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 Catholic University of Leuven was contentiously
split into two separate universities along linguistic lines. De Duve chose to join the French-speaking side,
Université catholique de Louvain. He took
emeritus status at the
University of 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 The hormone
glucagon was discovered by C.P. Kimball and John R. Murlin in 1923 as a
hyperglycaemic (blood-sugar elevating) substance among the
pancreatic extracts. 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 the
Eli 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. By then de Duve had joined
Carl Cori and
Gerty Cori 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. De Duve's original hypothesis that glucagon was produced by pancreatic alpha cells was proven correct when he demonstrated that selectively
cobalt-damaged alpha cells stopped producing glucagon in
guinea pigs; he finally isolated the purified hormone in 1953, including those from birds. 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.
Discovery of lysosome Christian de Duve and his team continued studying the insulin mechanism-of-action in liver cells, focusing on the enzyme
glucose 6-phosphatase, the key enzyme in sugar metabolism (
glycolysis) and the target of insulin. They found that G6P was the principal enzyme in regulating
blood sugar levels, 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. 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." 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. That same year,
Alex B. Novikoff from the
University of Vermont visited de Duve's laboratory, and, using
electron 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.
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. (W. Bernhard and C. Rouillier had described such extra-mitochondrial organelles as
microbodies, and believed that they were precursors to mitochondria.) de Duve noted the three enzymes exhibited similar chemical properties and were similar to those of other peroxide-producing oxidases. 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". He suggested that these enzymes belonged to the same cell organelle, but one different from previously known organelles. and formally published in 1966, creating 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's work has contributed to the emerging consensus towards accepting the
endosymbiotic theory; which idea proposes that organelles in
eukaryotic cells originated as certain
prokaryotic cells that came to live inside eukaryotic cells as
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. 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
DNA of their own, this proposal has much less evidence than similar claims for mitochondria and chloroplasts. His later years were mostly devoted to
origin of life studies, which he admitted was still a speculative field (see
thioester).
Publications 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) •
La cellule vivante, une visite guidée, Pour la Science (1987) •
Construire une cellule, Dunod (1990) •
Blueprint for a Cell: the Nature and Origin of Life (1991) •
Poussière de vie, Fayard (1995) •
Vital Dust: Life as a Cosmic Imperative (1996) •
Life Evolving: Molecules, Mind, and Meaning (2002) • ''À l'écoute du vivant'', éditions Odile Jacob, Paris (2002) •
Singularities: Landmarks on the Pathways of Life (2005) •
Singularités: Jalons sur les chemins de la vie, éditions Odile Jacob (2005) •
Science et quête de sens, Presses de la Renaissance, (2005) • ''Génétique du péché originel. Le poids du passé sur l'avenir de la vie'', éditions Odile Jacob (2009) •
Genetics of Original Sin: The Impact of Natural Selection on the Future of Humanity, Yale University Press (2010) •
De Jesus a Jesus... en passant par Darwin, éditions Odile Jacob (2011) • ''Sept vies en une: Mémoires d'un prix Nobel'', Éditions Odile Jacob (2013) •
Sur la science et au-delà: [entretien] avec Jean Vandenhaute, Éditions Odile Jacob (2013) ==Personal life==