Stanley, Wendell Meredith (1904-1971) (World of Microbiology and Immunology)
Wendell Meredith Stanley was a biochemist who was the first to isolate, purify, and characterize the crystalline form of a virus. During World War II, he led a team of scientists in developing a vaccine for viral influenza. His efforts have paved the way for understanding the molecular basis of heredity and formed the foundation for the new scientific field of molecular biology. For his work in crystallizing the tobacco mosaic virus, Stanley shared the 1946 Nobel Prize in chemistry with John Howard Northrop and James B. Sumner.
Stanley was born in the small community of Ridgeville, Indiana. His parents, James and Claire Plessinger Stanley, were publishers of a local newspaper. As a boy, Stanley helped the business by collecting news, setting type, and delivering papers. After graduating from high school he enrolled in Earlham College, a liberal arts school in Richmond, Indiana, where he majored in chemistry and mathematics. He played football as an undergraduate, and in his senior year, he became team captain and was chosen to play end on the Indiana All-State team. In June of 1926, Stanley graduated with a Bachelor of Science degree. His ambition was to become a football coach, but the course of his life was changed forever when an Earlham chemistry professor invited him on a trip to Illinois State University. Here, he was introduced to Roger Adams, an organic chemist, who inspired him to seek a career in chemical research. Stanley applied and was accepted as a graduate assistant in the fall of 1926.
In graduate school, Stanley worked under Adams, and his first project involved finding the stereochemical characteristics of biphenyl, a molecule containing carbon and hydrogen atoms. His second assignment was more practical; Adams was interested in finding chemicals to treat leprosy, and Stanley set out to prepare and purify compounds that would destroy the disease-causing pathogen. Stanley received his master's degree in 1927 and two years later was awarded his Ph.D. In the summer of 1930, he was awarded a National Research Council Fellowship to do postdoctoral studies with Heinrich Wieland at the University of Munich in Germany. Under Wieland's tutelage, Stanley extended his knowledge of experimental biochemistry by characterizing the properties of some yeast compounds.
Stanley returned to the United States in 1931 to accept the post of research assistant at the Rockefeller Institute in New York City. Stanley was assigned to work with W. J. V. Osterhout, who was studying how living cells absorb potassium ions from seawater. Stanley was asked to find a suitable chemical model that would simulate how a marine plant called Valonia functions. Stanley discovered a way of using a water-insoluble solution sandwiched between two layers of water to model the way the plant exchanged ions with its environment. The work on Valonia served to extend Stanley's knowledge of biophysical systems, and it introduced him to current problems in biological chemistry.
In 1932, Stanley moved to the Rockefeller Institute's Division of Plant Pathology in Princeton, New Jersey. He was primarily interested in studying viruses. Viruses were known to cause diseases in plants and animals, but little was known about how they functioned. Stanley's assignment was to characterize viruses and determine their composition and structure.
Stanley began work on a virus that had long been associated with the field of virology. In 1892, D. Ivanovsky, a Russian scientist, had studied tobacco mosaic disease, in which infected tobacco plants develop a characteristic mosaic pattern of dark and light spots. He found that the tobacco plant juice retained its ability to cause infection even after it was passed through a filter. Six years later M. Beijerinck, a Dutch scientist, realized the significance of Ivanovsky's discovery: the filtration technique used by Ivanovsky would have filtered out all known bacteria, and the fact that the filtered juice remained infectious must have meant that something smaller than a bacterium and invisible to the ordinary light microscope was responsible for the disease. Beijerinck concluded that tobacco mosaic disease was caused by a previously undiscovered type of infective agent, a virus.
Stanley was aware of recent techniques used to precipitate the tobacco mosaic virus (TMV) with common chemicals. These results led him to believe that the virus might be a protein susceptible to the reagents used in protein chemistry. He set out to isolate, purify, and concentrate the tobacco mosaic virus. He planted Turkish tobacco plants, and when the plants were about 6 in (15 cm) tall, he rubbed the leaves with a swab of linen dipped in TMV solution. After a few days, the heavily infected plants were chopped and frozen. Later, he ground and mashed the frozen plants to obtain a thick, dark liquid. He then subjected the TMV liquid to various enzymes and found that some would inactivate the virus and concluded that TMV must be a protein or something similar. After exposing the liquid to more than 100 different chemicals, Stanley determined that the virus was inactivated by the same chemicals that typically inactivated proteins, and this suggested to him, as well as others, that TMV was protein-like in nature.
