Editor’s Note: This history was written to outline the many scientific and medical achievements at Fox Chase Cancer Center. The authors are, respectively, Director of the Talbot Research Library & Media Services, Senior Director of Individual Giving, and Senior Vice President and Deputy Director at Fox Chase.
A Brief History of Fox Chase Cancer Center’s Scientific and Medical Achievements
By Beth Lewis, MLS; George Beschen; J. Robert Beck, MD
In July of 1904, a group of prominent Philadelphia physicians and laymen, concerned with rising cancer deaths in the city, met with the purpose of founding a hospital devoted to treating cancer. Funds were raised and the American Oncologic Hospital (AOH), one of the first cancer hospitals in the US, was opened in January of 1905. Its charter stated that its purpose was, “a hospital for the study of the cause, treatment, and prevention of cancer and other tumors, and the dissemination of knowledge on these subjects; for the treatment and care of persons affected with cancer … benefits shall be administered without regard to race, creed or color.” Early treatments at AOH included surgery and radiation.
A few years later, a young Philadelphia physician, Stanley P. Reimann, accepted a job as chief pathologist at Lankenau Hospital, with the promise of lab space that he could use to study cancer. He collaborated with Frederick S. Hammett. They believed that they had to study and understand normal growth before they could understand cancer, and later founded the journal Growth in 1937.
Early significant scientific work under Reimann’s leadership included Hammett’s finding of the effect of –SH on mammalian cell division, Gerritt Toennies’ work on the development of a lyophilized protein hydrolysate that would later be patented and used for intravenous feeding, and Madie Bennett’s groundbreaking work on homocysteine , which later lead to the discovery of Vitamin B12.
In the mid 1940’s Reimann’s research staff, called the Lankenau Hospital Research Institute (LHRI), had exceeded their space. During this time period, Reimann made significant appointments to the staff. Robert Briggs, an embryologist, and Jack Schultz, a geneticist, joined the staff in 1943. New space was found in Fox Chase on the Jeanes Hospital campus, and a research building was erected from a gift from the Pew family. A modern laboratory building was opened in 1949, and the institute then was called the Institute for Cancer Research (ICR).
Briggs had been a fellow at McGill University where he began to study tumorigenesis in developing frogs, focusing especially on the ability of a developing system to regress tumors. His work at the ICR involved studying the role of the nucleus in embryonic development. In 1952, working with Thomas King, he succeeded in transferring undifferentiated, embryonic nuclei to an embryonic cell, stimulating development. This was considered the first successful nuclear transplantation, and he is credited with the first successful cloning.
Schultz was one of the last students to study under Thomas Hunt Morgan, considered the world’s foremost geneticist, for his work in the role that the chromosome plays in heredity. At the ICR, Schultz started to work with chromosomes and was one of the first scientists interested in studying genetics in relation to cancer. In 1946 he was able to map two of the chromosomes associated with the nucleolus in preparations of human pachytene chromosomes and to show that, like the pachytene chromosomes of other species, they have distinctive chromomere patterns. His work formed some of the basic concepts underlying what became known as molecular biology.
In addition to his research, he encouraged scientific collaboration, which later led his student, David Hungerford, to collaborate with Peter Nowell at the University of Pennsylvania (Penn). Together, they discovered the Philadelphia Chromosome in 1959. This discovery provided the first conclusive evidence that cancer is a genetic disorder of somatic cells. Their research then lead to the development of a targeted drug therapy for cancer; imatinib (Gleevec) that targets the cancer-causing BCR-Abl protein produced by the Philadelphia Chromosome.
Other significant scientific work in the 1940s includes Hugh Creech’s work with Richard Peck and Robert Preston, who synthesized acridine nitrogen half mustard compounds that came to be known as “ICR chemicals.” Creech found that these chemicals were highly effective against ascites tumors in mice.
