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Summer 1990 "Mrs. L." : [Dr. Rebecca Lancefield] Judith N. Schwartz

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Recommended Citation Schwartz, Judith N., ""Mrs. L." : [Dr. Rebecca Lancefield]" (1990). Rockefeller University Research Profiles. Book 35. http://digitalcommons.rockefeller.edu/research_profiles/35

This Article is brought to you for free and open access by the Campus Publications at Digital Commons @ RU. It has been accepted for inclusion in Rockefeller University Research Profiles by an authorized administrator of Digital Commons @ RU. For more information, please contact [email protected]. THE ROCKEFELLER UNIVERSITY RESEARCH PROJFILES Precipitin rack and hand lens used by Dr. Lancefield SUMMER 1990

"Mrs. L."

Her laboratory was called "the Scotland Yard ofstrepto­ coccal mysteries." In it, for more than sixty years, Rebecca Lancefield stalked a devious, multifarious adversary: the streptococcal bacteria. For those with access to modern medical care and antibiotics, a touch of"strep" may not seem a particularly serious threat. In 1918, when Rebecca Lancefield first came to The Rockefeller Institute for Medical Research (later The Rockefeller University), the diseases caused by Rebecca Lancefield, streptococcal infection, among them rheumatic fever, 1895-1981 scarlet fever, and acute nephritis, were common and dangerous ailments. Millions of people, mostly children, developed crippling heart disease in the wake ofrheumatic fever. Millions in Mrica, Asia, and Latin America still do. When she began her research no one knew how many kinds ofstreptococci existed, which ones were dangerous to man, or how they did their damage. The link between strep infection and rheumatic fever had been postulated but not proven. Her work provided the basis for answer­ ing those questions and for the development of effective diagnosis and treatment. The system she devised for Page 2

Electron classifYing the streptococcal bacteria that infect human micrograph of beings is considered the single most important contribu­ streptococcal tion that has been made to medical understanding of bacteria, magnified streptococcal disease. about 70)000 times. She started out as a technical assistant. She rose to Fuzz around the become a professor and co-leader of The Rockefeller bacteria is composed University'S laboratory ofbacteriology and immunology, ofMprotein a member of the National Academy of Sciences, and an molecules. Honorary Fellow of the Royal College of Pathologists. Two scientific societies bear her name. The woman they honorworked at herlaboratory bench, continuing to solve mysteries, until shortly before her death in 1981, at the age ofeighty-six.

FIRST ASSIGNMENT Rebecca Lancefield always insisted that she went to work at the Rockefeller because it was the only place that answered her job letters. Ifso, it was a piece ofvery good luck- for her and for the Rockefeller. She had been hired to assist OswaldAvery, a happenstance she described as the "most fortunate" of her scientific career. Avery is best known today for the identification ofDNA as the genetic material, a discovery he made with Colin MacLeod and Maclyn McCarty in the 1940s as an outgrowth of their studies of pneumonia bacteria. Long before the DNA finding, however, Avery was revered among microbiolo­ gists as possibly the mostbrilliant bacteriological investiga­ tor and mentor of his era. Although his interest was the pneumococcus bacte­ rium, Avery, along with other Rockefeller researchers, had turned his attention during World War I to the medical needs ofthe military. Following severe outbreaks ofstrep infections at military camps in Texas, he and his colleague Alphonse Dochez were attempting to determine whether one or several types of streptococci were involved in the epidemic. Within a year after Rebecca Lancefield's arrival, the team had found four distinct types. The inclusion of Page 3

