SAGER, RUTH

(b. Chicago, Illinois, 7 February 1918; d. Brookline, Massachusetts, 29 March 1997), plant genetics, chloroplast genetics, cytoplasmic inheritance, cancer genetics.

Sager is known primarily for using classical genetic methods to demonstrate the presence of a hereditary system in the chloroplasts of plants and for establishing Chlamydomonas reinhardtii as a model organism for the study of chloroplasts. She is also credited with new techniques in mammalian somatic cell culture and the discovery of maspin, a tumor suppressor.

The Early Years and Education Ruth Sager was the only child born to Leon and Deborah Borovik Sager of Chicago, Illinois. Her mother died in the influenza epidemic in March 1919. Her father, an advertising executive, remarried (Hannah Shulman) and had two more children, Esther and Naomi. Ruth attended New Trier High School in Winnetka, Illinois, from 1930 to 1934. The Sager family emphasized the importance of the best education for their daughters, and after graduating from high school, Sager entered the University of Chicago in September 1934. Her interests originally lay in the humanities. She had planned to major in English, until she took a physiology course taught by Anton Carlson, where she discovered an interest in biology that would last her entire life. Sager received her BS in biology in December 1938 and was elected to Phi Beta Kappa. Her career, however, took a short detour after college.

As part of their philosophy that their daughters should be broadly educated, Sager’s parents took the three girls on a trip through Europe and the Middle East from February to May 1938. The trip delayed Sager’s graduation from college, but it exposed her to a way of life with which she would maintain contact for the rest of her life and helped direct her toward plant science.

While in Palestine, Sager visited a kibbutz, where she was impressed with the self-sufficiency of the kibbutzniks in creating a life in the desert. Although she wanted to return to Palestine, by 1938 emigration had been severely restricted. Instead, Ruth spent the next few years working on several training farms of Hashomer Hatzair, one of the Zionist organizations in the United States. While doing so, she became interested in the scientific aspects of desert farming and began studying plant physiology at Rutgers University in New Brunswick, New Jersey. She obtained a master’s degree in October 1944 on the mineral nutrition of tomato plants, and then spent the academic year working on the horticulture department farm at the University of Maryland. Although this was a phase of her life known only to a few other people, her interest in the practical applications of science stayed with her throughout her life.

A mutual correspondence during World War II with Seymour Melman, an army officer stationed in California, led to marriage in 1944. (They would divorce in 1960.) Both wanted to obtain graduate degrees and were accepted at Columbia University, where they matriculated in 1945. Sager began studying maize genetics under the direction of Marcus Rhoades, a well-known and widely respected plant geneticist. Another maize geneticist at Columbia was Barbara McClintock, a future Nobel laureate, who served as a reader on Sager’s dissertation and for

whom Sager occasionally did fieldwork. Sager received her PhD in December 1949 for her work on the waxy gene of maize, an attempt at identifying new mutations to help elucidate the role of that locus in starch synthesis. During the course of her graduate studies, she also became familiar with the phenomenon of cytoplasmic inheritance, a subject that had long been of interest to Rhoades, who had written his doctoral dissertation, as well as several additional papers, on the subject.

The presence of hereditary material outside of the nucleus had been suggested shortly after Gregor Mendel’s principles of inheritance became widely disseminated in 1900. In 1909, the Germans Edwin Baur and Carl Correns published the results of separate investigations on plants in which the inheritance of certain traits could not be explained by Mendel’s laws. Their suggestions that these traits were carried through the agency of the cytoplasm were met with skepticism by most of the genetics community at the time, although several researchers in Germany—including Otto Renner, Peter Michaelis, and Fritz von Wettstein—continued investigating the possibility. In the United States, however, where most geneticists emphasized the primacy of the nucleus’s role in heredity, few people conducted research on cytoplasmic inheritance, which was associated by some researchers with the discredited theory of Lamarckism, the inheritance of acquired characteristics. Beside Rhoades’s investigations of the phenomenon in maize, the most extensive genetic studies in the United States in the 1940s and 1950s were conducted by Tracy Sonneborn, a professor at Indiana University working with the microorganism Paramecium. Sager was very familiar with Sonneborn and his work, but in view of certain technical limitations with his experimental system, she took most of her research leads from the bacterial and viral geneticists.