In 1949, A. Lindo Patterson, a physicist who developed the “Patterson function” to solve the phase problem in crystallography, joined the ICR. He collaborated with Jenny Glusker, a crystallographer, by applying X-ray crystallography to biological molecules, like DNA, to get a better understanding of protein structure. This is now a common practice in cancer research. Glusker, a professor emerita, received the 2014 William Procter Prize for Scientific Achievement, awarded by Sigma Xi.
In 1957, there was a change in senior leadership. Reimann retired and Timothy Talbot was recruited to be scientific director. Talbot had an impressive background. He had been at Sloan-Kettering where he worked with a group that first utilized steroid hormones to treat acute childhood leukemia, and prior to coming to ICR, Talbot did a fellowship at the National Cancer Institute, working with chemotherapeutic agents. Within his first year, he established a plan to establish a clinical research unit dedicated to clinical cancer investigation, appointed a scientific advisory committee, and set a goal to strengthen scientific endeavors. The development of a clinical research facility would not be fulfilled until 1964, but in 1961 a formal agreement was signed with Jeanes Hospital with the understanding that American Oncologic Hospital would join the Fox Chase campus at some time in the future. This agreement created the Fox Chase Center for Cancer and Medical Science.
Talbot recruited Thomas F. Anderson, a well-known phage geneticist, to ICR in 1958, with the promise in letting him work with an electron microscope. Anderson became internationally known for using an electron microscope to study viruses and bacteria. His colleague Robert Perry recalled that, “… his ability to master the instrument in its early stages of development, his invention of an ingenious method for specimen preservation, and his acute perspicacity in interpreting his observations resulted in pictures of historic importance. These included the first micrographs to clearly show infectious viruses attaching to and reproducing in their bacterial hosts and elegant detailed images of male (donor) bacteria transferring genetic information to female recipients. His research achievements helped elucidate several important mechanistic principles of virus-host interactions.” Anderson had come from the University of Pennsylvania and resulted in a formal agreement between the ICR and Penn. This provided ICR staff with an appointment at Penn and stimulated an interaction with Penn graduate students and collaboration with Penn faculty.
Talbot recruited Robert P. Perry from Penn and Beatrice Mintz from the University of Chicago, in 1960 and both became outstanding scientists. Mintz developed the mosaic mouse, making her a pioneer of genetic engineering techniques, and was among the first scientists to generate both transgenic and chimeric mammals. Mintz’s scientific work contributed to the understanding of genetic modification and cellular differentiation in cancer, particularly in melanoma. Among her many honors Mintz was elected to the Pontifical Society and received the 2011 Albert Szent-Gyorgyi Prize for Progress in Cancer Research.
Bob Perry was one of the few scientists in the world who did cutting-edge research on gene transcription in mammalian cells, specifically mammalian RNA synthesis, in the years before the technical revolutions in molecular biology. In 1962, Perry reported in a paper published in PNAS that ribosomal RNA was made in the nucleolus. In 1974, he made another groundbreaking discovery published in Cell, namely that mRNA molecules contain methylated base and sugar residues. After molecular cloning techniques became available, he cloned cDNAs for several ribosomal proteins and used them to study the structure and expression of the corresponding genes. In the early 1990s, Perry discovered a mammalian cDNA specifying a polypeptide, dubbed ‘‘CHD-1.” This was one of the first chromatin remodelers to be discovered in mammalian cells. Perry also later served in an administrative capacity when he served as Director of the ICR in the late 1960s.
In 1962, under Talbot’s leadership, the Institute for Cancer Research was one of the first four institutions to obtain what is now known as a Cancer Center Support Grant (CCSG). This grant, awarded from the National Cancer Institute, provides support for over a five-year period, with funds to support the science and infrastructure of the Institute. Fox Chase has had its CCSG continuously for the past half century.
In May 1963, the American Oncologic Hospital was formally included with the Fox Chase Center for Cancer and Medical Science. This affiliation included the Institute for Cancer Research, Jeanes Hospital, and the American Oncologic Hospital. By 1974, a new corporation was formed that was called the Fox Chase Cancer Center. This formal affiliation included the Institute for Cancer Research and the American Oncologic Hospital. Talbot became Fox Chase Cancer Center’s first president and Alfred G. Knudson was recruited to serve as Scientific Director in 1977.