her name on the paper reporting their results was, accord­ her husband completed his Ph.D. Following ing to Madyn McCarty, later to be Dr. Lancefield's his graduation, both accepted teaching posi­ laboratory associate, "a type of recognition seldom ac­ tions at the University ofOregon, Donald's corded to technical assistants in those days." home state. In 1922 Donald Lancefield re­ She had been lucky in other ways. Her background and ceived an appointment to the Columbia fac­ childhood might not have seemed to provide fertile soil for ultywhere he remained for many years before the cultivation ofa scientist, particularly a woman scientist. assuming the chairmanship of the Depart­ Herfamily, on both sides, had deep roots in the provincial, ment ofZoology at Queens College in New tradition-bound South. Witn their Army-officer father, York. Rebecca Lancefield was offered a sec­ Colonel William E. Craighill, Rebecca and her five sisters ond chance to do research at the Rockefeller, led a peripatetic life that resulted in erratic early schooling. working with streptococci bacteria to deter­ But Mrs. Craighill was a strong believer in education for mine their role in rheumatic fever. women, a conviction which laid the foundation for the careers ofRebecca and another daughter, Margaret, who MAKING ORDER became a successful physician. Some species ofmicroorganisms exist as one­ At Wellesley College, Rebecca Craighill happened to of-a-kind. Others come in many different va­ room with a zoology major. Originally intending to study rieties-streptococci notorious among French or English, she'd peer over her roommate's shoul­ them-as Rebecca Lancefield would learn. der and decided that doing science was more to her taste She had beeninvited toparticipate in rheu­ than conjugating verbs. Later, while working toward her matic fever studies being initiated at The master's degree in bacteriology and genetics at Columbia Rockefeller Institute's research hospital by University, she met a fellow student, Donald Lancefield, HomerSwift, a deliberate, painstaking physi­ with whom she would share a love ofscience and a loving cian-researcher fated to be nicknamed partnership to the end ofher life. "Speedy" by his laboratory juniors. Before The Lancefields' daughter, Jane Hersey, an editor, the war, Swift had tried without success to remembers a mother of"extraordinary energy" and ideal­ recover a specific bacterium from rheumatic istic commitment to science "for the thing itself," and a fever patients that could be definitively iden­ father who, in those pre-feminist days, could find his way tified as the causative agent of the disease. around the kitchen when "Mrs. L," as her Rockefeller When Dr. Lancefield joined his laboratory, colleagues affectionately called her, had to work late at the the bacterial bugs under suspicion were a Rebecca Lancefield and her lab. At a young age Mrs. Hersey recalls the pride she felt streptococcal group called "green" or viridans. husband Donald Lancefield in towards her mother because she was "different" from the Rebecca Lancefield endured two years of frustration. 1928 other mothers in their suburban Long Island community. The myriad green strains proved to be a lawless, perverse With the dose ofWorld War I and the termination of morass. With the patience and persistence that would Army funds for Avery's streptococcal research, Rebecca become her hallmark, she worked simultaneously for Swift Lancefield's first assignment at the Rockefeller came to an atthe Rockefeller and for herdoctoral degree at Columbia, end. She returned to Columbia as a research assistant while carrying racks of test tubes back and forth between labs. Page 4 Streptococcal chain

Positive reaction with antisera Precipitation reaction for M proteins determining streptococcal serotypes: Centrifugation to (A) Theant~en,orA1 separate bacteria from extract protein, is extractedfrom streptococcal chains by heating them for 10 minutes in an heated to 10(i' C acid solution. for 10 minutes (B) The bacterial portion is separated from the A1 protein I 1 2 3 5 6 9 12 I extract through centrifuga­ ... tion. The bacteria are Antibodies in discarded. Antisera 5 .. • (C) To determine the serotype ofthe streptococcus from which the A1 protein was (A) (B) (C) (D) (E) prepared, the extract is placed in capillary tubes and mixed with each ofa battery of antisera reactive with known She finally managed to ascertain that viridans was not the extract to precipitate, producing a whitish sediment in the serotypes. culprit in rheumatic fever. Fortunately for science, she test tube. This is called a precipitation reaction. If a (D) In this example, returned to work on hemolytic strep, the kind ofstrep she precipitation reaction occurs with the extract of an un­ antisera 5 shows a positive had studied with Avery. known serotype, it can be concluded that the serotype is reaction with the extract. The method she used, based onAvery's approach to the the same as the known one that was used to make the Thus, the serotype ofthe sorting out of pneumococcal types, is called serological antiserum. streptococcusfrom which the analysis. Simply stated, it works this way: Antigens are By the mid-1920s, Dr. Lancefield had isolated two anti­ extract was derived is Type 5. molecules on the surface ofinvader cells, like bacteria, that gens from hemolytic streptococci. One was type-specific, (E) A white cloudy a host organism recognizes as foreign. Strains ofbacteria that is, it was responsible for the differences in the various sedimentforms in the capil­ differing on the basis oftheir antigens are called serotypes. strains ofstrep that had been obtained from the patients of lary tube indicating a positive Serotypes are identified by means ofantibodies that com­ a Texas epidemic. The other antigen was species-specific; precipitation reaction. This bine only with the antigens ofthat serotype. The antibod­ it appeared to be present in all human strep strains. occurs when the antibodies ies are obtained by injecting an experimental animal with Oswald Avery (just down the hall from Lancefield on contained in the antisera bind antigens from a known serotype. Antibodies form in the the same floor ofthe hospital) had determined earlier that to the A1 proteinsfrom the animal's blood, or serum, which is then called antiserum. the type-specific antigens of pneumococci were made of streptococci being tested, Antiserum mixed with an extract of the bacteria of a polysaccharides, which are complex carbohydrates. To her forming an insoluble complex. specific serotype causes the type-specific protein in the surprise, and to the initial disbelief ofsome ofher fellow Page 5

