Dr. Charlotte Friend (born 1921)

Wikipedia 🌐 Charlotte Friend 

Born   March 11, 1921, in    New York City, New York      [HK005S][GDrive]   

Died  January 13, 1987 (aged 65), in   New York, New York      [HK005S][GDrive]   


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Charlotte Friend (March 11, 1921 – January 13, 1987) was an American virologist. She is best known for her discovery of the Friend leukemia virus.[1] She helped to establish the concept of the oncovirus, studied the role of the host immune response in disease development, and helped define modern retrovirology.

Family

Born and raised in New York, she was the youngest daughter of Russian Jewish emigrants, Morris Friend, a businessman, and Cecilia (Wolpin) Friend, a pharmacist. Friend had three siblings, consisting of two older sisters, Priscilla and Leafan, and a younger brother, Morris. When she was three years old, her father died, leaving her mother alone to raise four kids during the Great Depression. Her mother made sure all four of her kids would be able to finish their education, despite living on "Home Relief".[2]

Education and Research

She graduated from Hunter High School in 1940 and Hunter College in 1944.[3] The same year, she enlisted in the United States Navy.[4] As a lieutenant junior grade she worked in the hematology laboratory at U.S. Naval Hospital Shoemaker, California.[4] After the war ended she enrolled as a graduate student in the Department of Microbiology at Yale, where she received her PhD in 1950 with a thesis on the effects of sodium salicylate (aspirin) on antigen-antibody reactions[5] During her time at Yale she frequently traveled to New York to consult with Elvin Kabat and Michael Heidelberger, imminent immunologists at Columbia.[5] As a post-doc she worked in the Sloan-Kettering Institute under the direction of  [Cornelius Packard "Dusty" Rhoads (born 1898)]. While at Sloan-Kettering, she met Cecily Cannan Selby, who had recently gotten her Ph.D. from the Massachusetts Institute of Technology. Both of them were interested in cell structure. Once, when looking through an unused electron microscope at the university, the two decided to look at fine structures within the cells of the Ehrlich ascites carcinoma, a commonly used model for cancer research. What they found were structures in the cytoplasm of the cells which resembled those found in virus-infested cells. It was this incident that sparked Friend's interest in the possibility of cancer being caused by viruses, which became a main focus of her research. In 1966 she accepted a position as Professor and Director of the Center for Experimental Cell Biology at The Mount Sinai Hospital.

During her lifetime she was President of the Harvey Society, the American Association for Cancer Research and the New York Academy of Sciences and was the first woman to do so.[5] Charlotte Friend also served as a member of the Advisory Committee for the [Special Virus-Cancer Program] of the National Institutes of Health and a member of the Board of Scientific Counselors of the Division of Cancer Cause and Prevention of the [National Cancer Institute ]. Over the years, she served on a number of other advisory committees and on the editorial boards of several cancer and hematology journals. In all, she published 163 papers, 70 of which she wrote by herself or with one other author.

On her sixtieth birthday she was diagnosed with a lymphoma. She was insistent that her diagnosis remain secret, and continued to carry out her duties in her laboratory.[5] She died at the age of 65.

Legacy

Prizes

Selected works

References

External links

REFERENCES: Books and Research Papers

EVIDENCE TIMELINE

Late 1940s - Charlotte Friend (who becomes a Pioneer in Cancer Cell Biology) is a student, working in the lab of Dr. Alice E. Moore

Source : https://www.newyorkalmanack.com/2014/03/charlotte-friend-a-pioneer-in-cancer-cell-biology/ 

"Charlotte Friend: A Pioneer in Cancer Cell Biology"

March 10, 2014

The story of Charlotte Friend is a true New York story.  Friend was a noted microbiologist who made important contributions to the study of cancer.  She was an advocate for women’s rights and worked hard to improve the position of women in science.

Charlotte Friend was born March 11, 1921 in New York City, a city she loved.  She received a Bachelor’s degree from Hunter College in 1944 and then entered the Navy, where she was assigned to help direct a hematology laboratory in California.  She left the Navy in 1946 and began graduate work in microbiology at Yale University.  By the time she received her doctorate in 1950, Dr. Friend already had a position in the laboratory of [Dr. Alice E. Moore (born 1908)] at the Sloan-Kettering Institute in New York City. She stayed in New York for the rest of her life.

In 1956, Friend gave a paper at the annual meeting of the American Association for Cancer Research in which she stated that she had discovered a virus that caused a leukemia-like disorder in newborn mice.  She was roundly criticized for bringing up what was considered to be the old canard of viruses causing cancer.  Only [Dr. Francis Peyton Rous (born 1879)], who had made a similar announcement years before, spoke in her defense.

But the tide of change on this issue was turning in the face of mounting evidence.  Dr. Friend had not been the only researcher whose work suggested this.  By the next year, Friend had published her work in the prestigious Journal of Experimental Medicine, with the careful editing of Dr. Rous.  She was also supported by Jacob Furth, who announced that he had studied Dr. Friend’s pathologic material and that leukemia truly had been found to result from the new virus, which became known as the Friend leukemia virus.

