The son of Belgian refugees during theFirst World War, de Duve was born inThames Ditton, Surrey, England.[8] His family returned to Belgium in 1920. He was educated by theJesuits atOur Lady College, Antwerp, and studied medicine at theCatholic University of Louvain. Upon earning hisMD in 1941, he joined research in chemistry, working oninsulin and its role indiabetes mellitus. His thesis earned him the highest university degreeagrégation de l'enseignement supérieur (equivalent to PhD) in 1945.[9]
With his work on the purification ofpenicillin, he obtained an MSc degree in 1946. He went for further training under later Nobel Prize winnersHugo Theorell at theKarolinska Institutet in Stockholm, andCarl andGerti Cori at theWashington University in St. Louis. He joined the faculty of medicine at Leuven in 1947. In 1960 he was invited to the Rockfeller Institute (nowRockefeller University). With mutual arrangement with Leuven, he became professor in both universities from 1962, dividing his time between Leuven and New York. In 1974, the same year he received his Nobel Prize, he founded the ICP, which would later be renamed the de Duve Institute.[10] He became emeritus professor of theUniversity of Louvain in 1985, and of Rockefeller in 1988.[11]
De Duve was born of an estate agent Alphonse de Duve and wife Madeleine Pungs in the village ofThames Ditton, nearLondon. 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.[1]
He was educated by theJesuits atOnze-Lieve-Vrouwinstituut inAntwerp, before studying at theCatholic University of Louvain in 1934.[15] He wanted to specialize inendocrinology and joined the laboratory of the Belgian physiologist Joseph P. Bouckaert, whose primary interest was one insulin.[16] During his last year at medical school in 1940, the Germans invaded Belgium. He wasdrafted to the Belgian army, and posted in southernFrance as medical officer. There, he was almost immediately taken asprisoner 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".[9]
He immediately continued his medical course, and obtained hisMD in 1941 from Leuven. After graduation, de Duve continued his primary research oninsulin and its role inglucose metabolism. He (with Earl Sutherland) made an initial discovery that a commercial preparation of insulin was contaminated with anotherpancreatic hormone, the insulin antagonistglucagon.[16] 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 titledGlucose, Insuline et Diabète (Glucose, Insulin and Diabetes) published in 1945, simultaneously inBrussels andParis. The book was condensed into a technical dissertation which earned him the most advanced degree at the university levelagrégation de l'enseignement supérieur (an equivalent of a doctorate – he called it "a sort of glorified PhD") in 1945.[9] His thesis was followed by a number of scientific publications.[17] He subsequently obtained aMSc in chemistry in 1946, for which he worked on the purification ofpenicillin.[18]
To enhance his skill in biochemistry, he trained in the laboratory ofHugo Theorell (who later won The Nobel Prize in Physiology or Medicine in 1955) at theNobel Medical Institute in Stockholm for 18 months during 1946–47. In 1947, he received a financial assistance asRockefeller Foundation fellow and worked for six months withCarl andGerti Cori atWashington University in St. Louis (the husband and wife were joint winners of The Nobel Prize in Physiology or Medicine in 1947).[19]
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 nowRockefeller 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.[20]
The hormoneglucagon was discovered by C.P. Kimball and John R. Murlin in 1923 as ahyperglycaemic (blood-sugar elevating) substance among thepancreatic extracts.[35] The biological importance of glucagon was not known and the name itself was essentially forgotten. It was a still a mystery at the time de Duve joined Bouckaert at Leuven University to work on insulin. Since 1921, insulin was the first commercial hormonal drug originally produced by theEli Lilly and Company, but their extraction methods introduced an impurity that caused mild hyperglycaemia, the very opposite of what was expected or desired. In May 1944 de Duve realised that crystallisation could remove the impurity. He demonstrated that Lilly's insulin process was contaminated, showing that, when injected into rats, the Lilly insulin caused initial hyperglycaemia and the Danish Novo insulin did not. Following his research published in 1947, Lilly upgraded its methods to eliminate the impurity.[36] By then de Duve had joinedCarl Cori andGerty Cori at Washington University in St. Louis, where he worked with a fellow researcherEarl Wilbur Sutherland, Jr., who later won the Nobel Prize in Physiology or Medicine in 1971.[16]
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 thegastric mucosa and certain other parts of the digestive tract. Further, they found that the hormone was produced frompancreatic islets by cells differing from the insulin-producingbeta cells; presumably these werealpha 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 ofglycogen in the liver—the process known asglycogenolysis—by which more sugars are produced and released into the blood.[37]