Sager’s First Career In September 1949, with her dissertation nearly complete, Sager received a Merck Fellowship for a postdoctoral position in the laboratory of Dr. Samuel Granick at the Rockefeller Institute. Granick’s work focused on the biochemical pathways for the synthesis of porphyrin compounds, specifically hemoglobin and chlorophyll. Given the recent success of biochemical genetics in elucidating the synthesis pathways of amino acids in Neurospora by George Beadle and Edward Tatum, Granick considered that Sager’s background in plant physiology and genetics would be advantageous for a similar approach to ascertaining the synthesis pathway of chlorophyll.

Granick had been using the alga Chlorella in his biochemical studies, but it was not useful for studies modeled on Beadle and Tatum’s approach: Chlorella did not have a known sexual phase, a necessary prerequisite for conducting genetic crosses. Sager’s first objective was to find a suitable organism. To prepare for her work in Granick’s laboratory, Sager spent the summer of 1949 at the Hopkins Marine Station taking Cornelis Bernardus van Niel’s renowned summer microbiology course. While there, she learned about and acquired Chlamydomonas reinhardtii from Gilbert Morgan Smith, who had elucidated its life cycle, which included a sexual phase. Once back at Rockefeller, Sager and Granick determined the organism’s nutritional requirements, which resulted in a defined culture medium and, additionally, in methods for environmentally controlling the various phases of the alga’s life cycle.

From the beginning of her tenure in Granick’s laboratory, she sought to include cytoplasmic inheritance in the research program, and she began to exploit the Chlamydomonas system to that end. Because certain antibiotics were known to bleach chlorophyll, Sager began looking for their effects in Chlamydomonas. Following the leads of the recent successes in bacterial and microbial genetics and employing their techniques, she discovered several hereditary factors for streptomycin resistance: one was inherited in a Mendelian manner, but the other was always inherited in a non-Mendelian manner; that is, it always came from only one of the parents. On the basis of backcross data and their simplest explanation, Sager postulated that the factor was nonchromosomal. Citing the stability of the non-Mendelian resistant and sensitive phenotypes, Sager suggested that these factors represented alleles such as those associated with genes found on chromosomes. Although the material nature and location of these non-Mendelian elements remained unidentified, Sager postulated, on the basis of their behavior as unit factors, that they might be associated with an organelle, most probably the chloroplast.

While at Rockefeller, Sager had been appointed as an assistant of the institute in September 1951 and remained in that position for four years, continuing to work under Granick. Eventually, though, her desire to focus completely on cytoplasmic inheritance rather than on the biosynthesis of chlorophyll led her to leave his laboratory in 1955. She returned to Columbia University, where Francis Ryan, a microbial geneticist in the zoology department, provided her with bench space in his laboratory. Her position was listed as “research associate,” a nontenure-track position, and in 1960 she became senior research scientist. Sager independently funded her research and technicians through grants from the National Science Foundation, the National Institutes of Health, and the American Cancer Society.

Ryan was very interested in the nature of mutation, and soon after Sager arrived at Columbia, she began to investigate the origin of the mutations for resistance to streptomycin, an antibiotic that was known to irreversibly bleach the chloroplasts of Euglena, a photosynthetic flagellate. Prior to the 1940s, it was unclear whether mutations were induced by the agent to which the organism was resistant or whether the agent merely selected preexisting mutations for resistance. The question had been answered for most mutations by Max Delbrück and Salvator Luria with their fluctuation test (1943) and by Howard Newcombe with his respreading test (1949). They concluded that agents such as viruses and antibiotics selected for preexisting mutations; they did not induce them. Conducting the same tests on her streptomycin mutants, Sager’s results indicated that whereas the mutation on the chromosomal factor was shown to be preexisting, the nonchromosomal mutation for streptomycin resistance appeared to be induced by the antibiotic. Although the latter result would ultimately be explained by standard mechanisms of mutation induction, her interpretation helped to spark two decades of experiments on the nature of antibiotic mutations in organelles.