Friend spent the following years investigating different aspects of the virus, as did many other researchers.  She worked with various collaborators, often cooperating in international research efforts.  Dr. Friend loved to travel and formed many long-term friendships with colleagues in Europe.  Her sabbatical years (1963 and 1975) were spent in laboratories in Australia, Israel, France and Italy.  She also attended many international meetings, often being one of only a handful of women scientists there. Still, while clearly social, she also maintained a very small laboratory staff and did not take on many graduate students to work with her.

Dr. Friend was very active in scientific associations and in outside professional activities such as grant reviewing and serving on editorial boards and advisory councils.  In the 1970s, when many associations ‘discovered’ their female members in reaction to the women’s movement, Dr. Friend was asked to assume leadership roles in several important organizations including:  chairman of the Gordon Conference (1973); member of the Board of Directors (1973-76) and president (1976) of the American Association for Cancer Research; president of the Harvey Society (1978/79); and president of the New York Academy of Sciences (1978).

In 1966, Charlotte Friend left Sloan-Kettering to become the first Director of the Center for Experimental Cell Biology and a Professor at the still developing Mount Sinai School of Medicine. She was the first and only female full Professor in the School when the faculty was officially formed in 1966.  She also served as a Professor in the Mount Sinai Graduate School of Biological Sciences.  At Mount Sinai, she established her own laboratory, which in 1967 was endowed as the Mollie B. Roth Laboratory.  Peyton Rous was the speaker at the event.  Still, it was an unending struggle to find the funding to keep the lab well-staffed and well equipped, a situation that got steadily harder as federal funding began to shrink in the 1970s.

The decline in federal funds for basic research led Dr. Friend to write several protest letters to congressmen and others in power.  This was a tact that she often took when a subject that mattered to her was threatened.  She wrote about many things, including her support for Israel, her opposition to anti-abortion measures, and in defense of women’s rights.

In 1971, Dr. Friend published another landmark paper, this one titled “Hemoglobin synthesis in murine virus-induced leukemic cells in vitro:  Stimulation of erythroid differentiation by dimethyl sulfoxide.”  The co-authors were William Scher, J. G. Holland and Toru Sato.  This paper described research on leukemia cells that had been made to differentiate, or take another step in the maturation process to become erythroid cells, thus stopping their cancer-like multiplication.  This work pointed to a whole new area of cancer treatment:  If instead of attacking cancer cells with toxic drugs, cancer cells could be targeted and made to mature, patients would be spared painful, sometimes deadly, and often ineffectual treatments.  Research continues today in this field.

In all, Dr. Friend published 163 papers, 70 of which she wrote by herself or with one other author, a rare feat in modern biomedical science.  Although diagnosed with lymphoma on her 60th birthday in 1981, she told few of her illness.  She continued to go about her work with all the energy she had, writing grants, serving on committees, and working in the lab.  Charlotte Friend died in January 1987.

In 1988, the Friend Papers were donated to the Mount Sinai Archives by Dr. Friend’s family. The finding aid for the collection is here: http://library.mssm.edu/services/archives/archives_collections/charlotte.shtml  For more information about Dr. Friend, contact the Mount Sinai Archives, a division of Academic Informatics &Technology of the Icahn School of Medicine at Mount Sinai.

1960 (June 04) - Buffalo Evening News : Alice e Moore, Charlotte Friend, AND Bernice Eddy !!

Mentioned :  Dr. Charlotte Friend (born 1921)  /  Bernice Elaine Eddy (born 1903)   /  Sarah Elizabeth Stewart (born 1905)   /  Dr. Alice E. Moore (born 1908)  

Full newspaper page : [HN02BT][GDrive]  /  Newspaper clip above : [HN02BU][GDrive] 

1961 (Sep 26)

Mentioned: Dr. Alice E. Moore (born 1908) ;  Dr. Charlotte Friend (born 1921) ; ...

Full newspaper page : [HN01JF][GDrive] 

1965 (April 19) - The Berkshire Eagle (Pittsfield, MA) - "Science women plan Bennington event"

Mentioned: Dr. Alice E. Moore (born 1908)  /  Dr. Charlotte Friend (born 1921)   /   Bernice Elaine Eddy (born 1903)   

Full newspaper page : [HN01JH][GDrive]

1977 - 

Does not mention Dr. Alice E. Moore once !!!

https://cancerres.aacrjournals.org/content/canres/37/5/1255.full.pdf 

1977-05-cancer-research-1255-by-charlotte-friend-full.pdf 

1992 (Dec 17) - Mentor Dr. Alice E. Moore died 

Source : [HL006T][GDrive]  /   See Dr. Alice E. Moore (born 1908)  

charlottre friend

https://www.nap.edu/download/4560

national academy of sciences - Biographical Memoirs

Volume 63

CHARLOTTE FRIEND

March 11, 1921–January 13, 1987

BY LEILA DIAMOND

IN 1956, at a meeting of the American Association for Cancer Research (A.A.C.R.) in Atlantic City, Charlotte Friend reported on the isolation of a virus that produced a fatal leukemia when inoculated into adult mice.1 This was a time when the concept of viruses causing cancer was still viewed with extreme skepticism and the presentation of such data by an attractive young woman not long out of graduate school was met with disbelief and derision.2 The audience's arguments against her findings were essentially the same as those Peyton Rous had heard in the early 1900's when he described a chicken tumor that was inducible by a transmissible agent. They argued, on the one hand, that the agent isolated was not a virus because it induced a malignant disease and, on the other, that the disease could not be a malignancy because it was virus-induced. However, the rapid confirmation of Friend's findings by the highly respected pathologist Jacob Furth led to a change in attitudes, and the scientific community soon realized that a virus which rapidly induces a malignant disease in adult mice provides an excellent model in which to study both viral oncology and the pathogenesis of neoplasia. Friend's virus became the primary system for research on viral

