Wendell Stanley

American biochemist

• Born: August 16, 1904
• Birthplace: Ridgeville, Indiana
• Died: June 15, 1971
• Place of death: Salamanca, Spain

Stanley’s crystallization of the tobacco mosaic virus in the mid-1930’s illustrated the ability to purify viruses in large quantities for subsequent study and also demonstrated the protein nature of viruses.

Early Life

Wendell Stanley was born to James and Claire (Plessinger) Stanley, who were publishers of two small newspapers. James Stanley died in 1920, and the family moved to Richmond, Indiana, where Wendell attended the local high school. Following graduation from high school in 1922, Stanley enrolled in Earlham College in Richmond, majored in chemistry and mathematics, and graduated with a bachelor of science degree in 1926. His interests also extended to sports, and while at Earlham he was a member of the football team, was elected captain his senior year, and was selected for the Indiana All-State Team. After graduation, his initial interests remained in the area of sports, and Stanley had hopes of becoming a football coach.

Stanley moved on to the University of Illinois, earning a master of science degree in 1927 and a Ph.D. in chemistry in 1929. While at Illinois, Stanley met Professor Roger Adams, chair of the department of chemistry at the university, with whom Stanley developed an interest in chemistry’s application in medical research. Among Adams’s students at the time was Marian Staples Jay. Stanley and Jay married in 1929.

For the next two years Stanley worked as a research assistant with Adams at Illinois until accepting a position as a National Research Council Fellow in Munich, Germany. There he worked for a year with Heinrich Wieland, a 1927 Nobel laureate for his work with bile acids. In 1931, Stanley returned to the United States, where he became an assistant at the Rockefeller Institute in New York, working with cell physiologist W. J. Osterhout. The following year, Stanley was invited by Rockefeller scientist Simon Flexner to join his staff at the institute’s Department of Plant and Animal Pathology in Princeton, New Jersey. There he became an associate member in 1937 and a member in 1940.

Life’s Work

In the last decade of the nineteenth century, Dmitry Ivanovsky and Martinus Beijerinck observed that filtered cell-free extracts prepared from tobacco leaves exhibiting tobacco mosaic disease would transfer the disease to fresh tobacco leaves. The filtrate, called a contagium vivum fluidum (soluble living germ), contained a replicating substance of some sort, the nature of which was unclear. Subsequently, the agent was determined to be a specific entity, an agent now known as the tobacco mosaic virus, or TMV. The ability to grow and maintain the virus made it a useful tool for the study of virus infections, analogous to a growing number of such agents observed in animals.

When Stanley began the work that led to his Nobel Prize, the nature of viruses, other than observations that they had the ability to replicate, was unknown. The source of their genetic information was likewise unknown, and indeed would remain so well into the 1940’s. However, whether they were composed entirely of protein, or instead contained carbohydrate or lipid, also remained a mystery. In 1930, William Elford was able to size viruses, including TMV, by determining the size of a filter that would retain the agent. He concluded that virus particles had specific sizes, and that the sizes overlapped with both living and nonliving substances, making a clear definition of what constituted a virus even more confusing. At the time of Elford’s work, the technology of the electron microscope had not been developed to the extent that one could directly observe the structure of submicroscopic particles like viruses.

Stanley knew that some viruses, particularly TMV, could be grown in large quantities, purified and titrated, and used in chemical analyses. In a series of five papers published in 1934 and 1935 he outlined how proteolytic enzymes under different environmental conditions, including that of pH the acid content of the solution could inactivate crystalline TMV. He observed that inactivation occurred only under conditions in which the agent was initially infectious. Disruption of the virus resulted in a loss of infectivity. Furthermore, the virus could be precipitated and crystallized under conditions in which proteins in general could be precipitated, such as in the presence of ammonium sulfate. The chemical makeup of the crystal was shown to include amino acids, confirming the protein nature of TMV.

Scientists studying viruses concurrently with Stanley believed that Stanley’s work placed viruses in an area that overlapped the living world of bacteria and the nonliving world of organic molecules and crystals. The symmetrical nature of most viruses as either a helix or icosahedron (cuboidal) would not be known until the widespread application of the electron microscope.

