Biographical Feature: Rebecca Lancefield, Ph.D.

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What microbiologist or student of the streptococci does not recognize the name Rebecca Lancefield? We are all familiar with the classification of the beta-hemolytic streptococci that bears her name and aptly so, as she painstakingly developed the system of separating the human strains (group A beta-hemolytic Streptococcus) from those believed to cause disease primarily in animals. A lover of biology and a careful scientist, she contributed much more to our knowledge of the pathogenesis of the streptococci, beyond this typing system, over the span of her remarkable 60-year career. Her work laid the foundation for subsequent studies of the epidemiology, immunology, and pathogenesis of streptococcal infections. Both bacteriologists and immunologists claim her as their Streptococcus “pioneer,” and both groups ultimately bestowed her with well-deserved honors throughout her career.

Rebecca Lancefield, circa late 1920s. (Reprinted with permission of The Rockefeller Archive Center.)

Rebecca Lancefield was born Rebecca Craighill in Fort Wadsworth, Staten Island, NY, on 5 January 1895 to parents William E. Craighill, a colonel in the U.S. Army Corps of Engineers, and Mary Wortley Byram, a descendant of Lady Mary Wortley Montagu, who championed vaccination against smallpox (1–3). In addition, her mother was a champion of women’s education and instilled in her daughters a devotion to academic advancement (4). One of Rebecca’s sisters, Margaret, became an accomplished physician (4, 5). Rebecca attended Wellesley College in Massachusetts, majoring in liberal arts (French and English literature) upon entry in 1912. However, thanks to her roommate, who was a zoology major, Rebecca became interested in the biological sciences, and she graduated in 1916 with a bachelor’s degree in zoology. During her time at Wellesley, her father died. After graduation, to assist in the support of her five younger sisters, she took a position teaching math and science at a high school in Vermont, an avocation to which she did not aspire. However, she accepted a scholarship offered to the daughters of deceased army and navy officers to attend Teachers’ College at Columbia University (2). She petitioned the administrators at Teachers’ College to allow her to pursue an M.A. course in bacteriology in Dr. H. Zinsser’s Department of Bacteriology at Columbia’s College of Physicians and Surgeons. They agreed, and in 1918, the same year that she married Donald E. Lancefield, a fellow graduate student in genetics, she received her master’s degree from Columbia University (1–5).

There are different accounts of where Dr. Zinsser was when Lancefield entered his department, but he was absent during the time that she was in his laboratory (1, 2). She studied and serotyped pneumococci recovered from patients in the laboratory at the Presbyterian Hospital and attended numerous lectures on these organisms, but her master’s thesis was on Staphylococcus. One source states that Professor F. P. Gay at Columbia mentored Rebecca, and after her graduation, he mentioned to her that Oswald T. Avery and Alphonse R. Dochez, well-recognized pneumococcal researchers at the Rockefeller Institute for Medical Research, were in need of a laboratory technician to assist with their work in studying streptococcal infections at military bases (1). As an aside, Dr. Avery, along with Colin MacLeod and Maclyn McCarty, is credited with the discovery of DNA as the genetic material, a consequence of their tremendous investigative pneumococcal work (4). Rebecca applied for the position, and after successful interviews with both scientists, she was quickly hired. Her acceptance of that position was a turning point in her career.

It is important to put into context what was happening globally in 1918 and to emphasize that this was the preantibiotic era and few vaccines were available. The United States had entered the First World War, and troops were becoming ill with influenza and measles and, at some military bases, with secondary, serious streptococcal infections. Millions of children suffered from debilitating heart disease from rheumatic and scarlet fever, and the precise etiologies of these conditions were unknown. The U.S. Government asked Drs. Avery and Dochez, pneumococcus researchers, to study the secondary streptococcal infections among troops at camps in Texas. One of the unanswered questions was whether the hemolytic streptococci also had distinct serotypes, as Drs. Avery and Dochez had determined for the pneumococci, or whether just a single strain was responsible for the outbreaks (2). They sent 125 samples collected from ill soldiers to the Avery laboratory, and within a year, the three investigators classified the majority of the isolates. The techniques used were agglutination reactions and the development of specific antisera that prevented disease in mice (2). At that time, four distinct serotypes were identified, and for her significant role in the project, Mrs. Lancefield was offered coauthorship with Drs. Avery and Dochez on the paper entitled “Studies on the Biology of Streptococcus: I. Antigenic Relationships between Strains of Streptococcus haemolyticus” (6). It was very rare for a research technician to be offered coauthorship on a manuscript during that era (2, 4).