Knudson came from MD Anderson where he developed his worldwide acclaimed “two-hit” theory of cancer causation published in 1971. Knudson was a pediatrician who had treated children with retinoblastoma and proposed his theory to explain the relationship between the hereditary and non-hereditary forms of the disease. The hypothesis predicted that retinoblastoma would develop only if both copies of a key gene are lost, or are inactivated and unable to function. Thus, it predicted the existence of tumor-suppressor genes, which can suppress cancer cell growth. Knudson received many awards for his work, including the Albert Lasker Award for Clinical Medical Research in 1998, the American Cancer Society Medal of Honor in 1989, the AACR Lifetime Achievement Award in 2005, and the Kyoto Prize in basic sciences. He was elected a member of the National Academy of Sciences in 1992.
Talbot successfully recruited Baruch Blumberg, who was then working at the National Institutes of Health, to become the Institute’s first Associate Director for Clinical Research, in 1964. Blumberg was interested in why people from different ethnic backgrounds responded to diseases differently, and traveled the world collecting thousands of blood samples from people in over 40 countries. While studying blood samples from Australian aborigines, he found an antigen that he called the Australia antigen. This proved to be part of the Hepatitis B virus and a key to the vaccine that he developed in his lab with Irv Millman. This became the world’s first cancer vaccine since Hepatitis B is a major cause of primary liver cancer. Jonathan Chernoff, currently Fox Chase Cancer Center’s Scientific Director, said that “…Barry prevented more cancer deaths than any person who’s ever lived.” Blumberg was awarded the Nobel Prize in Medicine or Physiology in 1976 for his work in discovering the virus and developing the Hepatitis B vaccine.
In 1963, Talbot was looking for a biochemist and recruited Irwin Rose from Yale University. Rose was attracted to ICR because it gave him the chance to learn from a wide range of researchers and was free from teaching commitments. Avram Hershko and Aaron Ciechanover came to the Rose lab in the ICR during many summer sabbaticals from Technion-Israel Institute of Technology in Haifa, Israel. Together, they won the Nobel Prize for Chemistry in 2004 for their work in the discovery of ubiquitin-mediated protein degradation; in other words, how proteins are broken down and recycled. This discovery established a new paradigm in biology and formed the basis for the development of Velcade, a drug approved to treat multiple myeloma.
Paul F. Engstrom was recruited to Fox Chase in 1970. Engstrom was one of the first trainees in medical oncology and became head of the department of medical oncology two years later. Talbot convinced Engstrom to change careers from that of treating patients to leading a research unit in population oncology (although Engstrom has remained an active clinician to date). In 1979 he established the first cancer prevention and control program at an NCI-designated cancer center. He has overseen Fox Chase programs in behavioral research, human genetics, epidemiologic research, and cancer prevention research, and served as the director of the Fox Chase Network, a group of Pennsylvania and New Jersey community hospitals. Some of Engstrom’s projects include the Early Detection Research Network that focuses on breast and ovarian cancer screening and diagnosis, and a founding member of the National Comprehensive Cancer Network Patient Guideline Committee. Engstrom has served as an advisor on cancer prevention and screening boards for the American Cancer Society, American Association of Cancer Institutes, American Society of Clinical Oncology, and the National Cancer Institute. He has received the Prevent Cancer Foundation’s Laurels Award for Lifetime Achievement in Cancer Prevention and the Annual Clinical Care Achievement Award from the Association of Community Cancer Centers. Engstrom has mentored many national leaders in cancer prevention and control, and has advised on the establishment of these programs in numerous NCI-designated cancer centers. He becomes an active emeritus professor in January 2019.
