September 2013

Christian de Duve, 1917 – 2013

Christian de Duve
Image courtesy of The Rockefeller University

Christian de Duve, one of Belgium’s greatest scientists and winner of the 1974 Nobel Prize for describing the structure and function of lysosomes and peroxisomes, died at his home on May 4. He was 95 and elected to die by euthanasia, which is legal in Belgium.
 
De Duve was born in 1917 in Thames-Ditton, England, where his parents had gone to escape the ravages of World War I. He was educated in Belgium at a Jesuit school, where the classes were taught in either French or Flemish.
 
He attended the medical school of the Catholic University of Louvain, earning an M.D. in 1941, and went on to conduct research on the action of insulin with Joseph Bouckaert as his mentor; Bouckaert was unusual as an avid reader of the Encyclopedia Britannica. They measured the amount of glucose infused to maintain the blood glucose at a constant level.
 
De Duve was a proponent of insulin action on the liver, but his findings were complicated by the presence of glucagon in most preparations of insulin at that time. He wrote up his work in a book titled “Glucose, Insuline et Diabète,” with 400 pages and 1,200 references, which was submitted as the equivalent of a Ph.D. and published in 1945. He earned an M.S. in chemistry the next year.
 
He completed a short stint in the Belgian army during World War II and was held briefly in a prison camp, from which he managed to escape.
 
At the end of the war, he went to Stockholm to work with Hugo Theorell, an enzymologist who later won the Nobel Prize. He wondered why Theorell accepted him even though he had little knowledge of biochemistry. He attributed this to Theorell’s great love of the French language. De Duve was fluent in four languages, which he attributed to his extensive travel throughout Europe and considered an asset in his scientific career.
 
De Duve then decided to go to the Cori laboratory at the Washington University School of Medicine in St. Louis, but Carl Cori at first was reluctant to take him, because the Cori group had found that insulin stimulated the breakdown of liver glycogen, whereas de Duve had evidence that insulin caused the uptake of glucose by the liver. The dilemma was solved when de Duve, working with Earl Sutherland in the Cori lab, showed that the glycogenolytic action of insulin was caused by a contaminant that was identified as glucagon. This observation later led to Sutherland’s discovery of cyclic AMP, for which he won the Nobel Prize.
 
De Duve returned in 1947 to the Catholic University of Louvain to teach physiology and do research on glucose-6-phosphatase. He found that the enzyme seemed to be attached to an intracellular structure, which now is recognized as the endoplasmic reticulum. His group also monitored another enzyme termed acid phosphatase because it interfered with their results. They set about defining its nature using differential centrifugation. The fraction containing this phosphatase exhibited an interesting property: It exhibited low activity initially, but this markedly increased with storage. They also found that when particles in the fraction were disrupted, the enzyme was released, which indicated that its latency was due to its enclosure within vesicles.

The next phase of the research was to define the nature of the subcellular particles. De Duve’s group again used differential centrifugation and analyzed the various fractions for enzyme markers. A different procedure, namely isotonic sucrose, was used to prepare the starting homogenates, and gentler homogenization was used to preserve the structure of the particles.
 
De Duve was surprised to find that the enzyme was in both the mitochondrial and microsomal fractions, and he thought he was dealing with a new particle. He started varying the centrifugation protocol, and serendipity intervened when one of the centrifuges broke down and had to be used at a lower power.
 
This yielded enzyme-containing particles that sedimented midway between mitochondria and microsomes. The new particles were called lysosomes, a term that de Duve later regretted because of its possible confusion with the enzyme lysozyme. Interestingly, lysosomes had been discovered earlier by Russian zoologist and Nobel laureate Elie Metchnikoff as vacuoles involved in digestion in protozoa.
 
De Duve searched for other enzymes associated with lysosomes and found some acid hydrolases. Later, more than 50 hydrolytic enzymes were found to be contained within lysosomes, and these organelles were recognized as major sites for the digestion of intracellular macromolecules.
 
The medical importance of lysosomes emerged when a variety of diseases were traced to lysosomal enzyme deficiencies. Pompe’s disease was recognized initially. It causes the accumulation of glycogen due to deficiency of an acid α-glucosidase. Later, other devastating diseases were ascribed to deficiencies of lysosomal enzymes leading to the accumulation of glucocerebrosides, glycolipids and sphingomyelin.
 
After his work on lysosomes, de Duve studied urate oxidase, which he found had very different properties to acid phosphatase. Work on this enzyme led to the identification of a new particle, which he called the peroxisome.
 
In 1962, de Duve began to tire of his duties at the Catholic University and took a position at what was then the Rockefeller Institute, now The Rockefeller University, in New York. He split his time between the two institutions, and when the Catholic University was divided, he commuted between New York and Brussels, where the new medical school was located.

Excerpt from “My Love Affair with Insulin”

“It all started with a chance encounter in the fall of 1935. As a second-year medical student at the Catholic University of Louvain (Belgium) with time on my hands, I conformed to the local tradition according to which ‘good students’ would ‘do a laboratory,’ which meant that they joined the laboratory of one of their professors and participated on a voluntary basis in whatever research was going on. This arrangement suited both parties. The professors got free manpower. The students kept out of mischief, gained experience, had fun, and (if they persevered long enough) could write up a dissertation and use it to compete for a traveling fellowship. Many a scientific career was launched in this way.”
 
Click here to read the rest of Christian de Duve’s 2004 scientific memoir in The Journal of Biological Chemistry.

To strengthen the new school, he conceived of the establishment of an international, multidisciplinary research institute. He founded it in the early 1970s on the basis of three principles: priority of basic research and freedom of investigators, special attention to medical benefits resulting from basic discoveries, and multidisciplinary collaboration within a critical mass of competency. It was called the International Institute of Cellular and Molecular Pathology. It began with only four research groups but grew to include 270 investigators, and its cumbersome name later was changed to the de Duve Institute.
 
De Duve received the Nobel Prize for physiology or medicine in 1974 along with Albert Claude and George E. Palade, both of Rockefeller, “for their discoveries concerning the structural and functional organization of the cell.”
 
In 1985, de Duve became an emeritus professor at the Catholic University, and he retired as president of the institute in 1991.
 
In his retirement, he wrote several books. One of these was scientific, “A Guided Tour of the Living Cell,’’ and one was more philosophical, “Genetics of Original Sin: The Impact of Natural Selection on the Future of Humanity.”

John ExtonJohn Exton (john.exton@mcmail.vanderbilt.edu) is a professor of molecular physiology and biophysics and pharmacology at the Vanderbilt University Medical Center.


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1 Comments

  • Dr. Exton,
    Thank you for this retrospective on Prof. de Duve. I spent a year in his Dept in Louvain working with Dr. Pierre Jacques on the possible role of lysomes in the kidney calcification of magnesium deficiency in rats. The hypothesis proved to be negative but the experience was unforgettable.
    One of my classmates at Virginia Tech was Dr. John Hash who for many years was Dean of Research at Vanderbilt. If you know him, would you please pass on my regards.
    Sincerely,
    George Ed Bunce

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