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leukemogenesis and today it is acknowledged that no one who works on tumor viruses fails to be touched by the contributions of Charlotte Friend.3

Charlotte Friend was born in 1921 in New York City on Houston Street in lower Manhattan to parents who had immigrated from Russia as young adults. Her mother had been trained as a pharmacist but gave up any professional ambitions to raise a family. Friend's father, a successful businessman, died when she was three years old and her mother moved the family of four children to the Bronx in order to be near, and have the support of, other relatives. The substantial inheritance left by Friend's father was dissipated in the financial disaster of 1929, and the fact that the family had to accept "home relief" from the city in order to survive had a lasting effect on Friend. She always admired her mother for having been able to keep the family together during this period and for never letting the children doubt that they would complete their education.

While growing up, Friend took advantage of all the opportunities and wonders that New York offered. She became a very knowledgeable and avid devotee of all its cultural activities and successfully competed for admission to Hunter College High School, a part of the city's excellent, tuition-free education system for gifted students. After finishing high school, she attended Hunter College at night while working in a physician's office during the day.

Upon graduating in 1943, Friend enlisted in the United States Navy and was assigned to Midshipmen's School at Smith College from which she graduated as an Ensign in April 1944. She was soon promoted to Lieutenant j.g. and appointed second-in-command of the hematology laboratory at the naval hospital in Shoemaker, California. From early childhood she had thought about becoming a scien-

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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tist, but this was her first real experience working in a laboratory and it convinced her that this was what she wanted to do with her life.

When the war ended, Friend had the financial support of the G.I. Bill of Rights to continue her schooling. She considered attending medical school but chose instead to enroll as a graduate student in the Department of Microbiology at Yale University. She already appreciated the importance of the advice and help of outstanding scientists for her research, and frequently came to New York City on weekends to consult with the eminent immunologists Elvin Kabat and Michael Heidelberger at Columbia. She received a Ph.D. from Yale in 1950 with a thesis on the effects of sodium salicylate (aspirin) on antigen-antibody reactions.

Friend was hired by Cornelius P. Rhoads, the director of what was then the new Sloan-Kettering Institute for Cancer Research, to work in the virus laboratory of Alice E. Moore. Rhoads was a very dynamic and enthusiastic individual who was extremely supportive of the members of his Institute, and he and Friend developed a strong mutual respect and admiration. At Sloan-Kettering, Friend met Cecily Cannan Selby, a recent Ph.D. from the Massachusetts Institute of Technology who was interested in cell structure. This was in the early days of electron microscopy and, when Selby found a microscope in the institute that was not being used, she and Friend decided to examine the fine structure of the cells of the Ehrlich ascites carcinoma, a transplantable tumor of mice that at the time was a commonly used model for cancer research. They unexpectedly observed cytoplasmic "particles of constant diameter in close array" that were similar to those seen in thin-sections of virus-infected cells,4 and Friend then sought to determine whether these particles were biologically active.

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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She inoculated cell-free extracts of the ascites cells into newborn mice, following a procedure for transmission of a murine leukemia virus that Ludwik Gross had introduced a few years earlier.5 The mice remained healthy over a fourteen-month period of observation but, when sacrificed and autopsied, six mice were found to have enlarged livers and spleens. Friend may have been surprised or dismayed to see what looked to be leukemia when she had inoculated an extract from carcinoma cells, but she was smart enough and curious enough to pursue the observation. Because newborn mice were unavailable, she injected cell suspensions from the enlarged spleens into adult mice and, within a few months, several had palpable spleens. By the third passage of either cell suspensions or filtrates of cell extracts, a high percentage of mice were developing leukemia with a latent period of only two to three weeks. The disease Friend was seeing was very different from the lymphoma induced by Gross's virus: it was characterized by erythroblastosis and profound anemia; it was transmissible in adult noninbred mice; and the latent period before the first symptoms appeared was very short, the latter fact being powerful evidence that the transmissible agent was directly involved in the induction of the leukemia.

It is interesting to note that the cytoplasmic particles originally seen by Selby and Friend4 were very different in size and structure from what was eventually proven to be the etiologic agent of Friend leukemia. In very elegant electron microscope studies done with Etienne deHarven, Friend found that her agent was a type-C virus6 or what later became classified, on the basis of genomic structure, as a retrovirus (reverse transcriptase-containing RNA virus). Friend and deHarven were among the first to describe the life cycle of these doughnut-shaped viruses that "budded," a

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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term suggested by their technician, from the cell surface of the leukemic cells.