In the 1980s, Fox Chase researchers Melvin Bosma and Gayle Bosma discovered a mouse strain with severe combined immune deficiency (SCID). These mice lack T Cells and have no natural immunity so they are unable to reject tissue transplants. SCID mice have become valuable research tools by allowing researchers to study the immune system. SCID mice have been used worldwide to study cancer, HIV, malaria, and Dengue virus, and for years were the backbone of the Center’s technology transfer program.
In 1982, John R. Durant became president and CEO of Fox Chase Cancer Center, after founding the UAB Cancer Center and leading it to become NCI-designated. Under his leadership, Fox Chase’s staff doubled and its budget tripled, and Fox Chase established partnerships with community hospitals in Pennsylvania, New Jersey, and Delaware. This extended quality cancer care in the community and increased patient enrollment in clinical trials. Unfortunately, Durant’s wife Marlene became ill so they moved back to Alabama in 1988. Later, Durant became ASCO’s first Executive Vice President and Chief Executive Officer.
Robert C. Young became Fox Chase’s next President and CEO in 1988. Young came to Fox Chase from the National Cancer Institute where he served as Chief of the Medicine Branch. While at the NCI, Young became part of a group of five investigators, AKA “the gang of five”, who developed the first curative regimens for Hodgkin lymphoma and diffuse aggressive lymphomas. Under Young’s leadership, Fox Chase expanded its facilities, recruited top talent, and secured its standing as a national leader in basic and cancer research. During his tenure at Fox Chase, Young also served as President of the American Society for Clinical Oncology (ASCO).
In the early 1990s Fox Chase initiated its chemoprevention research program. The concept of treating healthy individuals to prevent cancer was a ground breaking idea at this time. Cancer chemoprevention uses medicines and nutrients to help prevent cancer and lower one’s risk of developing cancer, similar to using medicine to lower cholesterol and blood pressure to reduce heart disease.
In 1991 Mary Daly established one of the first risk assessment programs in the country to serve individuals with a family history of breast and /or ovarian cancer. The program offers genetic counseling and testing, screening, and the opportunity to participate in prevention studies. Since its founding, the program has expanded to provide services to people who are at risk for developing prostate, gastrointestinal, melanoma, kidney, endocrine and other cancers. Her research into the communication of genetic risk for breast cancer within families has identified several important socio-cultural correlates of successful communication. Daly has initiated studies of ovarian cancer screening modalities, quality of life after prophylactic surgery and serum biomarkers of breast and ovarian cancer risk. Daly is a leader in the design of educational programs in cancer genetics and cancer risk for both high risk individuals and for their healthcare providers. She is the past president of the American Society of Preventive Oncology and holds the Timothy Talbot Endowed Chair in Cancer Research. Prior to coming to Fox Chase, Daly helped develop the first bone marrow transplant program operated by the Department of Defense. She received the Air Force’s Meritorious Service Medal in 1990. Dr. Daly recently retired as Chair of Cancer Genetics, and is currently an active emerita at Fox Chase.
In 1992 the National Institutes of Health named Fox Chase as one of four institutions chosen to analyze genetic data for the Human Genome Project. Directed by Kenneth H. Buetow, the FCCC team also assembled part of the genetic map and contributed to a database for researchers worldwide.
Also during this time, Fox Chase scientists Joseph R. Testa, Philip Tsichlis, and Alfonso Bellacosa identified the protein AKT. A major driver of cancer development, AKT hinders the process that kills abnormal cancer cells. Initial studies link AKT overexpression to ovarian and pancreatic cancers but further work makes the connection to other cancers. The findings mark the first evidence of a recurrent genetic alteration in a cell signaling pathway that plays a central role in tumor development. Testa and Bellacosa are current professors at Fox Chase; Testa has been awarded the Stanley Reimann medal, the Center’s highest single honor.
Many of the nation’s academic cancer centers formed the National Comprehensive Cancer Network (NCCN) in 1995. Fox Chase was one of the founding members. This alliance was formed to ensure the highest quality, most cost-effective cancer care based on state-of the art treatment guidelines and outcomes research. NCCN’s headquarters were at Fox Chase, and now reside in nearby Fort Washington, PA.