After the grant was completed, Lancefield was hired to work as a technician in the genetics laboratory of Dr. Charles Metz at Columbia University, where she worked on Drosophila genetics. In 1921, she and her husband moved to Oregon, as Donald was offered a teaching position in the Department of Zoology at the University of Oregon. Rebecca taught bacteriology during their very brief stay of 1 year, and they returned to New York when Donald was offered and accepted a position in the Zoology Department of Columbia. Rebecca aspired to pursue her Ph.D. in bacteriology under Dr. Zinsser at Columbia. However, as Professor Zinsser did not believe that women should work in research laboratories, she once again found herself at Rockefeller University in the laboratory of Dr. Homer Swift, a physician-researcher who was launching a new project on rheumatic fever (4). Working at two institutions simultaneously required her to carry racks of test tubes between labs (4). The pathogen responsible for rheumatic fever was still unknown, and Dr. Swift proposed that alpha-hemolytic streptococci, specifically viridans streptococci, were the cause (4, 5). Two years later, after significant, painstaking, and often frustrating work, Lancefield unequivocally determined that these organisms were not implicated in rheumatic fever (7, 8). She received her Ph.D. for this work from Columbia University in 1925.

After receiving her doctorate, Rebecca Lancefield, in an effort to better understand streptococcal pathogenesis, turned her attention back to the hemolytic streptococci. She and Drs. Dochez and Avery had succeeded in identifying four serological types from their Texas outbreak work, but very little was known about the biological properties that contributed to the virulence of these bacteria and the broad range of infections, from pharyngitis to rheumatic fever, caused by these streptococcal organisms. Rebecca revived the 125 streptococcal cultures from the Texas military camp outbreaks, and using the techniques she had learned in Avery’s lab, she began to classify the beta-hemolytic streptococci. Her goal was to use the typing system to further identify antigens that might contribute to pathogenesis. Based upon the pneumococcal work, she expected these antigens to be complex carbohydrates. After many experiments, she isolated two soluble surface antigens—one was type specific for the strains from the 1918 outbreak, and the second was species specific, that is, common to all streptococci. To her surprise, the type-specific antigen was a protein that she called M-protein (referring to the growth of the matt colonies that they formed). The species-specific antigen was a carbohydrate that she called C-carbohydrate. As she collected and tested a variety of human and animal isolates from around the country, it became clear that the species-specific antigen, or C-carbohydrate, was group specific, and this group distinction formed her classification system. This work resulted in five publications (2, 9–13). Lancefield designated group A for the highly virulent human pathogens and group B for bovine streptococcal infections (14, 15). Throughout the 1930s, Lancefield and others refined the classification system, such that by 1940, groups A through H, L, and M had been characterized (2).

Other groundbreaking work on the group A streptococci followed, and Rebecca determined that she could classify this group into more than 50 types based upon variability in M-proteins. According to Dr. Vincent Fischetti, professor and head at the Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, Rebecca was up to M type 61 at the time of her death. He comments, “She was extremely careful and methodical in everything she did. All of the serological M types that she identified were subsequently verified by emm (genetic) typing, a true testament to her meticulous approach.” Today, there are more than 200 serotypes. She also showed that M-protein inhibited white blood cell phagocytosis and that immunity to one M-protein serotype did not prevent infection caused by other serotypes—a breakthrough that explained the recurrence of streptococcal infections such as strep throat.

When it became apparent that group B streptococci could cause infection particularly in neonates, Lancefield turned her attention to this group. Interestingly, she discovered that group B streptococci lacked M-protein and that surface polysaccharides were important for virulence (5). Soon thereafter, World War II began, and Rebecca served on the Commission on Streptococcal and Staphylococcal Diseases of the Armed Forces Epidemiological Board (2, 4, 5). This work informed additional studies on the epidemiology of streptococcal outbreaks, ultimately leading to recommendations for less crowded military barracks (2). She was a huge resource for global queries and accepted isolates from locations within the United States and abroad for streptococcal typing. Her laboratory at Rockefeller University became known as “the Scotland Yard of streptococcal mysteries” (5). To this day, the Lancefield collection of strains, consisting of over 6,000 isolates, some from the original Texas outbreaks, resides at Rockefeller University in the Bacteriology and Immunology Department (http://lab.rockefeller.edu/fischetti/lanceindex).

Rebecca Lancefield enjoyed a long life, and she worked well into her 80s. Dr. Fischetti fondly recalls, “Mrs. L (as she was called by those who know her) would come in around noon to avoid traffic (she drove about 15 miles from Douglaston, NY) and work the rest of that day. She would then stay overnight at the Rockefeller, in a room at the University Hospital that was arranged for her, and work the next day, after which she would drive home.”