Charlotte Friend never forgot the reception she and her new murine leukemia virus received at the 1956 A.A.C.R. meeting. Those who were present remember the dignity and courage with which she responded to the barrage of questions. She herself described the proceedings beautifully and in detail in her Presidential Address to the same society twenty years later.2 She said that, despite warnings that serious objections would be raised, "by no stretch of the imagination could the violent storm of controversy that erupted after (her) presentation have been anticipated." She wondered why her friend who chaired the session did not use Rous's plea to "keep open minds" as an opportunity to cool the heated atmosphere and finally bring the session to a close. It is a mark of her character that she did not reveal the identity of that chairman in her Presidential Address and that they always remained the dearest of friends.

She was proud to have "emerge(d) unbowed—if a little bloodied"2 from that experience and later was able to joke that those who persisted in their heretical beliefs about tumor viruses were being accused of having "either holes in their heads or holes in their filters." However, it may be that because of that rather traumatic experience, she never did develop into a strong, confident speaker. Throughout her career, whenever she had to give a talk, she was always very nervous and on edge in anticipation, and spent a great deal of time and effort writing out exactly what it was she wanted to say.

As co-editor of the Journal of Experimental Medicine and a strong supporter, Rous worked with Friend on the writing and editing of the first full-length publication describing the new virus.7 He made many suggestions regarding docu-

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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mentation, details and presentation, for he believed that she was "in a position to settle all doubts as concerns a virus causing leukemia in mice" if she presented what she had discovered "in a convincing way." The resulting publication provided the information the scientific community needed to accept the virus and to recognize its potential as an ideal model system with which to work.

The neoplastic nature of the disease induced was subsequently confirmed by the demonstration that transplantable solid tumors could be obtained with leukemic tissues from virus-infected mice. The leukemia was originally described as being not clearly granulocytic or monocytic, and it required extensive experimentation by Friend8 and others to demonstrate that the primary target for malignant transformation was, in fact, an erythroid precursor. Development of the disease is now thought to involve at least two events: an early stimulation of erythropoiesis followed by a clonal event that results in transplantable, immortal erythroleukemia cells.

Following the discovery of the Gross and Friend viruses, a number of other RNA viruses that induced leukemia in mice and other species were isolated. What had originally been disbelief now turned to accolades and Friend began to be honored for her work. In 1962 she received the Alfred P. Sloan Award for Cancer Research and elected to use the money to travel around the world, spending three-month periods in research institutes in France, Israel and Australia working with such scientists as Andre Lwoff, Leo Sachs and Donald Metcalf. She has written that the trip was one of the most important experiences of her life, a major reason being that she fulfilled her long-cherished dream of working at the Pasteur Institute.

Despite all the work that has been done on Friend Leu-

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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kemia Virus (FLV), we still understand very little about the molecular mechanisms by which it replicates and transforms. We do know that these mechanisms are extremely complex, so it is perhaps not surprising that over the years there have been disagreements and controversies regarding various aspects of the virus and the disease induced. The original virus isolate produced a leukemia associated with anemia but with its distribution to other laboratories and passage from host to host, virus strains that produced polycythemia rather than anemia appeared. These strains caused formation of macroscopic foci of primitive erythroid cells on the spleen surface which appeared prior to the hepatosplenomegaly and could be quantitated. These were foci shown to be due to the presence in preparations of polycythemia-inducing strains of a defective spleen focus-forming virus (SFFV) that was competent for cell transformation but not for virus replication. Some investigators reported that only the polycythemic strains of Friend Virus induced leukemia in adult mice and that the anemic strain was effective only in neonates. It was suggested that, contrary to what Friend had originally reported, more than one virus was required for the pathogenesis of the leukemia (see reviews by Friend and Pogo 9 and Ostertag et al.10).

Friend always resisted that idea. Perhaps the cool reception she and the virus received originally had sensitized her to what she may have considered criticism of that early work and her powers of observation. She maintained that in her hands, even after twenty years of continuous passage, the original anemic strain of FLV (FLV-A, what she referred to as the wild-type or prototype virus), its host range, latent period and age dependence, and the syndrome that that virus induced were no different from what she had first reported. She insisted that FLV-A did not con-

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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tain a defective, spleen focus-forming component11 and that it was different from the virus strains others may have worked with subsequently. Her friend Frank Lilly once "tried to convince her that she should be proud to have discovered not just one but in fact two viruses that were totally unique in the mouse leukemia virus world. But she would have nothing to do with that idea."12 And, indeed, others have shown that molecularly cloned FLV-A, with no SFFV component, induces an anemic form of an erythroproliferative disease in newborn mice which resembles the early stages of the disease induced by wild-type virus.13 However, no one has yet explained the mechanism by which the profound anemia induced by such virus in either newborns or adults progresses to leukemia.

Most virologists have taken the position that the Friend Virus is a complex composed of a defective SFFV that depends on replication-competent FLV for its own replication, and that both viruses are required for production of fatal leukemia in adult mice. Friend always acknowledged that during in vivo passage, virus variants might have arisen through recombination with cellular elements or endogenous viruses and was not surprised that an agent such as SFFV was found in some virus stocks. However, she wanted to understand what might have happened in other laboratories, to discuss the various possibilities with other investigators, and to analyze the passage histories of the various virus strains. Those such as Arthur Axelrad and Frank Lilly who had the patience for such discussions remained good, lifelong friends. Others who wanted to get on with it and not be overly concerned with what might have happened to the virus years ago lost touch with her and, unfortunately, perhaps lost respect for her and her accomplishments as well.