researchers, Dr. Lancefield found her type-specific anti­ MAKING SENSE gens to be proteins. She labeled them M proteins (for the Despite its obvious importance and the years ofeffort she matt appearance of the colonies formed by bacteria with devoted to it, Rebecca Lancefield considered the classifica­ these antigens). Herspecies-specific antigen, however, did tion of streptococci as only the means of understanding prove to be a carbohydrate, and not long after, Avery and how basic streptococcal biology worked and how these his group found an analogous species-specific carbohy­ bacteria caused disease. The answer, she felt, lay in the drate antigen in pneumococci. antigens. From her studies ofthe M protein she discovered With these tools in hand, Rebecca Lancefield began to that its role was to protect the bacteria from attack by white make order. She identified the particular group ofhemo­ blood cells. Since the M protein is type-specific, even ifthe lytic streptococci chiefly responsible for human disease, host's antibodies did manage to overcome the onslaught which she called Group A, and went on to classifY more ofone particular strep type, the immunity acquired did not than sixty distinct strains. (The number today has climbed provide protection against subsequent infection by any of to eighty). She identified another hemolytic strep group, the other Group A serotypes. Group B, originally encountered in cattle disease, which This finding clarified the puzzle that had long baffled was found could also cause septicemia and infant meningi­ researchers as to why rheumatic fever is a frequently tis in human beings. In later years, she returned to Group recurring disease. "Her work on this antigen," Dr. Mc­ B and initiated studies that investigators are still pursuing. Carty has written, "provided the basis for a better under­ standing of the'epidemiology of the disease and a more rational approach to its control." During World War II, Rockefeller scientists were again called to service. Dr. Lancefield was appointed a civilian member ofthe Office ofScientific Research and Develop­ ment and a consultant to the Armed Forces Epidemiology Board on the Commission on Streptococcal and Staphylo­ coccal Diseases. When the commission was dissolved in 1972, its members continued to meet as an independent organization and in 1977 they adopted "The Lancefield Society" as its name. Throughout the war and after, Dr. Lancefield worked tirelessly to identifY strep strains and supply antisera to John]. Sampson presents military laboratories. To the end of her career, she Rebecca Lancefield with the responded to all such requests from researchers all over the American Heart Association world. A colleague remembers her jokingly complaining Research Achievement Award about the endless stream of queries addressed to her in October 1964. "Scotland Yard" at the Rockefeller, saying "nobody ever sends me easy ones." Page 6

