Rebecca Craighill Lancefield Biography (1895-1981)
Rebecca Craighill Lancefield is known throughout the world for the system shedeveloped to classify the bacterium streptococcus. Her colleagues called herlaboratory at the Rockefeller Institute for Medical Research (now Rockefeller University) "the Scotland Yard of streptococcal mysteries." During a research career that spanned six decades, she meticulously identified over fifty types of this bacteria. She used her knowledge of this large, diverse bacterialfamily to learn about pathogenesis and immunity of its afflictions, rangingfrom sore throats, rheumatic fever and scarlet fever toheart and kidney disease. The Lancefield system remains a key to the medicalunderstanding of streptococcal diseases.
Born Rebecca Craighill on January 5, 1895, in Fort Wadsworth on Staten Islandin New York on January 5, 1895, 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'sdegree from Columbia University, where she pursued bacteriology in the laboratory of Hans Zinsser. Immediately on graduating from Columbia, she formed two lifelong partnerships. She married Donald Lancefield, who had been aclassmate of hers in a genetics class. And she was 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 whetherdistinct 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 pneumococci. Within a year, Avery, Dochez, and Lancefield hadpublished a major report which described four types of streptococci. This was Lancefield's first paper.
Lancefield and her husband took a short hiatus to teach in his home state atthe 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 a streptococcus caused rheumatic fever. But scientists, includingSwift, 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, wasnot 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. So she began sorting out types among thedisease-causing class, the beta-hemolytic streptococci. She used serologicaltechniques 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 studythe 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. Amongthe group A streptococci, Lancefield found another antigen and determined itwas a protein, called M for its matt appearance in colony formations. Becauseof 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 collects 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 classifyinggroup 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 laboratoriesaround the world. Until the end of her life, her painstaking investigationshelped unravel the complexity and diversity of these bacteria. Lancefield's colleague Maclyn McCarty, told contributor Carol L. Moberg that Lancefield was"never satisfied with quick answers," and her success came from a determination to stick with scientific problems for a long time. Her thoroughness, he added, was a significant factor in her small but substantial bibliography of nearly sixty papers.
Once her system of classification was in place, however, Lancefield returnedto 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 belief that every disease must be caused bya 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 patientrecords for very long periods. She conducted a study which 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 rheumaticfever, 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 increasinglyhigh-rate of infants were being 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 taskinvolved identifying strains and providing antisera for epidemics of scarletfever 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 aboutwomen in science." In Profiles of Pioneer Women Scientists, ElizabethO'Hern cites Lancefield as saying that women "sometimes expect too much." 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 fromher 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. Her husband Donald died the following August.
The pathogenesis of rheumatic fever still eludes scientists, and antibioticshave 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.