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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Rhoads, the director of Sloan-Kettering, had died in 1959 and the subsequent administration was much more structured than his had been. Friend did not have the warm relationship with the new director that she had had with Rhoads and did not think she was getting the recognition she deserved. Thus, she was receptive when approached about joining the faculty of the new medical school being organized at Mt. Sinai Hospital in New York. In 1966 she accepted a position there as professor and director of the Center for Experimental Cell Biology. She requested, and received, an appointment that carried no teaching responsibilities. She wanted to be free to do what she did best and most enjoyed—research. The new laboratory was rather modest in size and amenities, and a somewhat isolated basic science entity. In her new position, Friend was responsible for raising essentially all the money needed for staff, supplies, equipment and support services. She became tightly locked into the federal grant system for the major requirements of the center which she headed, and in her later years, this became a tremendous burden that interfered with her enjoyment of doing research.

It was at Mt. Sinai that Friend made another seminal scientific contribution when she showed that cancer cells can be induced to differentiate by an exogenous agent and, thereby, lose their ability to multiply. She had observed earlier that the cells of the solid tumors produced by transplantation of leukemic tissue from Friend Virus-inoculated mice showed no recognizable erythroid elements, but that the erythroid nature of the cells could be demonstrated under certain conditions. For example, Friend and Cecilia Patuleia were able to establish permanent cell lines in culture from the tumor cells and to show that, even when cloned, these cultures consisted of undifferentiated

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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cells and a small percentage of cells at various stages of erythroid maturation.14,15 Their observation that these malignant cells were, in fact, capable of undergoing maturation was met with disbelief by some colleagues, even though the evidence should have been incontrovertible from their slides and photographs. "How can tumor cells that have been in culture for 6 months give rise to erythroblasts?" they asked. "There must be a contaminant." But again in the face of skepticism, Friend persisted, knowing that her cell system provided a superb "model for the study of leukemia as a disease resulting from a maturation defect."16 She began to explore the possibility that the differentiation block in the leukemic cells could be removed.

This led her to the discovery that Friend erythroleukemia cells (FELC) in culture could be further stimulated to differentiate along the erythroid pathway by the addition of the solvent dimethyl sulfoxide (DMSO) to the medium.17 I had been using DMSO as a solvent for hydrophobic compounds in cell cultures. I remember her phoning one day to ask about the concentration to use for an experiment she wanted to try. A few days later she called back, bursting with excitement about her cells being "pinkies, all pink, all pink." Her associate, Bill Scher, also remembers her running up and down the hall holding up the tube with the pellet of pink cells for all to see. She went on to show that, with some highly inducible erythroleukemia cell lines, the percentage of benzidine-positive (hemoglobin-producing) cells could be increased to over 85 percent, from a baseline of 1 percent, after four-five days in medium containing DMSO. Friend had clearly and dramatically demonstrated that expression of the malignant phenotype could be reversed experimentally.

Her observation was quickly reproduced and confirmed

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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in other laboratories and it soon became apparent that the morphological and biochemical alterations that followed induction of differentiation were similar to those occurring in normal erythropoiesis. Friend cells became a widely used model for studying control of hemoglobin synthesis as well as for analyzing the overall regulation of gene expression in cell proliferation and differentiation.

This new discovery resulted in another exciting period of recognition for Friend. She was elected to the Hunter College Hall of Fame and received the Yale Science and Engineering Association Award. She was honored with the Dameshek Medal, the Prix Griffuel, and the Papanicolaou Award. In 1976 she was accorded the ultimate recognition by her peers, election to the National Academy of Sciences.

In the late 1960s a young Italian pathologist, Giovanni Rossi, spent several years working in Friend's laboratory. They became close scientific colleagues and devoted friends, and in 1977 when she had the opportunity to spend a sabbatical year abroad, she went to Rome where Rossi had settled. She had a wonderful time working at the Italian National Research Council Laboratory where Rita Levi-Montalcini was director. The two women had great respect for each other and when Friend left Rome, Professor Levi-Montalcini gave her an engraving entitled "The Spiral of Archimedes," done by her twin sister, Paola.

Charlotte Friend first learned that she had lymphoma on her sixtieth birthday in 1981. She told very few people and was adamant that others not know. She did not want those who might be reviewing her grants or manuscripts to be influenced one way or the other. Despite undergoing extensive, debilitating therapy, she continued to spend time in the laboratory, to write, to attend meetings and discuss work with other people, to send out manuscripts and grant

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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proposals and, when necessary, to argue with editors, reviewers and administrators. She did everything she could to keep her laboratory afloat, always with the hope that it would be perpetuated if she were no longer around. However, it had always been important to her that she stay on top of everything going on in her laboratory. She had preferred to do things herself and not to turn projects over to others. And so, she had never built up an active group of young investigators studying problems of interest to her. In the end, there was no one to maintain the center and continue her work.

One of Charlotte Friend's last public appearances was at Brandeis University, where she received an honorary Doctor of Science degree in May 1986. She was very proud to have been selected for this honor and left her hospital bed to make the trip to Waltham, Massachusetts. She participated in the commencement procession in a wheelchair and, despite a broiling sun, stayed for the entire lengthy ceremony. She died eight months later on January 13, 1987.

