Lancefield, Rebecca Craighill (1895-1981)
Lancefield, Rebecca Craighill (1895-1981)
Rebecca Craighill Lancefield is best-known throughout the scientific world for the system she developed to classify the bacteria Streptococcus. Her colleagues called her laboratory at the Rockefeller Institute for Medical Research (now Rockefeller University) "the Scotland Yard of streptococcal mysteries." During a research career that spanned six decades, Lancefield meticulously identified over fifty types of this bacteria. She used her knowledge of this large, diverse bacterial family to learn about pathogenesis and immunity of its afflictions, ranging from sore throats, rheumatic fever and scarlet fever, to heart and kidney disease. The Lancefield system remains a key to the medical understanding of streptococcal diseases.
Born Rebecca Craighill on January 5, 1895, in Fort Wadsworth on Staten Island in New York, she was the third of six daughters. Her mother, Mary Montague Byram, married William Edward Craighill, a career army officer in the Army Corps of Engineers who had graduated from West Point. Lancefield received a bachelor's degree in 1916 from Wellesley College, after changing her major from English to zoology. Two years later, she earned a master's degree from Columbia University, where she pursued bacteriology in the laboratory of Hans Zinsser. Immediately upon graduating from Columbia, she formed two lifelong partnerships. She married Donald Lancefield, who had been a classmate of hers in a genetics class. She was also hired by the Rockefeller Institute to help bacteriologists Oswald Avery and Alphonse Dochez, whose expertise on Pneumococcus was then being applied to a different bacterium. This was during World War I, and the project at Rockefeller was to discover whether distinct types of Streptococci could be isolated from soldiers in a Texas epidemic so that a serum might be produced to prevent infection. The scientists employed the same serological techniques that Avery had used to distinguish types of Pneumococcus. Within a year, Avery, Dochez, and Lancefield had published a major report which described four types of Streptococcus. This was Lancefield's first paper.
Lancefield and her husband took a short hiatus to teach in his home state at the University of Oregon, then returned to New York. Lancefield worked simultaneously on a Ph.D. at Columbia and on rheumatic fever studies at the Rockefeller Institute in the laboratory of Homer Swift, and her husband joined the Columbia University faculty in biology. Before World War I, physicians had suspected that Streptococcus caused rheumatic fever. But scientists, including Swift, had not been able to recover a specific organism from patients. Nor could they reproduce the disease in animals using patient cultures. Lancefield's first project with Swift, which was also her doctoral work, showed that the alpha-hemolytic class of Streptococcus, also called green or viridans, was not the cause of rheumatic fever.
As a result of her work with Swift, Lancefield decided that a more basic approach to rheumatic fever was needed. She began sorting out types among the disease-causing class, the beta-hemolytic streptococci . She used serological techniques while continuing to benefit from Avery's advice. Her major tool for classifying the bacteria was the precipitin test. This involved mixing soluble type-specific antigens, or substances used to stimulate immune responses, with antisera (types of serum containing antibodies) to give visible precipitates. Precipitates are the separations of a substance, in this case bacteria, from liquid in a solution, the serum, in order to make it possible to study the bacteria on its own.
Lancefield soon recovered two surface antigens from these streptococci. One was a polysaccharide, or carbohydrate, called the C substance. This complex sugar molecule is a major component of the cell wall in all streptococci. She could further subdivide its dissimilar compositions into groups and she designated the groups by the letters A through O. The most common species causing human disease, Streptococcus pyogenes, were placed in group A. Among the group A streptococci, Lancefield found another antigen and determined it was a protein, called M for its matt appearance in colony formations. Because of differences in M protein composition, Lancefield was able to subdivide group A streptococci into types. During her career, she identified over fifty types, and since her death in 1981, bacteriologists have identified thirty more.
Lancefield's classification converged with another typing system devised by Frederick Griffith in England. His typing was based on a slide agglutination method, in which the bacteria in the serum collect into clumps when an antibody is introduced. For five years the two scientists exchanged samples and information across the Atlantic Ocean, verifying each other's types, until Griffith's tragic death during the bombing of London in 1940. Ultimately, Lancefield's system, based on the M types, was chosen as the standard for classifying group A streptococci.
In further studies on the M protein, Lancefield revealed this antigen is responsible for the bacteria's virulence because it inhibits phagocytosis , thus keeping the white blood cells from engulfing the streptococci. This finding came as a surprise, because Avery had discovered that virulence in the Pneumococcus was due to a polysaccharide, not a protein. Lancefield went on to show the M antigen is also the one that elicits protective immune reactions.
