Albert Claude

Biologist

• Born: August 24, 1899
• Birthplace: Longlier, Belgium
• Died: May 22, 1983
• Place of death: Brussels, Belgium

Belgian American cell biologist

Albert Claude developed many of the modern procedures used in cell fractionation and separation critical for identification and analysis of cellular components. His isolation of mitochondria was critical in understanding their function.

Born: August 24, 1899; Longlier, Belgium

Died: May 22, 1983; Brussels, Belgium

Primary field: Biology

Specialties: Cellular biology; biochemistry

Early Life

Albert Claude was born August 24, 1899, in Longlier, Belgium, the youngest of four children. When Claude was seven years old his mother died from breast cancer, after which the family moved to the steel-making region of Athus near the border of Luxembourg. Forced to leave his primary school in Longlier, Claude began working at a local mill, largely ending his formal early education. Claude’s stay in Athus was short, as he was forced to return to Longlier to help with the care of an infirm uncle.

In 1914 Belgium was invaded by Germany during the early weeks of World War I. Fluent in German, Claude joined the Belgian underground as an agent of British intelligence. He was captured twice by the Germans but still managed to survive the war. Claude never completed his early education but was still admitted in 1922 to the University of Liège. Since a medical career appeared the best option for his life’s work, Claude entered the medical school at the university, obtaining his medical degree in 1928. As a postdoctoral student in 1928 and 1929 Claude worked at the Institut für Krebsforschung (Institute for Cancer Research) in Germany, and then at the Kaiser Wilhelm Institute, where he learned cell-culture techniques under the guidance of scientist Albert Fischer. During the summer of 1929, Simon Flexner, director of the Rockefeller Institute in New York, offered Claude a position in New York, where Claude would remain for most of his professional career. In 1935, he married Julia Gilder. Though the couple eventually divorced, they did have one daughter, Philippa. Claude became a naturalized American citizen in 1941.

Life’s Work

Claude joined the laboratory of James B. Murphy, head of the pathology department at the Rockefeller Institute, where he was funded through the Belgian American Educational Foundation. Murphy had previously worked with pathologist Peyton Rous at the institute in the years after Rous had isolated a filterable agent that transmitted tumors between chickens. Frustrated with attempting to identify similar agents in mammals, Rous had moved on to other studies by the 1930s. Murphy, however, continued to investigate the nature of the agent, the specific project on which Claude would work.

Since the modern concept of a virus was still unknown in the 1930s, Murphy and Claude assumed the agent was an internal component of the cell, much like an enzyme. During most of the 1930s Claude attempted various ways of cell fractionation—the separation of cell organelles and components—to isolate and characterize the agent. He experienced partial success as early as 1938, when he reported the presence of protein, lipid, and RNA (ribonucleic acid) in the most active portion of the extract. At the time, nucleic acids had not yet been shown to be the source of genetic information in the cell, and it was not until the 1950s that RNA would be shown to be the genetic information in the Rous virus. Consequently Claude’s interpretation of his results was that the agent was simply a mixture of the identified constituents. He is generally credited as the first scientist to use chemical analysis to isolate a cancer virus.

While Claude never identified the agent found in tumor tissue, the observations he made of concentrated tumor extract ironically led him in a more significant direction. When he compared tumor extracts with normal tissues he observed in each an unusual granular material. Since the same material was observed in normal cells Claude abandoned his work with tumor tissue.

Claude spent most of the next decade of his career in modifying his cell fractionation techniques in order to study the granular material—which he called microsomes—as well as other cell structures or organelles. Separation of nuclei was comparatively easy, given their large size, and had already been accomplished by other scientists. Claude’s challenge lay in trying to had difficulty even observing once it was suspended in buffer.

Claude eventually solved this problem, simultaneously developing a method to separate larger granules, identified as mitochondria, from the smaller microsomes. Liver cells were obtained from Amphiuma, a type of salamander, and Claude found that after high-speed centrifugation and differential staining he was able to separate cell components, with the nucleus and mitochondria in one layer and the microsomes in a different layer. Identification of the components was aided by another of Claude’s innovations: the use of quantitative assays, or “biochemical mapping” as he called it, in which enzymatic activity was monitored in the different layers. Using this procedure Claude and his associates were able to identify mitochondria. The presence of respiratory enzymes associated with mitochondria provided the first evidence for their role in energy production in the cell.

In the early 1940s the integration of electron microscopy with cell biology allowed scientists not only to observe macroscopic aspects of cell organelles, but to observe them at a microscopic level. By 1945 Claude, along with colleague Keith Porter, was able to produce the first electron microscopic images of mitochondria and other cell components. Claude is considered one of the first researchers to study cells with an electron microscope.

The research portion of Claude’s career was largely completed by the late 1940s. He was offered a position at the Jules Bordet Institute at the University of Brussels, which he joined in 1950. He remained associated with the university until his retirement in 1971. During these years his work consisted of further analysis of cell components, leading to the identification of the Golgi bodies as sites of protein modification as well as their origin as part of the membrane system of endoplasmic reticulum. Though ostensibly retired, Claude accepted one more academic position as a professor at the Catholic University of Louvain-la-Neuve, where he maintained his interest in the Golgi bodies. In 1974 he was awarded the Nobel Prize in Physiology or Medicine for his work in isolating and identifying cellular components. Claude died at age eighty-four in Brussels.

Impact

The problems Claude faced during the early years of his work were highly challenging. Laboratory procedures and equipment routinely found in any modern biological laboratory were largely nonexistent. Any centrifuges that did exist were limited in their potential and were often unsafe. Nor did Claude have colleagues with whom he could consult when dealing with such problems; there were few scientists engaged in similar types of work. The application of cell fractionation itself was also questioned, as the prevailing belief was that cellular processes could only be understood within the whole cell.

Claude’s personal study of cell fractionation was largely completed by the mid-1940s. However his colleagues and students continued the work of analyzing the components under his guidance, while Claude himself began applying the new technique of electron microscopy in his work. As a prime example, during the early 1940s Claude had isolated a “large granule” fraction through high-speed centrifugation of cytoplasmic components. The granules were shown to exhibit a significant proportion of activity associated with respiratory enzymes. By 1947 Claude’s colleagues, in particular his corecipient of the Nobel Prize, George Palade, had proven that the granules Claude had isolated were the mitochondria of the cell.

The long-term impact resulting from Claude’s work lay not in his immediate discoveries but in the applications of his work in the next generation of cell biologists. Palade was instrumental in explaining the role played by Claude’s microsomes—ribosomes—in the synthesis of proteins. Palade convinced his own students to study the role played by the endoplasmic reticulum, the internal membrane structures first observed by Claude, in the modification and transport of proteins.

Bibliography

Alberts, Bruce, et al. Essential Cell Biology. New York: Garland Science, 2009. Print. Description of structure and functions of cell components. While Claude is not highlighted, the material represents the culmination of his discoveries.

Harris, Henry. The Birth of the Cell. New Haven: Yale UP, 1999. Print. History of cell biology. While Claude’s work was far in the future, Harris’s description of the origin of cell theory and the discovery of cell components provides an understanding of the early concept of the subject.

Karp, Gerald. Cell and Molecular Biology: Concepts and Experiments. Hoboken: Wiley, 2010. Print. Summarizes information about cellular components, along with details on their isolation and characterization. Claude’s techniques and contributions are briefly described.