During the height of her career, Charlotte Friend was perhaps one of the most well-known and well-liked cell biologists and cancer scientists. She was a very warm and social person, albeit somewhat shy. She had a good sense of humor and a rather charming way of interacting with people. She was extremely generous when it came to distributing her virus (FLV) and her cells (FELC) to those who wanted to work with them, and she would give those investigators all the guidance and assistance they needed for their work. Many remember with pleasure visiting her laboratory, going to lunch, and talking about what they were doing or would do with the wonderful tools she had provided. And if they were from out of town, she always made sure they were properly looked after. Her apartment

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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in the Stuyvesant Town complex on East 14th Street came to be known as "The Friend Hotel," for friends and colleagues from near and far were welcome to stay there when visiting New York—and they frequently did, some for weeks at a time.

Charlotte Friend had a genuine concern for people and took an interest in their personal lives, their families, and their problems. She was always available to listen and frequently spent evenings in the laboratory or at home doing just that. She had a dedicated staff that would have followed her to the ends of the earth. Several, such as the pathologist Jamil Haddad and the technician J. Gilbert Holland, worked with her for over thirty years.

She served as the matriarch and leader of what was a very close-knit family. She was deeply devoted to her mother, who lived with her until her death in 1961, and to her siblings and nieces and nephews. It was she to whom the immediate and extended family turned for advice and help. She particularly enjoyed advising and assisting others with their medical problems and frequently boasted of "practicing medicine without a license," perhaps reflecting regrets about not having gone to medical school.

She was a renaissance woman who loved and knew intimately the theater, dance, music, opera, and literature. No matter how tired she was or how difficult the day had been, she would jump at the chance to see a new show if someone came up with a pair of tickets at the last minute. She enjoyed traveling, seeing new sights, and meeting different people. Wherever she went, there were two things she had to do: buy stamps for her brother Morris who was a collector, and get a memento of the trip for herself, usually a unique piece of jewelry or interesting work of art. But no matter where she had been and how much she had en-

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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joyed the trip, it was "The City" that thrilled her most and to which she returned with joy. She loved the view of the Manhattan skyline from her apartment and could never bring herself to move to a place that might be more convenient or more luxurious.

Charlotte Friend was a woman of strong convictions and a fighter, with no compunctions about defending her ideas and the causes in which she believed. For example, she wrote letters to newspaper editors and spoke up without fear in support of blacklisted academics and dissidents, even during the McCarthy and Nixon eras when doing so could jeopardize one's grants and career. She believed whole-heartedly in the State of Israel and was an outspoken defender of its policies. She was a fervent supporter of the women's movement and frequently, without fanfare, went out of her way to ensure that women were well-represented on symposium programs and advisory and review committees. She served as a role model for many women starting their careers at a time when there were not many such models.

In the 1970s, when the demands on the relatively few senior women scientists were enormous, she worked extremely hard as president of the American Association for Cancer Research, the New York Academy of Sciences, and the Harvey Society, the first woman so honored in the long history of that society. During this same period, she also served as a member of the Advisory Committee for the Virus Cancer Program of the National Institutes of Health and a member of the Board of Scientific Counselors of the Division of Cancer Cause and Prevention of the National Cancer Institute. Over the years, she served on a number of other advisory committees and on the editorial boards of several cancer and hematology journals. She took all

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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these responsibilities very seriously and was noted for her incisive reviews and for her thoughtful and astute comments in committee meetings.

Charlotte Friend used to say that she started an industry, and it was true. In the two decades following the initial isolation of FLV, perhaps a third of those doing cancer research spent some time working on one or the other of the model systems she had provided. Even today, many aspects of the Friend virus complex (FLV/SFFV) remain unique among tumor viruses so that it continues to be an important, widely utilized model system (reviewed in ref. 10). For example, it acts as an acute transforming virus but does not contain an oncogene. It is immuno-suppressive and, therefore, a model for human immuno-deficiency virus (HIV). It stimulates abnormal erythroid hyperplasia by binding of virus (SFFV) glycoprotein to a growth factor (erythropoietin) receptor, a novel mechanism that may explain how other viruses can interfere with normal growth regulation.

Friend paved the way for a great many other avenues of research. She was the first to show, using her virus, that animals could be immunized with retrovirus preparations and protected against development of the disease.18 Her experiments indicating that such protection is possible are frequently cited by those now trying to develop a vaccine against HIV. Leukemic cells induced by Friend Virus have been used in the first demonstration that a virus-induced malignancy requires for its expression the alteration or deletion of an "anticancer" or suppressor gene. Friend was one of the first to show that cells maintained in culture can actually undergo the successive steps leading to differentiation to a specific cell type. Her system was the forerunner for the establishment of other cell culture models to study

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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cytodifferentiation and the development of diverse lineages. Her demonstration of inducible differentiation of leukemic cells by DMSO has served as the inspiration, as well as the prototype, for evaluating the potential therapeutic effects of differentiation-inducing agents in human cancer.