During her long career, Dr. Lancefield ascended through the academic ranks. In 1946, she was promoted to associate member at Rockefeller Institute, and 12 years later, she was promoted to full member and professor. She collaborated with Maclyn McCarty, a renowned immunologist, and mentored Emil Gotschlich, both of whom received the Lasker award, Dr. McCarty in 1994 for special achievement in medical science and Dr. Gotschlich in 1978 for clinical medical research (5). Professor McCarty in his short biography of Rebecca Lancefield notes that he was grateful for their collaboration and for the opportunity to observe her work style and ethics. Speaking about her appreciation for the complexity of the work she was performing, he comments in his biographical memoir, “Such careful investigations, however, prevented her from drawing misleading and oversimplistic conclusions, and her meticulous approach is responsible, I believe, for the great durability and reproducibility of her published findings” (2), echoing the above comments by Dr. Fischetti.

Several writers comment upon Dr. Lancefield’s warm personality (2, 4, 5). She supported young scientists as a “caring and generous mentor” in both their research endeavors and their organization of departmental social and extracurricular events (4). One person noted, “She never missed a party…” (4, 5, 16). A nonscientific recognition among graduate students was apparently that of Rebecca’s family eggnog recipe, which spurred a traditional eggnog party around the holidays within the department (2, 4). The recipe was published on Science Friday in 2008. Eggnog aficionados can find it at https://sciencefriday.tumblr.com/post/36824999206/dr-rebecca-lancefields-eggnog-recipe. She also expressed concern for and was supportive of the personnel and students in her laboratory, offering advice and assistance, even for personal problems. Rebecca took time to relax with her family in Woods Hole, MA, every summer to escape the humidity of New York. There, she enjoyed tennis and swimming, the latter well into her 8th decade (2).

In 1965, Rebecca became emeritus professor. During her long career, she received many honors which many believed were long overdue. She was elected president of the Society of American Bacteriologists (now the American Society for Microbiology) in 1943. She was presented with the T. Duckett Jones Memorial Award by the Helen Hay Whitney Foundation in 1960. In recognition of her outstanding contributions to immunology, including the central role of M-protein in immunity to group A Streptococcus, in 1961, her peers elected her to serve as president of the American Association of Immunologists. She was the first woman elected to this office. The American Heart Association gave her its 1964 achievement award. Dr. Lancefield was elected as a member of the National Academy of Sciences in 1970, and in 1973, she was presented with the New York Academy of Medicine Medal for her contributions to the knowledge of our understanding of the streptococci. Rockefeller University gave her the honorary Doctor of Science, its highest recognition, in 1973, and Wellesley College also awarded her an honorary degree in 1976 on the 60th anniversary of her graduation and the 100th anniversary of the college (1–5). In 1977, The Lancefield Society was created to hold annual meetings in the United States to discuss streptococcal research—a testimony to the esteem held by other scientists. Her reputation extended to Europe, where she was accorded honorary status in the Pathological Society of Great Britain and in the Royal College of Pathologists in Ireland. Although she was truly a “pioneering woman in science,” she preferred that her honors and recognition refrain from references to her gender (2).

Rebecca was not only a superb research scientist and a warm and respected colleague but also devoted to her husband and daughter, Jane. Jane recalled her mother’s “extraordinary energy” and devotion to science, and she also commented that her father, Donald, supported Rebecca and shared home duties, including cooking meals (4). Both parents shared a love of science and were devoted partners. Rebecca continued to work in her laboratory until November 1980, when she suffered a broken hip, and she cochaired the Laboratory of Bacteriology and Immunology with Dr. McCarty until that time as well. Unfortunately, she died on 3 March 1981, at the age of 86, due to complications from the hip fracture. She was survived by her husband, Donald, her daughter, Jane Maddox Hersey, and two grandsons, Donald and James (2, 4).

Dr. Lancefield’s story is inspiring to all microbiologists, because not only did she follow her science, but in so doing, she rose from research technician to full professor and celebrated investigator. Perhaps no one has summarized the essence of Rebecca Lancefield better than Maclyn McCarty, M.D., who wrote, on the presentation of the New York Academy of Medicine Medal to her in 1973, “Dr. Lancefield’s career is an impressive illustration of the fruits of persistent and systematic investigation in depth of the biology of a pathogenic microorganism” (3). For that distinction, researchers, clinicians, and innumerable patients have benefited.