Up to this point, Sager and her longtime coworker, Zenta Ramanis, had been predominantly using classical genetic crossing and pedigree analysis to follow the behavior of the nonchromosomal factors. Sager remained tentative about their chemical composition and location in the cell. In 1962, Hans Ris and Walter Plaut had shown by specific staining that extranuclear DNA was present in the chloroplast of Chlamydomonas moewusii. In 1963, Alexander Rich and his coworkers had shown that whole-cell Chlamydomonas DNA contained a small amount of DNA that was lighter than the rest. Sager and her postdoctoral researcher, Masahiro Ishida, wanted to determine whether this satellite DNA might be associated with the nonchromosomal factors she had been investigating. Together they developed a method for isolating intact chloroplasts, from which they then extracted DNA and showed that although the major band of DNA was still present, the chloroplast extract was enriched for the satellite DNA and also RNA. This result suggested that molecules capable of serving as genes were located in the chloroplast.

In July 1963, shortly before this work appeared in the Proceedings of the National Academy, Francis Ryan suddenly died. By the end of August, Sager was notified that her appointment would end December 31, 1964. Although it was extended to December 1965, by February 1965 she had been offered and accepted a position as a full professor in the biology department at Hunter College (of the City University of New York). It was her first faculty appointment and began January 1966.

At Hunter, Sager continued her work on Chlamydomonas. She used ultraviolet light to increase the frequency of biparental (which she called “exceptional zygotes”). With them, she was able to make crosses and observe recombination and segregation. The results provided further evidence that the factors behaved similarly to nuclear genes, and so were probably located on a structure like a nuclear chromosome, but outside the nucleus. Also, because the factors were affected by ultraviolet light, like nucleic acids, she suggested that they might be composed of DNA.

With results from genetic crossing, Sager proposed a map for the hereditary factors. The first map was linear, and the genetic complement of the chloroplast appeared to be diploid. Further mapping work led her to a circular genome, which was confirmed by others, but who also demonstrated substantially more than two copies per chloroplast, a result Sager then confirmed herself through biochemical analysis.

Extending her molecular work, Sager noted that physical exclusion of the paternal chloroplast was not applicable in the case of Chlamydomonas and proposed that the mechanism of maternal inheritance was caused by selective elimination of the paternal DNA based upon a modification-restriction system much like that operating in bacteria. Discovery of differential methylation in maternal and paternal DNA and of a site-specific single-strand endonuclease in Chlamydomonas (the first identified in a eukaryote) provided supporting evidence. Sager did not resolve this question, which remained the subject of research in 2005.

Using classical genetic methods and the techniques of molecular biologists and microbial geneticists, Sager severed cytoplasmic inheritance from its negative Lamarckist and Lysenkoist associations and established the existence of second genetic system in plants. She is acknowledged as having laid the foundations for chloroplast genetics, especially establishing Chlamydomonas reinhardtii as a model organism, and her original and provocative explanations continued to stimulate research fifty years after her initial investigations.

For her work in this area, Sager was elected to the National Academy of Sciences in 1977 and received the Gilbert Morgan Smith medal, awarded for work on algae, from the academy in 1988. Sager’s pioneering work inspired a new generation, including Nicholas Gillham and Elizabeth Harris of the Chlamydomonas Center at Duke University and Ursula Goodenough at Washington University in St. Louis, among others. Sager’s work in chloroplast genetics has also provided additional support for the theory of the endosymbiotic origins of organelles promoted by Lynn Margulis of the University of Massachusetts–Amherst.