Charlotte Friend was in the tradition of many women scientists who have made contributions to botany, astronomy and microbiology. She, too, was a naturalist, an observer and, in many ways, a loner. She enjoyed the aesthetics of biology, the overview rather than the molecular. She was an inventive, instinctive scientist who had fun doing science. She did not want a large laboratory, only her devoted staff and enough funding to be able "to play," as she called it. She did, however, seek recognition and fame, and this she achieved. Her ideas and discoveries have had, and will continue to have, a major impact on our thinking about the causes, prevention and cure of cancer.

CHARLOTTE FRIEND'S complete bibliography can be found in "Viral Oncogenesis and Cell Differentiation: The Contributions of Charlotte Friend," L. Diamond and S. R. Wolman, editors, Annals of the New York Academy of Sciences, vol. 567, pp. 5–13, 1989. This memoir was submitted October 9, 1990.

REFERENCES

1. C. Friend, "The Isolation of a Virus Causing a Malignant Disease of the Hematopoietic System in Adult Swiss Mice," Proc. Am. Assoc. Cancer Res. 2(1956):106.

2. C. Friend, "Presidential Address: The Coming of Age of Tumor Virology," Cancer Res. 37(1977):1255–63.

3. L. Diamond and S. R. Wolman, eds., "Viral Oncogenesis and Cell Differentiation: The Contributions of Charlotte Friend." (Ann. N.Y. Acad. Sci. 567, 1989).

4. C. C. Selby, C. E. Grey, S. Lichtenberg, C. Friend, A. Moore,

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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and J. J. Biesele, "Submicroscopic Particles Occasionally Found in the Ehrlich Mouse Ascites Tumor," Cancer Res. 14(1954):790–94.

5. L. Gross, "Pathogenic Properties, and 'Vertical' Transmission of the Mouse Leukemia Agent," Proc. Soc. Exp. Biol. Med. 78(1951):342–48.

6. E. deHarven and C. Friend, "Electron Microscope Study of a Cell-Free Induced Leukemia of the Mouse: A Preliminary Report." J. Biophys. Biochem. Cytol. 4(1958):151–56.

7. C. Friend, "Cell-Free Transmission in Adult Swiss Mice of a Disease Having the Character of a Leukemia," J. Exp. Med. 105(1957):307–18.

8. G. B. Rossi and C. Friend, "Erythrocytic Maturation of (Friend) Virus-induced Leukemic Cells in Spleen Clones," Proc. Natl. Acad. Sci. USA 58(1967):1373–80.

9. C. Friend and B. G.-T. Pogo, "The Molecular Pathology of Friend Erythroleukemia Virus Strains: An Overview," Biochim. Biophys. Acta. 780(1985):181–95.

10. W. Ostertag, C. Stocking, G. R. Johnson, N. Kluge, R. Kollek, T. Franz, and N. Hess, "Transforming Genes and Target Cells of Murine Spleen Focus-Forming Viruses." Adv. Cancer Res. 48(1987):193–355.

11. E. H. Brown, M. Zajac-Kaye, B. G.-T. Pogo, and C. Friend, "Rat Cells Infected with Anemia-Inducing Friend Leukemia Virus Contain Integrated Replication-Competent But Not Defective Proviral Genomes," Proc. Natl. Acad. Sci. USA 82(1985):5925–29.

12. F. Lilly, "Leukemia, Viruses, Development and the Real World," in: Viral Oncogenesis and Cell Differentiation: The Contributions of Charlotte Friend, eds. L. Diamond and S. R. Wolman (Ann. N.Y. Acad. Sci. 567:274–77, 1989).

13. A. I. Oliff, G. L. Hager, E. H. Change, E. M. Scolnick, H. W. Chan, and D. R. Lowry, "Transfection of Molecularly Cloned Friend Murine Leukemia Virus DNA Yields Highly Leukemogenic Helper-Independent Type C Virus," J. Virol. 33(1980):475–86.

14. C. Friend, M. C. Patuleia, and E. deHarven, "Erythrocyte Maturation in Vitro of Murine (Friend) Virus-Induced Leukemic Cells," Natl. Cancer Inst. Monogr. 22(1966):505–22.

15. M. C. Patuleia and C. Friend, "Tissue Culture Studies on Murine Virus-Induced Leukemia Cells: Isolation of Single Cells in Agar-Liquid Medium," Cancer Res. 27(1967):726–30.

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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16. C. Friend, "The Phenomenon of Differentiation in Murine Erythroleukemic Cells," The Harvey Lectures (New York: Academic Press, 1979):253–87.

17. C. Friend, W. Scher, J. G. Holland, and T. Sato, "Hemoglobin Synthesis in Murine Virus-Induced Leukemic Cells In Vitro: Stimulation of Erythroid Differentiation by Dimethyl Sulfoxide," Proc. Natl. Acad. Sci. USA 68(1971): 378–82.

18. C. Friend, "Immunological Relationships of a Filterable Agent Causing a Leukemia in Adult Mice. I. The Neutralization of Infectivity by Specific Antiserum," J. Exp. Med. 109(1959):217–28.

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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SELECTED BIBLIOGRAPHY

1953 A study of the effect of sodium salicylate and some structurally related compounds on antigen-antibody reaction in vitro. J. Immunol. 70:141–46.