Lancefield continued to group and type strep organisms sent from laboratories around the world. Until the end of her life her painstaking investigations helped unravel the complexity and diversity of these bacteria. Her thoroughness was a significant factor in her small but substantial bibliography of nearly sixty papers.
Once her system of classification was in place, however, Lancefield returned to her original quest to elucidate connections between the bacteria's constituents and the baffling nature of streptococcal diseases. She found that a single serotype of group A can cause a variety of streptococcal diseases. This evidence reversed a long-standing assumption that every disease must be caused by a specific microbe. Also, because the M protein is type-specific, she found that acquired immunity to one group A serotype could not protect against infections caused by others in group A.
From her laboratory at Rockefeller Hospital, Lancefield could follow patient records for very long periods. She conducted a study that determined that once immunity is acquired to a serotype, it can last up to thirty years. This particular study revealed the unusual finding that high titers, or concentrations, of antibody persist in the absence of antigen. In the case of rheumatic fever, Lancefield illustrated how someone can suffer recurrent attacks, because each one is caused by a different serotype.
In other studies, Lancefield focused on antigens. She and Gertrude Perlmann purified the M protein in the 1950s. Twenty years later she developed a more conservative test for typing it and continued characterizing other group A protein antigens designated T and R. Ten years after her official retirement, she made a vital contribution on the group B streptococci. She clarified the role of their polysaccharides in virulence and showed how protein antigens on their surface also played a protective role. During the 1970s, an increasingly high-rate of infants were born with group B meningitis , and her work laid the basis for the medical response to this problem.
During World War II, Lancefield had performed special duties on the Streptococcal Diseases Commission of the Armed Forces Epidemiological Board. Her task involved identifying strains and providing antisera for epidemics of scarlet and rheumatic fever among soldiers in military camps. After the commission dissolved, her colleagues in the "Strep Club" created the Lancefield Society in 1977, which continues to hold regular international meetings on advances in streptococcal research.
An associate member at Rockefeller when Maclyn McCarty took over Swift's laboratory in 1946, Lancefield became a full member and professor in 1958, and emeritus professor in 1965. While her career and achievements took place in a field dominated by men, Lewis Wannamaker in American Society for Microbiology News quotes Lancefield as being "annoyed by any special feeling about women in science." Nevertheless, most recognition for Lancefield came near her retirement. In 1961, she was the first woman elected president of the American Association of Immunologists, and in 1970, she was one of few women elected to the National Academy of Sciences. Other honors included the T. Duckett Jones Memorial Award in 1960, the American Heart Association Achievement Award in 1964, the New York Academy of Medicine Medal in 1973, and honorary degrees from Rockefeller University in 1973 and Wellesley College in 1976.
In addition to her career as a scientist, Lancefield had one daughter. Lancefield was devoted to research and preferred not to go on lecture tours or attend scientific meetings. Rockefeller's laboratories were not air-conditioned and her main diversion was leaving them during the summer and spending the entire season in Woods Hole, Massachusetts. There she enjoyed tennis and swimming with her family, which eventually included two grandsons. Official retirement did not change her lifestyle. She drove to her Rockefeller laboratory from her home in Douglaston, Long Island, every working day until she broke her hip in November 1980. She died of complications from this injury on March 3, 1981, at the age of eighty-six.
The pathogenesis of rheumatic fever still eludes scientists, and antibiotics have not eliminated streptococcal diseases. Yet the legacy of Lancefield's system and its fundamental links to disease remain and a vaccine against several group A streptococci is being developed in her former laboratory at Rockefeller University by Vincent A. Fischetti.
See also Bacteria and bacterial infection; Streptococci and streptococcal infections
Lancefield, Rebecca Craighill
LANCEFIELD, REBECCA CRAIGHILL
Rebecca Craighill was born at Fort wadsworth in New york City, where her father, William E. Craighill, was stationed as a colonel in the U.S. Army Engineering Corps. Her mother, Mary Wortly Montague Byram, a native of Mississippi, had met Craighill through her brother, who was his classmate at West point. After a somewhat peripatetic early life as the daughter of a Regular Army officer. Rebecca attended Wellesley College, graduating in 1916. Her graduate training was an integral part of the development of her scientific career. In 1918, just after receiving a master’s degree from Columbia University, she married Donald E. Lancefield, a fellow graduate student in biology who later became a professor of biology at Queens College. They had one daughter, Jane.
