"Exploring Cells With a Centrifuge": The Discovery of the Lysosome

Within all animal cells, the lysosome functions as the sanitation department: it digests, recycles and disposes of such materials as worn-out organelles and engulfed bacteria and viruses. A membrane seals off the lysosome's acidic environment, preventing its enzymes from harming the rest of the cell. One of these enzymes, acid phosphatase, provided Christian de Duve (1917- ) with a clue that led him, in the early 1950s, to discover the lysosome entirely by biochemical methods. With electron microscopy, de Duve and colleagues then imaged lysosomes in cell fractions. This basic discovery underlies the current understanding of several inherited disorders caused by defective lysosomal proteins, including Tay-Sach's disease and Gaucher's disease. For his "discoveries concerning the structural and functional organization of the cell," de Duve received the Nobel Prize in 1974, shared with Albert Claude (1899-1983) and George E. Palade (1912-2008).

de Duve, Christian
Photo by Ingbet Grüttner

A serendipitous observation set de Duve on the path to the lysosome. Following a long interest in insulin, he was studying the metabolism of carbohydrates in the rat liver in 1949, when he turned to the methods of cell fractionation by differential centrifugation pioneered by Albert Claude at Rockefeller. As he later wrote, "All we wanted was to know something about the localization of the enzyme glucose 6-phosphatase, which we thought might provide a possible clue to the mechanism of action, or lack of action, of insulin on the liver cell." They found first that glucose 6-phosphatase was associated with microsomal particles, and could serve as a marker for that organelle. They also noticed that another enzyme, acid phosphatase, was hardly detectable with fresh cell homogenates but present in large quantities after further processing. This led them to hypothesize that this phantom enzyme was sealed in a sac, or membrane, that could break and release it.

As they analyzed the distribution of several enzymes in cell fractions, de Duve and coworkers developed refined fractionation techniques and also investigated and extended the method's theoretical underpinnings. By 1955 the group had identified four additional hydrolytic enzymes—enough evidence to propose the existence of a new group of particles, or organelles, which they called lysosomes. Collaborating with Alex Novikoff, they made electron micrographs of the lysosome-rich fractions in which the particles appeared as "dense bodies, surrounded by a membrane." de Duve's group continued to develop methods and instruments for cell fractionation. de Duve later discovered another organelle—the peroxisome—which contains enzymes that metabolize fatty acids in most eukaryotic cells.

Biochemical model representing rat-liver lysosomes, first described by de Duve… [et al.] in 1955. Copy of old slide

In 1974 de Duve founded the International Institute of Cellular and Molecular Pathology at the Catholic University of Louvain, a biomedical research institute modeled on The Rockefeller University, with the goal of translating basic discoveries into medical advances. It was renamed the de Duve Institute in 2005. de Duve's interests in the last two decades have turned to the origin and evolution of life, and he has authored three books on this subject (see Further Reading below).

Christian René de Duve received the MD from the Catholic University of Louvain (1941). He pursued further training in chemistry, and then in biochemistry, spending 18 months in the Stockholm laboratory of Hugo Theorell (Nobel Prize, 1955). He then went to the Washington University School of Medicine, where he collaborated for six months with Earl Sutherland (Nobel Prize, 1971) in the laboratory of Carl and Gerty Cori (Nobel Prize, 1947). In 1947 de Duve joined the faculty of the Catholic University of Louvain, and became, in 1951, professor and head of the department of physiological chemistry. In 1962 he was appointed professor at The Rockefeller University, and for decades maintained laboratories in both New York City and Louvain. In addition to the Nobel Prize (1974) de Duve's achievements have been recognized with the Francqui Prize for Biological and Medical Sciences (1960) and the Heineken Prize for Biochemistry and Biophysics (1973). He became emeritus at the University of Louvain in 1985 and at Rockefeller in 1988; he remained president of the ICP until 1991.

Selected Publications

Appelmans F, Wattiaux R, de Duve C. Tissue fractionation studies. 5. The association of acid phosphatase with a special class of cytoplasmic granules in rat liver. Biochem J, 1955, 59: 438–445

de Duve C, Pressman BC, Gianetto R, Wattiaux R, and Appelmans F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J, 1955, 60: 604–617

Novikoff AB, Beaufay H, and de Duve C. Electon microscopy of lysosome-rich fractions from rat liver. J Biophys Biochem Cytol, 1956, 2(4): 179–184

de Duve C. J Theoret Biol, 1964, 6: 33

de Duve C and Wattiaux R. Functions of lysosomes. Annu Rev Physiol, 1966, 28: 435-492

de Duve C. The peroxisome: a new cytoplasmic organelle. Proc R Soc Lond, B, Biol Sci, 1969, 173: 71-83

Further Reading

de Duve C. The lysosome in retrospect. In Dingle JT and Fell HB, eds, Lysosomes in Biology and Pathology. Amsterdam: North-Holland Publishing Company, 1969, pp. 3-40

de Duve C. Tissue fractionation: Past and present. J Cell Biol, 1971, 50: 20D-55D

de Duve C and Beaufay H. A short history of tissue fractionation. J Cell Biol, 1981, 91(3): 293s

de Duve, C. The peroxisome in retrospect. Ann NY Acad Sci, 1996, 804: 1–10

de Duve C. My love affair with insulin. J Biol Chem, 2004, 279: 21679-21688

de Duve C. The lysosome turns fifty. Nat Cell Biol, 2005, 47: 847–849

de Duve C. A Guided Tour of the Living Cell (Scientific American Books, 1984)

de Duve C. Blueprint For a Cell: The Nature and Origin of Life (Neil Patterson Publishers, 1991)

de Duve C. Vital Dust: Life As a Cosmic Imperative (Basic Books, 1995)

de Duve C. Life Evolving: Molecules, Mind, and Meaning (Oxford Univ. Press, 2002)

de Duve C. Singularities: Landmarks on the Pathways of Life (Cambridge Univ. Press, 2005)

de Duve C. Genetics of Original Sin: The Weight of the Past on the Future of Life (Yale Univ. Press, 2010)

Bainton DF. The discovery of lysosomes. J Cell Biol, 1981, 91: 66s-76s

Bowers WE. Christian de Duve and the discovery of lysosomes and peroxisomes. Trends Cell Biol, 1998, 8: 330-333
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCX-3TXK86D-F&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1& _urlVersion=0&_userid=10&md5=5107566baa178820aa18117b8934ea7c

Wells W. From the archive: Catching sight of lysosomes. J Cell Biol, 2005, 168: 174

A short history of cell fractionation: the original description of the lysosome Kathryn E. Howell Biochem J, 2006, December: 31-34


Christian de Duve International Institute of Cellular and Molecular Pathology

Nobel Prize in Physiology or Medicine, 1974

Interview with Christian de Duve, 2000

Interview with Christian de Duve, 2005: http://www.vega.org.uk/video/programme/126

Interview with Christian de Duve: http://www.peoplesarchive.com/browse/movies/6541/en/off/