1954 With C. C. Selby, C. E. Grey, S. Lichtenberg, A. Moore, and J. J. Biesele. Submicroscopic cytoplasmic particles occasionally found in the Ehrlich mouse ascites tumor. Cancer Res. 14:790–94.

1955 With F. Wroblewski and J. S. LaDue. Glutamic-oxaloacetic transaminase activity in serum in mice with viral hepatitis. J. Exp. Med. 102:699–704.

1956 With F. Wroblewski. Lactic dehydrogenase activity of serum in mice with transplantable leukemia. Science 124:173-74.

The isolation of a virus causing a malignant disease of the hematopoietic system in adult Swiss mice. Proc. Am. Assoc. Cancer Res. 2:106 (Abstract).

1957 Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia. J. Exp. Med. 105:307–18.

1958 With E. deHárven. Electron microscope study of a cell-free induced leukemia of the mouse: A preliminary report. J. Biophys. Biochem. Cytol. 4:151–56.

1959 With G. diMayorca, B. D. Eddy, S. E. Stewart, W. S. Hunter, and A. Bendich. Isolation of infectious deoxyribonucleic acid from SE polyoma-infected tissue culturest. Proc. Natl. Acad. Sci. USA 45:1805–8.

Immunological relationships of a filterable agent causing a leuke-

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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mia in adult mice. I. The neutralization of infectivity by specific antiserum. J. Exp. Med. 109:217–21.

1960 With J. R. Haddad. Tumor formation with transplants of spleen or liver from mice with virus-induced leukemia. J. Natl. Cancer Inst. 25:1279–89.

With E. deHarven. Further electron microscope studies of a mouse leukemia induced by cell-free filtrates. J. Biophys. Biochem. Cytol. 7:747–52.

1962 With F. Rapp. Detection of cytoplasmic deoxyribonucleic acid and nucleoproteins with antinuclear serum. Virology 17:497–99.

1964 With E. deHarven. Structure of virus particles partially purified from the blood of leukemic mice. Virology 23:119–24.

1966 With M. C. Patuleia and E. deHarven. Erythrocytic maturation in vitro of murine (Friend) virus-induced leukemic cells. Natl. Cancer Inst. Monogr. 22:505–22.

1967 With G. B. Rossi. Erythrocytic maturation of (Friend) virus-induced leukemic cells in spleen clones. Proc. Natl. Acad. Sci. USA 58:1373–80.

With M. C. Patuleia. Tissue culture studies on murine virus-induced leukemia cells: Isolation of single cells in agar-liquid medium. Cancer Res. 27:726–30.

1968 With G. B. Rossi. Transplantation immunity and the suppression of spleen colony formation by immunization with murine leukemia virus preparations (Friend). Int. J. Cancer 3:523–29.

1970 With G. B. Rossi. Further studies on the biological properties of

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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Friend virus-induced leukemic cells differentiating along the erythrocytic pathway. J. Cell. Physiol. 76:159–66.

1971 With W. Scher, J. G. Holland, and T. Sato. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro. Stimulation of erythroid differentiation by dimethyl sulfoxide. Proc. Natl. Acad. Sci. USA 68:378–82.

With W. Scher, J. G. Holland and T. Sato. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro. Partial purification and identification of hemoglobins. Blood 37:428–37.

1973 With H. D. Priesler, D. Housman, and W. Scher. The effects of 5-bromo-2'-deoxyuridine on the production of globin mRNA in dimethyl sulfoxide-stimulated Friend leukemia cells. Proc. Natl. Acad. Sci. USA 70:2956–59.

1977 Presidential address: The coming of age of tumor virology. Cancer Res. 37:1255–63.

1979 The phenomenon of differentiation in murine erythroleukemic cells. In The Harvey Lectures, pp. 253–87. New York: Academic Press.

With D. W. Golde, N. Bersch, D. Tsuei, and W. Marovitz. Transformation of DBA/2 fetal liver cells infected in vitro by the anemic strain of FLV. Proc. Natl. Acad. Sci. USA 76:962–66.

1980 With D. Tsuei and B. G.-T. Pogo. Variations in properties of virus released from morphologically different cell lines transformed in vitro by Friend leukemia virus. Proc. Natl. Acad. Sci. USA 77:5769–73.

1981 Murine virus–induced erythroleukemic cell lines. In Functionally Differentiated Cell Lines , ed. G. Sato, pp. 235–49. New York: Alan R. Liss, Inc.

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Suggested Citation:"6. Charlotte Friend." National Academy of Sciences. 1994. Biographical Memoirs: Volume 63. Washington, DC: The National Academies Press. doi: 10.17226/4560.

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1982 With B. G.-T. Pogo. Persistent infection of Friend erythroleukemia cells with vaccinia virus. Proc. Natl. Acad. Sci. USA 79:4805–9.

1985 With B. G.-T. Pogo. The molecular pathology of Friend erythroleukemia virus strains: An overview. Biochem. Biophys. Acta. 780:181–95.

With E. Brown, M. Zajac-Kaye, and B. G.-T. Pogo. Rat cells infected with anemia-inducing Friend leukemia virus contain integrated replication competent but not defective proviral genomes. Proc. Natl. Acad. Sci. USA 82:5925–29.