academy of Arts and Sciences; the French National Academy of Medicine; the Academy of Sciences of Paris; the Deutsche Akademie der Naturforscher Leopoldina; the American Philosophical Society. He was elected a Foreign Member of the Royal Society (ForMemRS) in 1988. In addition, he received honorary doctorates from eighteen universities around the world.
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.
De Duve was one of the founding members of the Belgian Society of Biochemistry and Molecular Biology, established on 15 September 1951.
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."
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.
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- Klionsky, DJ (2008). "Autophagy revisited: A conversation with Christian de Duve". Autophagy. 4 (6): 40–43. doi:10.4161/auto.6398. PMID 18567941.
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- Takano, T (1975). "Profile of Dr. C. De Duve, the 1974 Nobel prize winner in medical physiology". Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme. 20 (1): 77–78. PMID 1094499.
- James, J (1974). "The Nobel Prize in Medicine for Claude, Palade and De Duve". Nederlands Tijdschrift Voor Geneeskunde. 118 (52): 1949–51. PMID 4612387.
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- Florkin, M (1974). "Homage to Albert Claude and Christian de Duve, Nobel Prize laureates in medicine and physiology, 1974". Archives Internationales de Physiologie et de Biochimie. 82 (5): 807–15. doi:10.3109/13813457409072328. PMID 4142698.
- De Duve, C; Hooft, C (1968). "Quinquennial prizes of the medical sciences, period 1961-1965. Address by Prof. Chr. De Duve". Verhandelingen - Koninklijke Vlaamse Academie voor Geneeskunde van Belgie. 30 (7): 381–88. PMID 5712764.
- Kimball, CP; Murlin, J (1923). "Aqueous extracts of pancreas III. Some precipitation reactions of insulin". The Journal of Biochemistry. 58: 337–46.
- Bouckaert, JP; de Duve, C (947). "The action of insulin". Physiological Reviews. 27 (1): 39–71. PMID 20282153.
- de Duve, C (1951). "Glucagon, the hyperglycemic factor of the pancreas". Acta Physiologica et Pharmacologica Neerlandica. 2 (2): 311–14. PMID 14902502.
- de Duve, C; Vuylsteke, CA (1953). "New research on glucagon". Journal de Physiologie (in French). 45 (1): 107–108. PMID 13062154.
- de Duve, C; Vuylsteke, CA (1953). "glycogenolytic factor of the pancreas". Archives Internationales de Physiologie (in French). 61 (1): 107–108. doi:10.3109/13813455309150157. PMID 13058530.
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- Lefèbvre, P. J. (2011). "Early milestones in glucagon research". Diabetes, Obesity and Metabolism. 13: 1–4. doi:10.1111/j.1463-1326.2011.01437.x. PMID 21824250.
- Vuylsteke, CA; de Duve, C (1953). "Influence of glucagon on the action of insulin". Archives Internationales de Physiologie (in French). 61 (2): 275–76. doi:10.3109/13813455309147742. PMID 13081243.
- de Duve, C (1953). "Glucagon; the hyperglycaemic glycogenolytic factor of the pancreas". The Lancet. 265 (6777): 99–104. doi:10.1016/s0140-6736(53)90052-x. PMID 13070549.
- Berthet, J; de Duve, C (1951). "Tissue fractionation studies. I. The existence of a mitochondria-linked, enzymically inactive form of acid phosphatase in rat-liver tissue". The Biochemical Journal. 50 (2): 174–181. PMC 1197627
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- Berthet, J; Berthet, L; Appelmans, F; de Duve, C (1951). "Tissue fractionation studies. II. The nature of the linkage between acid phosphatase and mitochondria in rat-liver tissue". The Biochemical Journal. 50 (2): 182–189. PMC 1197628
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- Beaufay, H; de Duve, C (1954). "The hexosephosphatase system. VI. Attempted fractionation of microsomes containing glucose-6-phosphatase". Bulletin de la Société de Chimie Biologique (in French). 36 (11–12): 1551–1568. PMID 14378854.