Sager’s Second Career Sager had always been concerned that her work should have practical applications, from her research in plant physiology to the genetics of maize. She never discussed the significance that her work on cytoplasmic inheritance held for new ideas about the origin and evolution of complex life-forms. Rather, even while Sager was still working with algae in the early 1960s, she thought about the implications that interactions between the cytoplasm and the nucleus held for cellular regulation and disease. Such interests led her to begin shifting the direction of her research career in the early 1970s toward the genetics of human cancer.

In August 1972, she received a Guggenheim Fellowship to spend a year in the laboratory of Dr. (later Sir) Michael Stoker, at the Imperial Cancer Research Fund in London, learning somatic cell culture. After her fellowship was finished, she returned to the United States, where she remarried in 1973. Her new spouse, Dr. Arthur Pardee, was a biochemist at Princeton University who had worked with François Jacob and Jacques Monod. When it was not possible for Sager to obtain a position at Princeton, she and Pardee moved to the Sidney Farber (later Dana-Farber) Cancer Institute, where they also obtained joint appointments with Harvard Medical School in Boston. In 1975, Sager was appointed professor of cellular genetics at the latter institution, one of the few women full professors, and chief of the Division of Cancer Genetics at Sidney Farber.

Sager began her work in cancer genetics by developing another experimental system. She established cell cultures of normal and tumorigenic Chinese hamster embryo fibroblasts (CHEF cells) that could be fused to show the effects of the different nuclei and cytoplasms on each other. Unlike the oncogene models for carcinogenesis, which postulated that the key step was the mutation of an oncogene that then promoted tumor growth, Sager’s work with CHEF cells suggested that the process also involved the loss or inactivation of tumor suppressor genes. Her results in the early 1980s reemphasized the idea of cancer as a two-step process involving tumor suppressor genes—not merely single oncogenes—and provided new hypotheses about the process.

Because of the high incidence of breast cancer in women, in the mid-1980s Sager transferred and extended her work on tumor suppressors to include human mammary epithelial cell cultures, again developing another culture system. She worked out a low-serum medium that supported long-term growth of primary cancer cells and identified markers that distinguished normal from tumor cells. Using CHEF and human cells, Sager identified several related genes called gro (growth response), which are members of a family of genes that encode cytokines, proteins that have regulatory, as well as anti-inflammatory, properties. The transcription of the gro genes appeared to be well regulated in normal cells but not in tumor cells, and this difference eventually led Sager to coin the term expression genetics. By that phrase she meant the investigation of regulatory changes, such as the loss of gene products (rather than loss or inactivation of the gene itself) in cancer cells. Such changes were thought to be additional foci for diagnosis and treatment.

In the early 1990s, Sager and her coworkers isolated more than one hundred possible tumor suppressor genes. One of the most significant of these was the gene for maspin, a serine protease inhibitor (serpin) that was expressed in normal cells but not in advanced breast cancer cells. Its action in inhibiting the spread of tumors became another focus of cancer research.

Even in her late seventies, Sager continued to maintain a laboratory, obtain research grants, and publish papers. In addition to the more than two hundred full scientific papers and fifty abstracts that she published over the course of her career, Sager also wrote two textbooks. The first was a collaboration with Francis Ryan resulting in what was described by some as the first molecular genetics book, Cell Heredity, which was published in 1961 to excellent reviews. Her second textbook, Cytoplasmic Genes and Organelles (1972), was also very well received, being the most comprehensive book on the subject at the time.

Sager spent many summers and much time writing at the Marine Biology Laboratory in Woods Hole, Massachusetts, where she maintained a second home so that she could visit as often as possible. In light of her love of Woods Hole, she was interred there after her death on 29 March 1997, of cancer.