Homer Swift retired in 1946. Maclyn McCarty moved Many honors came to her. She received the T. Duckett across the hall from Avery's laboratory to join forces with Jones Memorial Award ofthe Helen Hay Whitney Foun­ Dr. Lancefield. In his early training as a pediatrician he had dation, the American Heart Association Achievement Award cared for children with rheumatic fever and considered it "for accomplishment in the cardiovascular field," and the one of the most challenging problems in infectious dis­ Medal of the New York Academy of Medicine, among ease. In their laboratory, Dr. McCarty concentrated on others. In 1973, The Rockefeller University, her lifelong clinical aspects ofthe hospital's rheumatic fever service and scientific home, awarded her an honorary degree, as did RESEARCH PROFILES is published on research concerning the course of infection and the Wellesley College in 1976,onthe occasion of the college's four times a year by The Rockefeller University. This issue was written by chemical and biological properties ofthe streptococcal cell 100th anniversary, which happened to be the sixtieth Judith N. Schwartz. Special thanks are wall. Dr. Lancefield went on to identifY and study other anniversary ofLancefield's graduation. given to Dr. Vincent Fischetti, Dr. Maelyn McCarty, and Dr. Emil Gotsch­ streptococcal antigens. Streptococcal disease is not conquered. Treatment is lich of The Rockefeller University, as hard to come by for many poor people, and almost non­ well as to Mrs. Jane M.L. Hersey, Re­ becca Lancefield's daughter. Inquiries existent in many parts ofthe world. The search for a vaccine should be addressed to the University's MORE THAN A LEGEND against strep infections, as in the case of influenza and Public [nformation Office, 1230 York Avenue, New York 10021; or phone Although first and foremost a research scientist, Dr. other diseases caused by microorganisms that come in (212) 570-8967. Photograph: Upper Lancefield was unavoidably drawn into the larger world of many strains, has been a struggle both scientifically and in Left Hand Corner, Page I: Artifacts supplied by Dr. Vincent Fischetti, pho­ science. She was elected president ofthe Society ofAmeri­ terms offinancial support. tograph taken by Media Resources Serv­ can Bacteriologists in the 1940s and of the American Laboratories at Rockefeller and elsewhere continue the ice Center; Bottom: courtesy of Dr. Vincent Fischetti. Micrograph: Page 2: Association of Immunologists in the 1960s. She delivered research for which Rebecca Lancefield laid the foundation. courtesy ofDr. Vincent Fischetti. Pho­ major lectures in this country and abroad. Those were For five days this coming September, scientists from tograph: Page 3: courtesy of the Rockefeller Archive Center. Page 4: Il­ duties. Her pleasures, when not at the lab bench; were around the world will gather in Siena, Italy, for the lustration by Dennis Stillwell. Photo­ visits to and from fellow "strep hounds," as she called eleventh Lancefield International Symposium on Strepto­ graph: Page 5: courtesy ofRockefeller Archive Center. Design by the Stillwell them. To her juniors she was a caring, generous mentor cocci and Streptococcal Diseases, under the auspices of Group. NYC. © 1990 The Rockefeller and a model ofmeticulous science. Dr. Vincent Fischetti, the International Lancefield Society. University, Printed in the United States ofAmerica. who joined the laboratory of bacteriology and immunol­ In the newsletter of the American Society ofMicrobi­ Continuing its long-standing pol­ ogy in 1962, has put it succinctly: "IfMrs. L published it, ologists after her death, Lewis Wannamaker ofthe Univer­ icy to activell' support equality of op­ portunity tor all persons, The Rocketeller it was right." She never missed a lab celebration, and her sity of Minnesota Medical School wrote: "Inevitably, University rorbids discrimination on the family eggnog recipe remains a tradition at the lab's 'Mrs. L' became a legendary figure among microbiolo­ basis of ~ace) COIOf, religion, sex, na­ tional origin, or handicap. The Admini­ holiday festivities. Hating the New York heat, only in gists, but she was more than a legend. She was a patient, stration has an Affirmative Action Pro­ summer did she eagerly abandon her laboratory. At the hardworking scientist and a warm, soft-spoken person gram to increase the employment of women and members ofminority groups Marine Biological Laboratory in Cape Cod, she and her who made her contribution without fanfare and without in all areas ofelle university's activities. husband could do science, swim in the ocean, and enjoy feeling the need to compete with anyone except, possibly, the company of their family, which eventually included herself." 0 two grandsons.