De Duve's original hypothesis that glucagon was produced by pancreatic alpha cells was proven correct when he demonstrated that selectivelycobalt-damaged alpha cells stopped producing glucagon inguinea pigs;[38] he finally isolated the purified hormone in 1953,[39] including those from birds.[40][41][42][43]
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, (seehomeostasis). 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.[44][45]
Christian de Duve and his team continued studying the insulin mechanism-of-action in liver cells, focusing on the enzymeglucose 6-phosphatase, the key enzyme in sugar metabolism (glycolysis) and the target of insulin. They found that G6P was the principal enzyme in regulatingblood sugar levels,[46][47] but, they could not, even after repeated experiments, purify and isolate the enzyme from the cellular extracts. So they tried the more laborious procedure ofcell fractionation to detect the enzyme activity.[48]
This was the moment of serendipitous discovery. To estimate the exact enzyme activity, the team adopted a procedure using a standardised enzymeacid 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 itssubstrate, 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."[49][50]
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.[51] That same year,Alex B. Novikoff from theUniversity of Vermont visited de Duve's laboratory, and, usingelectron microscopy, successfully produced the first visual evidence of the lysosome organelle. Using a staining method for acid phosphatase, de Duve and Novikoff further confirmed the location of the hydrolytic enzymes (acid hydrolases) of lysosomes.[22][52]
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 enzymeurate 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 ascatalase andD-amino acid oxidase), that were similarly distributed in the cell fraction—and it was then thought that these were mitochondrial enzymes.[53] (W. Bernhard and C. Rouillier had described such extra-mitochondrial organelles asmicrobodies, and believed that they were precursors to mitochondria.)[54] de Duve noted the three enzymes exhibited similar chemical properties and were similar to those of other peroxide-producing oxidases.[55]
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".[56] He suggested that these enzymes belonged to the same cell organelle, but one different from previously known organelles.[22] 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 protozoanTetrahymena pyriformis; thus, it was indicated that the particles were undescribed cell organelles unrelated to mitochondria. He presented his discovery at a meeting of theAmerican Society for Cell Biology in 1955,[57] and formally published in 1966, creating the name peroxisomes for the organelles as they are involved in peroxidase reactions.[58] In 1968 he achieved the first large-scale preparation of peroxisomes, confirming thatl-α hydroxyacid oxidase, d-amino acid oxidase, and catalase were all the unique enzymes of peroxisomes.[59][60]
De Duve and his team went on to show that peroxisomes play important metabolic roles, including theβ-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 asglyoxysomes andglycosomes.)[16][61][62]
De Duve's work has contributed to the emerging consensus towards accepting theendosymbiotic theory; which idea proposes that organelles ineukaryotic cells originated as certainprokaryotic cells that came to live inside eukaryotic cells asendosymbionts. 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.[63]
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 noDNA of their own, this proposal has much less evidence than similar claims for mitochondria and chloroplasts.[64][65] His later years were mostly devoted toorigin of life studies, which he admitted was still a speculative field (seethioester).[66][67]
De Duve was brought up as aRoman Catholic. In his later years he tended towardsagnosticism, if not strictatheism.[68][69] 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."[70] "It would be an exaggeration to say I'm not afraid of death", he explicitly said to a Belgian newspaperLe Soir just a month before his death, "but I'm not afraid of what comes after, because I'm not a believer."[71][72]
He strongly supportedbiological evolution as a fact, and dismissive ofcreation science andintelligent design, as explicitly stated in one of his last books,Genetics of Original Sin: The Impact of Natural Selection on the Future of Humanity (French original 2009). He was among the seventy-eight Nobel laureates in science to endorse the effort to repeal theLouisiana Science Education Act of 2008.[73]
His family (von Duve) came fromHanover and settled in Belgium after theBattle of Waterloo. De Duve married Janine Herman on 30 September 1943. Together they had had two sons, one of whom is noted art professorThierry de Duve, and two daughters.