Throughout her career, Sager traveled to meetings all over the world, gave talks at numerous universities, and made valuable contacts for her laboratory. In addition to the awards mentioned above, Sager’s scientific accomplishments were also recognized by election to Sigma Xi in 1947, a National Cancer Institute Outstanding Investigator Award in 1985, the Princess Takamatsu Award of Merit (Japan) in 1990, election to the Institute of Medicine in 1992, and the Alumni Medal from the University of Chicago in 1994.

BIBLIOGRAPHY

WORKS BY SAGER

“On the Mutability of the Waxy Locus in Maize.” Genetics 36 (1951): 510–540.

With Samuel Granick. “Nutritional Studies with Chlamydomonas reinhardi.” Annals of the New York Academy of Sciences 56 (1953): 831–838.

“Mendelian and Non-Mendelian Inheritance of Streptomycin Resistance in Chlamydomonas reinhardi.” Proceedings of the National Academy of Sciences of the United States of America 40 (1954): 356–363.

With Samuel Granick. “Nutritional Control of Sexuality in Chlamydomonas reinhardi.” Journal of General Physiology 37 (1954): 729–742.

“Inheritance in the Green Alga, Chlamydomonas reinhardi.” Genetics 40 (1955): 476–489.

“Genetic Systems in Chlamydomonas.” Science 132 (1960): 1459–1465.

With Francis J. Ryan. Cell Heredity. New York: John Wiley and Sons, 1961.

With Masahiro R. Ishida. “Chloroplast DNA in Chlamydomonas.” Proceedings of the National Academy of Sciences of the United States of America 50 (1963): 725–730.

“Genes outside the Chromosomes.” Scientific American 212 (1965): 71–79.

With Zenta Ramanis. “Recombination of Nonchromosomal Genes in Chlamydomonas.” Proceedings of the National Academy of Sciences of the United States of America 53 (1965): 1053–1061.

———. “Biparental Inheritance of Nonchromosomal Genes Induced by Ultraviolet Irradiation.” Proceedings of the National Academy of Sciences of the United States of America 58 (1967): 931–937.

Cytoplasmic Genes and Organelles. New York: Academic Press. 1972.

With Dorothy Lane. “Molecular Basis of Maternal Inheritance.” Proceedings of the National Academy of Sciences of the United States of America 69 (1972): 2410–2413.

With Robert Kitchin. “Selective Silencing of Eukaryotic DNA.” Science 189 (1975): 426–433.

With A. Neil Howell. “Tumorigenicity and Its Suppression in Cybrids of Mouse and Chinese Hamster Cell Lines.” Proceedings of the National Academy of Sciences of the United States of America 75 (1978): 2358–2362.

With William G. Burton and Constance T. Grabowy. “Role of Methylation in the Modification and Restriction of Chloroplast DNA in Chlamydomonas.” Proceedings of the National Academy of Sciences of the United States of America 76 (1979): 1390–1394.

With Ruth W. Craig. “Suppression of Tumorigenicity in Hybrids of Normal and Oncogene-Transformed CHEF Cells.” Proceedings of the National Academy of Sciences of the United States of America 82 (1985): 2062–2066.

“Genetic Suppression of Tumor Formation: A New Frontier in Cancer Research.” Cancer Research 46 (1986): 1573–1580.

With Anthony Anisowicz and Lee Bardwell. “Constitutive Overexpression of a Growth-Related Gene in Transformed Chinese Hamster and Human Cells.” Proceedings of the National Academy of Sciences of the United States of America 84 (1987): 7188–7192.

“Tumor Suppressor Genes: The Puzzle and the Promise.” Science 246 (1989): 1406–1412.

With Vimla Band. “Distinctive Traits of Normal and Tumor-Derived Human Mammary Epithelial Cells Expressed in a Medium That Supports Long-Term Growth of Both Cell Types.” Proceedings of the National Academy of Sciences of the United States of America 86 (1989): 1249–1253.

With Vimla Band, Deborah Zajchowski, and Victoria Kulesa. “Human Papilloma Virus DNAs Immortalize Normal Human Mammary Epithelial Cells and Reduce Their Growth Factor Requirements.” Proceedings of the National Academy of Sciences of the United States of America 87 (1990): 463–467.

