The Wistar Institute

Series: Molecular Medicine Institutions

Giovanni Rovera, M.D., Director

Caspar Wistar, for whom the Wistar Institute is damaged over the years by fire and neglect. Rec- named, was a practicing Quaker and pacifist who ognizing the importance of the collection, Isaac would not fight during the Revolutionary War paid for its repair and established around it an but chose instead to care for those who were institution independent of, but with strong ties injured. Following the war, he went to Edin- to, the University. His wish was to provide a burgh and earned a medical degree, for which he setting for "searchers after new and original delivered a 44-page doctoral dissertation in per- knowledge." fect Latin. Over the years, Isaac contributed his fortune In 1787 at the age of 26, Caspar began the to the Institute's development, believing that he practice of medicine in Philadelphia, where he was "not constructing a mere plaything" for his became widely respected for his professional time, but rather "an enduring monument for a knowledge, deep compassion, and teaching skill. far-stretching future." Unfortunately, because of Twenty-one years later, he became Chair of the emphasis on the museum, which had acquired Anatomy Department at the University of Penn- more than 10,000 new specimens since its sylvania, succeeding his mentor and George founding, the scientific research conducted at Washington's physician, William Shippen. The Wistar Institute was largely ignored until Cultivated in the humanities as well as the after the turn of the century. sciences, Caspar had a breadth of knowledge and Under the guidance of Milton J. Greenman, public speaking skills that lured medical students named director of Wistar in 1905, the Institute from around the country. He reached still more finally began to fulfill Isaac's dream. Its first suc- with his book on anatomy, the first standard cess came from the development of the Wistar American text in the field. rat, later trademarked the WISTARAT, the first In 1816, two years before his death, Caspar standardized laboratory animal and an ideal ve- appointed William Edmonds Horner, a young hicle for the study of the human nervous system. physician, to be caretaker of his teaching aides, According to Institute records, these carefully which consisted of wooden models made by bred albino rats were treated with great affection; sculptor William Rush, and dried and wax- they received a diet that included rice pudding or injected human limbs and organs. Horner en- optional chocolate for dessert, and soothing vio- larged the collection with his own skeletal ma- lin music that caused them to click their teeth in terials and created the first anatomical museum approval. It is estimated that over half of today's in the United States, the Wistar and Horner Mu- laboratory rats are descendants of the original seum at the University of Pennsylvania. WISTARAT, which was bred and widely distrib- Nine years after Caspar's death, his great- uted from 1906 through the 1 940s. nephew, Isaac Jones Wistar, was born. Despite a At that same of restless and rebellious youth, Isaac time, University Pennsylva- grew up to nia graduate students and scientists from become a Civil War general, Philadelphia young lawyer, all over the world were access to and cultural leader. At the age of 63, he was given training approached by the University of Pennsylvania's in Wistar laboratories, and the publication and provost for help with the restoration of the circulation of scientific journals became a major Wistar and Horner Museum, which had been Wistar initiative. During World War I, when most of Europe was unable to print or purchase publications, the Wistar Institute Press sent out Address correspondence and reprint requests to: Diane Cut- thousands of dollars worth of free scientific jour- shall, Public Relations, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4268, U.S.A. Tel: 215-898- nals. By 1925, the Wistar Institute had become a 3716; Fax: 215-898-3715. center of American biology.

Not until the 1960s, however, was Wistar recently put into clinical use in Germany to pre- publicly recognized for its basic research when, vent metastasis in patients with surgically re- under the direction of Hilary Koprowski, Wistar sected advanced colon carcinoma. Wistar scien- scientists developed vaccines against rabies and tists also have identified several genes associated rubella. These vaccines were made possible by with leukemias, lymphomas, childhood tumors Leonard Hayflick's and Paul S. Moorhead's es- like Wilms' tumor, and soft tissue sarcomas. One tablishment of "Wl-38" (for the Wistar scientists' of Wistar's most prominent discoveries was the 38th try), a cell line of cloned human cells that bcl-2 gene, which alters in most lymphomas and were genetically identical and flourished in a test is a key player in programmed cell death. tube. Studies showed that almost any virus in- For the past several years, the Institute's im- troduced into the WI-38 cell line grew plentifully munology research has been driven by the desire and, through laboratory manipulations, could be to promote understanding of the ways in which transformed into a vaccine that was safer than the cytokine interleukin- 12 (IL- 12), discovered any using animal cells. by Wistar scientist Giorgio Trinchieri, steers the WI-38 also allowed Hayflick to make an- immune response to specific antigens, including other significant discovery. Troubled by the tumor antigens, and to develop new methodol- question of whether aging begins in the cells or ogies for vaccines, including cancer vaccines. the tissues they make up, Hayflick cloned cells One promising area of future research is on the from fetal tissue and placed them in a petri dish. adjuvant abilities of IL-12 to direct a cytotoxic Freed from the responsibility of supporting a response in conjunction with modern DNA or larger organism, the cells doubled again and viral vaccination. again until, quite suddenly, they stopped. From then on, they behaved as if they were aging, Under the leadership of Dr. Giovanni Ro- implying that somewhere in the nanoviscera of vera, The Wistar Institute currently has approx- each cell there may be a timer giving it only so imately 350 staff members, including around 130 much time to live. doctoral-level scientists, and more than 40 labo- Cancer research, begun in the 1940s when ratories grouped into four research programs: Warren H. Lewis, editor of Gray's Anatomy, and Molecular Genetics, Tumor Biology, Tumor Im- Margaret Reed Lewis joined the Wistar staff to munology, and Structural Biology. Although further their work in cytology, also became a each laboratory focuses on specific research high priority. In 1972, in recognition of its sig- goals, the programs are flexible and allow for the nificant achievements, Wistar was named one of cross-disciplinary interaction that innovative re- the country's first Basic Science Cancer Centers search demands. Also housed within the Insti- by the National Cancer Institute. This designa- tute are The Robert A. Fox Structural Biology tion, shared with only nine other U.S. institu- Center and The Albert R. Taxin Brain Tumor tions, has distinguished Wistar as a federally rec- Research Center. ognized center of excellence in the multifaceted Throughout its history, The Wistar Institute study of cancer. has pursued the dual mission of scientific re- Over the past 20 years, Wistar's investiga- search and education that Isaac Wistar began in tions into the causes and cures of cancer have honor of the great-uncle he had never known. focused on genetics and immunology, with Guided by its motto, Saving Lives Through Sci- Wistar scientists being among the first to develop encesm, it is armed for another century of com- monoclonal antibodies (MAbs), which detect bat against the major diseases of our time-can- and destroy cancer and other foreign cells. One cer, AIDS, Alzheimer's, atherosclerosis, and Wistar-developed MAb, known as 17-lA, was countless viral and parasitic infections.