De Duve died on 4 May 2013, at his home in Nethen, Belgium, aged 95. He decided to end his life by legaleuthanasia, performed by two doctors and in the presence of his four children. He had been long suffering fromcancer andatrial fibrillation, and his health problems were exacerbated by a recent fall in his home.[74][13][14][75]
De Duve was cremated as he had willed, and his ashes were distributed among family members and friends.
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 is remembered as an inventor of important scientific terminology. He coined the wordlysosome in 1955,peroxisome in 1966, andautophagy,endocytosis, andexocytosis in one instance at theCiba Foundation Symposium on Lysosomes held in London during 12–14 February 1963, while he, "was in a word-coining mood."[22][86]
De Duve's life, including his work resulting in a Nobel Prize, and his passion for biology is the subject of a documentary filmPortrait 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]
^Turk, V (2012). "Special issue: Proteolysis 50 years after the discovery of lysosome in honor of Christian de Duve".Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics.1824 (1):1–2.doi:10.1016/j.bbapap.2011.11.001.PMID22142840.
^Berthet, J (2007). "Scientific work of Christian de Duve".Bulletin et Mémoires de l'Académie Royale de Médecine de Belgique.12 (10–12):499–504.PMID18557391.
^Berthet, J (1994). "Introduction of Professor Christian De Duve, Nobel Prize in Medicine and Physiology in 1974".Bulletin et Mémoires de l'Académie Royale de Médecine de Belgique.149 (12):476–80.PMID8563687.
^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.PMID1094499.
^James, J (1974). "The Nobel Prize in Medicine for Claude, Palade and De Duve".Nederlands Tijdschrift voor Geneeskunde.118 (52):1949–51.PMID4612387.
^Olsen, BR; Lie, SO (1974). "Nobel prize in medicine 1974 (Albert Claude, George Palade, Christian de Duve)".Tidsskrift for den Norske Laegeforening.94 (34–36):2400–03.PMID4614493.
^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.PMID5712764.
^de Duve, C (1951). "Glucagon, the hyperglycemic factor of the pancreas".Acta Physiologica et Pharmacologica Neerlandica.2 (2):311–14.PMID14902502.
^de Duve, C; Vuylsteke, CA (1953). "New research on glucagon".Journal de Physiologie (in French).45 (1):107–108.PMID13062154.
^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.PMID13058530.
^Vuylsteke, CA; de Duve, C (1953). "Glucagon content of avian pancreas".Archives Internationales de Physiologie (in French).61 (2):273–274.doi:10.3109/13813455309147741.PMID13081242.
^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.PMID13081243.
^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.PMID14378854.
^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.PMID13814739.
^De Duve, C; Wattiaux, R; Baudhuin, P (1962). "Distribution of Enzymes Between Subcellular Fractions in Animal Tissues".Advances in Enzymology and Related Areas of Molecular Biology. Vol. 24. pp. 291–358.doi:10.1002/9780470124888.ch6.ISBN978-0-470-12488-8.PMID13884182.{{cite book}}:ISBN / Date incompatibility (help);|journal= ignored (help)
^De Duve, C (1998). "Constraints on the origin and evolution of life".Proceedings of the American Philosophical Society.142 (4):525–532.PMID11623597.
^de Duve, C (1998). "Reflections on the origin and evolution of life".Comptes Rendus des Séances de la Société de Biologie et de Ses Filiales (in French).192 (5):893–901.PMID9871802.