While carrying out these studies, Stanley and colleagues in the field in 1937 also observed the presence of pentose nucleic acid in the particles, which are now known to be ribonucleic acid, or RNA. The significance of the discovery in 1937 was not realized, but what was recognized was Stanley’s conclusion that the TMV particle consisted of nucleoprotein. The ability of electron microscopes during these years to magnify the particle resulted in the observation that TMV existed as long thin rods.

Stanley’s subsequent work involved the study of the influenza virus, and he made contributions in the development of early influenza vaccines as a member of theU.S. Army Commission on Influenza during World War II. He also studied the chemical nature of sterols. It was around this time that Stanley became convinced that viruses may play a role in development of cancer. In recognition of his work in this area, he would be named president of the Tenth International Cancer Congress in 1970.

Stanley was awarded the Nobel Prize in Chemistry in 1946, primarily for his studies of the crystallization and the chemical structure of viruses. Among his many other prestigious awards was the American Association for Advancement of Science Prize (1937), the Nichols Medal (1946) and the Gibbs Medal (1947) from the American Chemical Society, and the Medal for Distinguished Work in Cancer Control by the American Cancer Society (1963). He also received numerous honorary doctorates from colleges and universities, including Harvard, Yale, Princeton, Illinois, and the University of Paris. He became a foreign associate member of the French Academy of Sciences of the Institute of France in 1970.

In 1948, Stanley left the Rockefeller Institute. From 1948 until his death in 1971, he was a professor of biochemistry at the University of California, Berkeley, as well as the director of the university’s laboratory on virus research, which he founded. Between 1948 and 1953, he served as chair of the Biochemistry Department and was known as the founder of Berkeley chemistry. In 1954, he was part of the team that crystallized the polio virus, marking the first time an animal virus was crystallized.

Stanley died after having a heart attack at a conference in Spain. He had been chairing a symposium at the time. He was survived by his wife, Marian; his son, Wendell Stanley, Jr., who followed in his father’s professional footsteps; and three daughters, Marjorie, Dorothy, and Janet.

Significance

When Stanley began his work, the nature of viruses was still largely unknown. By proving that one could crystallize viruses, he demonstrated that one could purify these agents in high concentrations, and that they consisted of specific organic material, mainly protein. The significance of his observation that TMV also contained pentose nucleic acid, or RNA, was missed at the time. The ability to purify viruses also meant that these agents could be studied in chemical laboratories using “standard” chemical procedures.

Whether viruses are actually alive, as conceived by vitalists active during Stanley’s work in the 1930’s, or consist merely of organic material no different in concept than chemical substances in general, is a question that remains unanswered with any certainty. Stanley’s ability to convey his ideas about viruses as straddling the two viewpoints was part of the legacy of his work.

Bibliography

Acheson, Nicholas. Fundamentals of Molecular Virology. Hoboken, N.J.: John Wiley & Sons, 2007. Includes a history of modern virology. Summarized the work of Stanley and others in the crystallization of viruses.

Brock, Thomas, ed. Milestones in Microbiology. Washington, D.C.: American Society for Microbiology Press, 1999. Collection of historic papers that defined the development of bacteriology-microbiology. Included is Stanley’s 1935 paper that reported the crystallization of TMV. Includes commentary by the editor.

Cann, Alan. Principles of Molecular Virology. 4th ed. New York: Elsevier-Academic Press, 2005. A concise discussion of the principles of virus structure and replication. Includes a chapter on the history of virology. While Stanley is not specifically noted, the significance of his work is highlighted.

Dimmock, N. J., A. J. Easton, and K. N. Leppard. Introduction to Modern Virology. 6th ed. Malden, Mass.: Blackwell, 2007. Molecular biology of viruses. Included is a chapter explaining the role of cellular (and viral) oncogenes in the regulation of cell reproduction. Definitions help clarify the material.

Knipe, D., et al. Fundamental Virology. 4th ed. Philadelphia: Lippincott Williams and Wilkins, 2001. Abridged version of a larger text. A history of the subject is part of the extensive coverage of viruses in general.