Essentially all of Rebecca Lancefield’s scientific research, extending over a period of some sixty years, dealt with a single large group of pathogenic bacteria, the streptococci. Her contributions form the basis for the present state of knowledge of this field. She brought order to the classification of this diverse group of organisms, clarified much of their basic biology, and provided explanations for their disease-producing capacity. This work had its beginning in 1918, shortly after she received her M. A., when she obtained a position as a technician at the Rockefeller Institute for Medical Research. She was assigned to the laboratory of Oswald T. Avery and Alphonse R. Dochez, who were studying a large collection of hemolytic streptococci that had been isolated during serious epidemics at military installations in 1917. It was not known at that time whether a single strain was involved or whether there were many different types of virulent streptococci, as had been shown to occur in the pneumococci. It was Lancefield’s task to sort out these strains serologically and determine their degree of diversity. Within a year she identified four distinct serological types that served to classify 70 percent of the strains studied. The paper describing this work marks the beginning of modern streptococcal biology.
Lancefield returned to graduate school in 1919 and later spent a year at the University of Oregon, where both she and Donald taught. She returned to the Rockefeller Institute in 1922, an affiliation that continued until her death. Her new assignment was in the laboratory of Homer F. Swift, which was concerned with streptococcal infections and rheumatic fever. At the outset her work dealt with a group of organisms known as “green” (viridans) streptococci; this research provided the dissertation for her Ph.D. from Columbia, which she received in 1925.
Turning her attention again to the hemolytic streptococci. Lancefield made rapid strides in the next few years. Two different antigens were identified and isolated from the organisms in soluble form: the first was type-specific and responsible for the distinctions between different strains that she had first observed in 1919; the other was more generally distributed and was present in all of her strains from cases of human disease. Lancefield determined that the type-specific antigen was a protein, which she called M-protein. Subsequently she demonstrated that it was the principal virulence factor of streptococci and that immunity to streptococcal infection was directed primarily to M-protein (and thus was type-specific). This proved of great importance in the understanding of the epidemiology of streptococcal disease, since there are now known to exist several dozen different types, each with a different M-protein.
Lancefield showed that the other antigen was carbohydrate in nature and that this kind of antigen could be used to divide streptococci into subgroups. Thus, while the strains isolated from strep throat and other human diseases (designated group A) all had the same carbohydrate antigen, a group of strains from bovine mastitis had a quite different carbohydrate, and those from horses with strangles a third. Still other groups were encountered, and Lancefield was able to sort out the many different varieties of hemolytic streptococci that exist in nature by means of serological analysis of the different antigens of this class.
Much of Lancefield’s subsequent work dealt with group A streptococci because of their role in human diseases, particularly rheumatic fever and glomerulonephritis. She clarified the nature and biological properties of the antigens found previously, described new protein antigens, and explored the implications of all of them for the production of disease, Her work was not limited to this single group, however, and she defined the properties of group B streptococci, originally thought to be primarily of bovine origin but now of concern because of neonatal infections in humans. As in group A, she found several different serological types, but in this case the typespecific antigens were capsular polysaccharides rather than proteins.
Lancefield’s contributions have been widely recognized, and the varieties of streptococci are known throughout the world as the Lancefield groups and types. She received many honors, but the one that best reflects the esteem of her colleagues came when the professional organization concerned with streptococci in this country changed its name to the Lancefield Society in 1977. The international society in this field made the same change in 1981, shortly after her death.
I. Original Works. Nearly all of Rebecca Lancefield’s research was published in Journal of Experimental Medicine between 1919 and 1979 (35 papers). Listed here are her initial paper and reviews that will serve as reference to her most important studies: “Studies on the Biology of Streptococcus, I. Antigenic Relationships Between Strains of Streptococcus hemolyticus,” in Journal of Experimental Medicine, 30 (1919), 179–213, with A. R. Dochez and O. T. Avery; “Specific Relationship of Cell Composition to Biological Activity of Hemolytic Streptococci,” in Harvey Lectures, 36 (1941), 251–290; “Current Knowledge of Type-specific M Antigens of Group A Streptococci,” in Journal of Immunology, 89 (1962), 307–313; and “Multiple Mouse Protective Antibodies Directed Against group B Streptococci: Special Reference to An-tibodies Effective Against Protein Antigens,” in Journalof Experimental Medicine, 142 (1975), 165–179, with Maclyn McCarty and William N. Everly.