With Stephen Haskill, et al. “Identification of Three Related Human GRO Genes Encoding Cytokine Functions.” Proceedings of the National Academy of Sciences of the United States of America 87 (1990): 7732–7736.

With Douglas K. Trask, et al. “Keratins as Markers That Distinguish Normal and Tumor-Derived Mammary Epithelial Cells.” Proceedings of the National Academy of Sciences of the United States of America 87 (1990): 2319–2323.

With Peng Liang, Lidia Averboukh, Khandan Keyomarsi, and Arthur B. Pardee.“Differential Display and Cloning of Messenger RNAs from Human Breast Cancer versus Mammary Epithelial Cells.” Cancer Research 52 (1992): 6966–6968.

With Zou Zhiqiang, et al. “Maspin, a Serpin with Tumor-Suppressing Activity in Human Mammary Epithelial Cells.” Science 263 (1994): 526–529.

With Shijie Sheng, Juliana Carey, Elisabeth A. Seftor, et al. “Maspin Acts at the Cell Membrane to Inhibit Invasion and Motility of Mammary and Prostatic Cancer Cells.” Proceedings of the National Academy of Sciences of the United States of America 93 (1996): 11669–11674.

“Expression Genetics in Cancer: Shifting the Focus from DNA to RNA.” Proceedings of the National Academy of Sciences of the United States of America 94 (1997): 952–955.

OTHER SOURCES

Biermann, Carol A. “Ruth Sager.” In Women in the Biological Sciences: A Biobibliographic Sourcebook, edited by Louise S. Grinstein, Carol A. Biermann, and Rose K. Rose. Westport, CT: Greenwood Press, 1997.

Brown, Patricia Stocking, and Gail K. Schmitt. “Ruth Sager.” In Notable American Women: A Biographical Dictionary, edited by Susan Ware. Cambridge, MA: Belknap Press of Harvard University Press, 2004.

Pardee, Arthur B. “Ruth Sager, 1918–1997.” Biographical Memoirs, vol. 80. Washington, DC: National Academy of Sciences, 2001.

———. “Ruth Sager, Geneticist.” In Maspin, edited by Mary

Hendrix. Georgetown, TX: Eurekah Publishing, 2001.

Sapp, Jan. Beyond the Gene. New York: Oxford University Press, 1987, pp. 201–206.

Gail K. Schmitt

Ruth Sager

Ruth Sager devoted her career to the study and teaching of genetics. She conducted groundbreaking research in chromosomal theory, disproving nineteenth-century Austrian botanist Gregor Johann Mendel's once-prevalent law of inheritance —a principle stating that chromosomal genes found in a cell's nucleus control the transmission of inherited characteristics.

Through her research beginning in the 1950s, Ruth Sager revealed that a second set of genes (nonchrosomomal in nature) also play a role in one's genetic composition. In addition to advancing the science of nonchromosomal genetics, she has worked to uncover various genetic mechanisms associated with cancer.

Born on February 7, 1918, in Chicago, Illinois, Ruth Sager was one of three girls in her family. Her father worked as an advertising executive, while her mother maintained an interest in academics and intellectual discourse. As a child, Sager did not display any particular interest in science. At the age of sixteen, she entered the University of Chicago, which required its students to take a diverse schedule of liberal arts classes. Sager happened into an undergraduate survey course on biology, sparking her interest in the field. In 1938, she graduated with a B.S. degree. After a brief vacation from education, Sager enrolled at Rutgers University and studied plant physiology, receiving an M.S. in 1944. Sager then continued her graduate work in genetics at Columbia University and in 1946 was awarded a fellowship to study with botanist Marcus Rhoades. In 1948 she received her Ph.D. from Columbia, and in 1949 she was named a Merck Fellow at the National Research Council.