Stanley then turned his attention to obtaining a pure sample of the virus. He decanted, filtered, precipitated, and evaporated the tobacco juice many times. With each chemical operation, the juice became more clear and the solution more infectious. The result of two-and-one-half years of work was a clear concentrated solution of TMV that began to form into crystals when stirred. Stanley filtered and collected the tiny, white crystals and discovered that they retained their ability to produce the characteristic lesions of tobacco mosaic disease.
After successfully crystallizing TMV, Stanley's work turned toward characterizing its properties. In 1936, two English scientists at Cambridge University confirmed Stanley's work by isolating TMV crystals. They discovered that the virus consisted of 94% protein and 6% nucleic acid, and they concluded that TMV was a nucleoprotein. Stanley was skeptical at first. Later studies, however, showed that the virus became inactivated upon removal of the nucleic acid, and this work convinced him that TMV was indeed a nucleoprotein. In addition to chemical evidence, the first electron microscope pictures of TMV were produced by researchers in Germany. The pictures showed the crystals to have a distinct rod-like shape. For his work in crystallizing the tobacco mosaic virus, Stanley shared the 1946 Nobel prize in chemistry with John Howard Northrop and James Sumner.
During World War II, Stanley was asked to participate in efforts to prevent viral diseases, and he joined the Office of Scientific Research and Development in Washington D.C. Here, he worked on the problem of finding a vaccine effective against viral influenza. Such a substance would change the virus so that the body's immune system could build up defenses without causing the disease. Using fertilized hen eggs as a source, he proceeded to grow, isolate, and purify the virus. After many attempts, he discovered that formaldehyde, the chemical used as a biological preservative, would inactivate the virus but still induce the body to produce antibodies. The first flu vaccine was tested and found to be remarkably effective against viral influenza. For his work in developing large-scale methods of preparing vaccines, he was awarded the Presidential Certificate of Merit in 1948.
In 1948, Stanley moved to the University of California in Berkeley, where he became director of a new virology laboratory and chair of the department of biochemistry. In five years, Stanley assembled an impressive team of scientists and technicians who reopened the study of plant viruses and began an intensive effort to characterize large, biologically important molecules. In 1955 Heinz Fraenkel-Conrat, a protein chemist, and R. C. Williams, an electron microscopist, took TMV apart and reassembled the viral RNA, thus proving that RNA was the infectious component. In addition, their work indicated that the protein component of TMV served only as a protective cover. Other workers in the virus laboratory succeeded in isolating and crystallizing the virus responsible for polio, and in 1960, Stanley led a group that determined the complete amino acid sequence of TMV protein. In the early 1960s, Stanley became interested in a possible link between viruses and cancer.
Stanley was an advocate of academic freedom. In the 1950s, when his university was embroiled in the politics of McCarthyism, members of the faculty were asked to sign oaths of loyalty to the United States. Although Stanley signed the oath of loyalty, he publicly defended those who chose not to, and his actions led to court decisions which eventually invalidated the requirement.
Stanley received many awards, including the Alder Prize from Harvard University in 1938, the Nichols Medal of the American Chemical Society in 1946, and the Scientific Achievement Award of the American Medical Association in 1966. He held honorary doctorates from many colleges and universities. He was a prolific author of more than 150 publications and he co-edited a three volume compendium entitled The Viruses. By lecturing, writing, and appearing on television he helped bring important scientific issues before the public. He served on many boards and commissions, including the National Institute of Health, the World Health Organization, and the National Cancer Institute.
Stanley married Marian Staples Jay on June 25, 1929. The two met at the University of Illinois, when they both were graduate students in chemistry. They co-authored a scientific paper together with Adams, which was published the same year they were married. The Stanleys had three daughters and one son. While attending a conference on biochemistry in Spain, Stanley died from a heart attack at the age of 66.
See also History of immunology; History of microbiology; Viral genetics; Viral vectors in gene therapy; Virology; Virus replication; Viruses and responses to viral infection