Also in 1995, molecular biologist Jonathan Chernoff discovered and characterized MST1 and MST2 enzymes. These enzymes suppress cell proliferation and survival and act as important tumor suppressors in human and animal cancers. Chernoff’s discoveries suggest that manipulating the MST pathway activity may prove to be a potential therapy in liver, pancreatic, and other cancers. Chernoff is currently Deputy Director and Chief Scientific Officer at Fox Chase.
At the end of the 1990s Fox Chase scientist Dietmar Kappes discovered a mouse with a mutation in a master regulator that controls T cell fate. Years later, he identified the gene as Th-POK and shows that its dysregulation causes lymphoid transformation. This was significant because it linked cell development with how cancer cells develop. Dr. Kappes is a current professor at the Center.
Fox Chase became the first US cancer center and the first hospital in Pennsylvania to earn the American Nurses Association Magnet Award for Nursing Excellence in 2000. Magnet status certifies that Fox Chase meets the gold standard in nursing, including shared governance, research, and outstanding clinical care. Magnet has been renewed consistently, and Fox Chase is one of only eight organizations worldwide that have earned the designation five times in a row.
As the world moved into the 21st century, Fox Chase became the first cancer center in the world to use magnetic resonance imaging (MRI) to design more precise radiation plans for patients, setting a new standard. Over the course of the next decade, the department of radiation oncology pioneered the use of several state-of-the-art technologies including the bat ultrasound, CT on Rails, and Calypso beacons. These technologies enabled the radiation to be more precise and reduce side effects.
The results of a clinical trial led by Robert F. Ozols in 2003 demonstrated the efficacy of a new chemotherapy regimen combining paclitaxel and carboplatin to treat women with ovarian cancer. This study established a new standard of care used worldwide since the new regimen was less toxic, easier to administer, and cut infusion time from 24 hours to 4 hours. Ozols and Young have received numerous honors for their work in combination chemotherapies, sharing the Bristol Myers Award in 2002.
In 2006, Fox Chase and its faculty received several distinguished awards. Fox Chase Cancer Center received the highly competitive Susan G. Komen Breast Cancer Foundation 2007 Interdisciplinary Breast Fellowship Award; Kenneth S. Zaret received the MERIT (Method to Extend Research in Time) Award from the National Institutes of Health (NIH), and V. Craig Jordan received the 2006 American Cancer Society Award for Chemoprevention form the American Society of Clinical Oncology. Additionally, radiation oncology pioneer Gerald Hanks was named as one of its first class of fellows by the American Society for Therapeutic Radiology and Oncology (ASTRO).
In 2007, molecular biologist Erica Golemis discovered that a signaling circuit involving two proteins can dismantle cilia, antenna-like structures that detect signals controlling cell growth and contributing to malignant changes that lead to cancer. The implications of this discovery can also be applied to other developmental disorders, in addition to cancer. Golemis is a Deputy Scientific Director at Fox Chase
Fox Chase named Michael V. Seiden as President and CEO in 2007 upon the retirement of Robert Young. Prior to coming to Fox Chase, Seiden led the gynecologic cancer program at Dana-Farber / Harvard Cancer Center and was chief of the clinical research unit at Massachusetts General Hospital’s division of cancer medicine. Under his leadership Seiden advanced translational research efforts and positioned Fox Chase for an affiliation with the Temple University Health System in 2012.
Among Seiden’s accomplishments was the promotion of Robert G. Uzzo to Professor and Chair of Surgical Oncology. As both a surgeon and researcher, Uzzo is an internationally renowned leader in the field of urologic oncology. His interests include organ preserving surgeries, robotic and minimally invasive surgeries, complex urological reconstructions, adjuvant therapies for his risk urologic tumors and, non-surgical management of low risk tumors. He is a national principal investigator on multiple adjuvant kidney cancer clinical trials evaluating both targeted anti-angiogenic and immunotherapies. He is currently the president of the Society of Urologic Oncology (SUO) Clinical Trials Consortium and the author of more than 400 chapters, articles, books, and abstracts on urologic tumors. In 2018, Uzzo received the SUO Medal from the Society for his significant contributions to the field of urologic oncology. This prestigious award is presented to one member of SUO annually.