- Appelmans, F; Wattiaux, R; de Duve, C (1955). "Tissue fractionation studies. 5. The association of acid phosphatase with a special class of cytoplasmic granules in rat liver". The Biochemical Journal. 59 (3): 438–445. PMC 1216263
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- Castro-Obregon, Susana (2010). "The Discovery of Lysosomes and Autophagy". Nature Education. 3 (9): 49.
- De Duve, C (2005). "The lysosome turns fifty". Nature Cell Biology. 7 (9): 847–49. doi:10.1038/ncb0905-847. PMID 16136179.
- Novikoff, AB; Beaufay, H; De Duve, C (1956). "Electron microscopy of lysosomerich fractions from rat liver". The Journal of Biophysical and Biochemical Cytology. 2 (4 Suppl): 179–84. doi:10.1083/jcb.2.4.179. PMC 2229688
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- de Duve, C; Bueaufay, H; Jacques, P; Rahman-LiLI, Y; Sellinger, OZ; Wattiuaux, R; de Connick, S (1960). "Intracellular localization of catalase and of some oxidases in rat liver". Biochimica et Biophysica Acta. 40: 186–187. doi:10.1016/S0006-3002(89)80026-5. PMID 13814739.
- Bernhard, W; Rouillier, C (1956). "Microbodies and the problem of mitochondrial regeneration in liver cells". The Journal of Biophysical and Biochemical Cytology. 2 (4 Suppl): 355–360. PMC 2229729
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- De Duve, C; Wattiaux, R; Baudhuin, P (1962). "Distributionof enzymes between subcellular fractions in animal tissues". Advances in Enzymology and Related Subjects of Biochemistry. 24: 291–358. doi:10.1002/9780470124888.ch6. PMID 13884182.
- Baudhuin, P; Beaufay, H; De Duve, C (1965). "Combined biochemical and morphological study of particulate fractions from rat liver. Analysis of preparations enriched in lysosomes or in particles containing urate oxidase, D-amino acid oxidase, and catalase". The Journal of Cell Biology. 26 (1): 219–243. doi:10.1083/jcb.26.1.219. PMC 2106697
. PMID 4379260.
- Bonetta, L. (2005). "Seeing peroxisomes". The Journal of Cell Biology. 169 (5): 705. doi:10.1083/jcb1695fta2. PMC 2254818
- de Duve, C; Baudhuin, P (1966). "Peroxisomes (microbodies and related particles)". Physiological Reviews. 46 (2): 323–57. PMID 5325972.
- Leighton, F; Poole, B; Beaufay, H; Baudhuin, P; Coffey, JW; Fowler, S; De Duve, C (1968). "The large-scale separation of peroxisomes, mitochondria, and lysosomes from the livers of rats injected with triton WR-1339. Improved isolation procedures, automated analysis, biochemical and morphological properties of fractions". The Journal of Cell Biology. 37 (2): 482–513. doi:10.1083/jcb.37.2.482. PMC 2107417
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- de Duve, D (1969). "The peroxisome: a new cytoplasmic organelle". Proceedings of the Royal Society of London B. 173 (1030): 71–83. doi:10.1098/rspb.1969.0039. PMID 4389648.
- Duve, Christian de (1982). "Peroxisomes and related particles in historical perspective". Annals of the New York Academy of Sciences. 386 (1): 1–4. doi:10.1111/j.1749-6632.1982.tb21402.x. PMID 6953840.
- de Duve, C (1996). "The Peroxisome in Retrospect". Annals of the New York Academy of Sciences. 804 (1): 1–10. doi:10.1111/j.1749-6632.1996.tb18603.x. PMID 8993531.
- de Duve, Christian (2007). "The origin of eukaryotes: a reappraisal". Nature Reviews Genetics. 8 (5): 395–403. doi:10.1038/nrg2071. PMID 17429433.
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