Two years later, Sager joined the research staff at the Rockefeller Institute's biochemistry division as an assistant, working at first in conjunction with Yoshihiro Tsubo. There she began her work challenging the prevailing scientific idea that only the chromosomal genes played a significant role in genetics. Unlike many of her colleagues of the time, Sager speculated that genes which lay outside the chromosomes behave in a manner akin to that of chromosomal genes. In 1953 Sager uncovered hard data to support this theory. She had been studying heredity in Chlamydomonas, an alga found in muddy ponds, when she noted that a gene outside the chromosomes was necessary for the alga to survive in water containing streptomycin, an antimicrobial drug. Although the plant—which Sager nicknamed "Clammy"—normally reproduced asexually, Sager discovered that she could force it to reproduce sexually by withholding nitrogen from its environment. Using this tactic, Sager managed to cross male and females via sexual fertilization. If either of the parents had the streptomycin-resistant gene, Sager showed, the offspring exhibited it as well, providing definitive proof that this nonchromosomal trait was transmitted genetically.

During the time she studied "Clammy," Sager switched institutional affiliations, taking a post as a research associate in Columbia University's zoology department in 1955. The Public Health Service and National Science Foundations supported her work. In 1960 Sager publicized the results of her nonchromosomal genetics research in the first Gilbert Morgan Smith Memorial Lecture at Stanford University and a few months later in Philadelphia at the Society of American Bacteriologists. Toward the end of the year, her observations were published in Science magazine. As she continued her studies, she expanded her knowledge of the workings of nonchromosomal genes. Sager's further work showed that when the streptomycin-resistant alga mutated, these mutations occurred only in the non-chromosomal genes. She also theorized that nonchromosomal genes differed greatly from their chromosomal counterparts in the way they imparted hereditary information between generations. Her research has led her to speculate that nonchromosomal genes may evolve before the more common DNA chromosomes and that they may represent more closely early cellular life.

Sager continued announcing the results of her research at national and international gatherings of scientists. In the early 1960s Columbia University promoted her to the position of senior research associate, and she coauthored, along with Francis J. Ryan, a scientific textbook titled Cell Heredity. In 1963 she travelled to the Hague to talk about her work, and the following year she lectured in Edinburgh on nonchromosomal genes. In 1966 she accepted an offer to become a professor at Hunter College of the City University of New York. She remained in New York for nine years, spending the academic year of 1972 to 1973 abroad at the Imperial Cancer Research Fund Laboratory in London. The following year she married. Harvard University's Dana-Farber Cancer Institute lured her away from Hunter in 1975 with an offer to become professor of cellular genetics and head the Institute's Division of Cancer Genetics.

In the past twenty years, Sager's work centered on a variety of issues relating to cancer, such as tumor suppressor genes, breast cancer, and the genetic means by which cancer multiplies. Along with her colleagues at the Dana Farber Institute, Sager researched the means by which cancer multiplies and grows, in an attempt to understand and halt the mechanism of the deadly disease. She has likened the growth of cancer to Darwinian evolution in that cancer cells lose growth control and display chromosome instability. In 1983 she told reporter Anna Christensen that if researchers discover a way to prevent the chromosomal rearrangements, "we would have a potent weapon against cancer." She speculated that tumor suppressor genes may be the secret to halting cancer growth.

Sager continued to publish and serve on numerous scientific panels. In 1992 she offered scientific testimony at hearings of the Breast Cancer Coalition. A member of the Genetics Society of America, the American Society of Bacteriologists, and the New York Academy of Sciences, Sager was appointed to the National Academy of Sciences in 1977. An avid collector of modern art, she was also a member of the American Academy of Arts and Sciences.

On March 29, 1997, Sager died of cancer. At her death, she was chief of cancer genetics at the Dana-Farber Cancer Institute in Boston, which is affiliated with the Harvard Medical School.

Further Reading

Christensen, Anna, Potential Weapon in War on Cancer, United Press International, February 7, 1983.

The New York Times, April 4, 1997, p. A28. □