Fox Chase started its Nurse Navigation program in 2010 with two breast navigators in an effort to improve patients’ experience. The program’s success led to expansion to 16 navigators in ten disease areas within five years. This program helps patients throughout the entire treatment process, by reducing barriers, providing education, and connecting them to needed resources and services.
In this decade, current Fox Chase scientist Jeffrey R. Peterson cross-indexed the activity of 180 kinase inhibitors against more than 300 kinases, yielding valuable information on which inhibitors block which kinases, in a first of its kind effort. The team found that some compounds that had already been FDA approved for other diseases produce activity against some clinically important cancer targets. The kinase data was placed in a publicly available online database to enable scientists to develop more precise cancer drugs.
Fox Chase geneticist Alfonso Bellacosa discovered in 2011 that a protein called TDG affects the process of demethylation, which reactivates genes that, when silenced, lead to cancer. Demethylating drugs work to reactivate these silences genes but also work on other genes unrelated to cancer resulting in side effects. By pinpointing a protein that activates the demethylation process this discovery opens the possibility of developing a more targeted cancer therapy that would only change the expression of specific genes, producing a better outcome with fewer side effects.
Also in 2011, Joseph R. Testa found that inherited mutations of the BAP1 tumor suppressor gene predispose affected families to developing mesothelioma, melanoma, meningioma, as well as kidney, breast, and basal cell carcinoma. Further investigation led Testa to conclude that a BAP1 mutation alone is not enough to cause the disease, but exposure to asbestos is also required. His discoveries can potentially improve early detection efforts by helping to identify high-risk individuals.
In 2012 Fox Chase became a member of the Temple University Health System. This affiliation provided Fox Chase the opportunity to increase research collaborations, expand clinical programs, and offer more services to more patients. Fox Chase serves as the “hub” of cancer services for the health system.
That same year Fox Chase immunologist and Deputy Scientific Director David Wiest found that mutations in a ribosomal protein called L22 hasten the development of lymphoma. This is unique because this was first to show that mutations in this class of proteins can trigger cancer development. This discovery provides a target for the creation of new treatments for lymphoma.
In 2013 Richard I. Fisher was named President and CEO of Fox Chase. Fisher was able to dramatically improve the Center’s financial health within two years. Dr. Fisher came to Fox Chase as a nationally recognized leader in hematologic cancer treatment and research and invigorated key clinical programs while optimizing Fox Chase’s relationship with Temple University Health System. During his tenure over 50 Temple University faculty members have joined the Cancer Center as investigators, and the medical oncology team and bone marrow transplant physicians at Temple University Hospital have become Fox Chase faculty.
Fisher’s key recruitments since assuming the presidency of the center include:
- Henry C. H. Fung, who has substantially strengthened the Temple-Fox Chase Bone Marrow Transplant Program.
- Martin J. Edelman, Professor and Chair of Hematology-Oncology. Edelman is an internationally known expert in thoracic oncology, who also serves as Deputy Director for Clinical Research.
- Mariusz Wasik, Professor and Chair of Pathology. Wasik is an international expert in hematopathology, who will serve as associate cancer center director for shared resources.
Most recently Ann Skalka, Scientific Director emerita, has been named the 2018 recipient of the William Procter Prize for Scientific Achievement. Dr. Skalka is internationally recognized for her contributions to our understanding of the biochemical mechanisms by which retroviruses, including the AIDS virus, replicate and insert their genetic material into the host genome. She has published more than 240 scientific papers and scholarly reviews, edited several books, and organized and presented at national and international meetings. She is also author of the soon-to-be-released book, Discovering Retroviruses, and is coauthor of the widely acclaimed text, Principles of Virology.