Wistar Institute

Philadelphia, United States of America

Connections Hilary Koprowski

America's first non-profit independent research institution, the Wistar Institute played an important role in the development of monoclonal antibodies and is today renowned for its cancer research and vaccine development.

The roots of the Wistar Institute go back to work of the physician Caspar Wistar, who from the early late 18th century started building up a collection of anatomical human specimens at the University of Philadelphia for teaching purposes and anatomical research. After Wistar's death the physicians William Edmonds Horner and Joseph Leidy continued to add to this collection. During the late 1880s a campaign was mounted to transfer the collection to new premises with the aim of creating an institution to further research in the biological and medical sciences.

The Wistar Institute officially opened in 1892, supported by funds from Colonel Isaac Wistar, the great nephew of Caspar Wistar. It was the first independent medical research institute established in the United States.

In 1906 the Wistar developed and bred the Wistar rat, the first standardised laboratory animal. Over half of all laboratory rats in use today are thought to descend from this breed. By 1925 the Institute had built a sold reputation in biology and was recognised internationally as a training ground for young scientists.

From the 1950s, under the leadership of the Polish virologist Hilary Koprowski, the Wistar Institute started to gain international recognition for its vaccine development and cancer research. In 1979 the Wistar gained worldwide attention for the fact that its scientists had been granted the first patent on monoclonal antibodies, a technology that would be at the forefront of the biotechnology revolution.

Today the Wistar Institute has more than 29 laboratories grouped around three research areas: gene expression and regulation, immunology and molecular and cellular oncogenesis. Multi-disciplinary in its approach, the focus of the Institute is to investigate all types of cancers as well as viral and autoimmune diseases.

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Wistar Institute: timeline of key events

Capsar's parents were Richard Wistar and Sarah Wyatt. He was the grandson of Caspar Wistar, a German immigrant, Quaker and glassmaker.1761-09-13T00:00:00+0000Caspar had developed an interest in medicine after attending to the wounded in the aftermath of the battle of Germantown. 1783-01-01T00:00:00+0000While in Scotland, Caspar was elected president of the Royal Medical Society of Edinburgh for two years due to his 'investigation of natural history'. Caspar dedicated his doctoral thesis to Benjamin Franklin and to William Cullen, a famous Scottish physician. 1786-01-01T00:00:00+0000He also succeeded Benjamin Rush as professor of chemistry at the College of Philadelphia.1787-01-01T00:00:00+00001793-01-01T00:00:00+00001808-01-01T00:00:00+00001811-01-01T00:00:00+00001818-01-22T00:00:00+0000The Institute was founded to honour the memory of the physician Caspar Wistar and preserve his collection of anatomical models as teaching aids and to further medical knowledge. It was founded by Caspar's great nephew, Isaac Wistar, a prominent Philadelphia lawyer and former Civil War Brigadier General. 1892-01-01T00:00:00+00001894-01-01T00:00:00+0000This was announced at a Conference of Anatomists convened at the Wistar Institute1905-01-01T00:00:00+0000Nearly half of all rats now used in research are descendants from the WistarRat. 1906-01-01T00:00:00+0000A virologist, Koprowski invented the world's first effective live polio vaccine while at Lederle Laboratories. He developed the vaccine by attenuating the virus in brain cells of a cotton rat. In January 1948 he injected the vaccine into himself. The vaccine had the advantage that it directly entered the intestinal tract and provided long-lasting immunity. Within a decade the vaccine had been adopted on four continents. Koprowski went on to become the director of the Wistar Institute where in the 1960s he led efforts to improve the rabies vaccine. He subsequently became the first scientist, together with colleagues, to hold a patent for monoclonal antibodies. Born to Jewish parents, Koprowski was forced to flee Poland in 1939 after Germany invaded the country. 1916-12-05T00:00:00+0000Key developer of vaccine against rubella virus1932-01-01T00:00:00+0000Klinman was an immunologist who developed the splenic focus assay, a tool that allowed analysis of antibody production derived from single clones of B cells. He used the tool to analyse immune tolerance and immune responses to influenza. In additon he invented the splenic fragment system, a technique that helped generate some of earliest monoclonal antibodies against viral antigens and cancer. 1937-03-23T00:00:00+00001952-01-01T00:00:00+00001957-01-01T00:00:00+0000Working with Hilary Koprowski, Plotkin worked on infectious diseases, including a report on the outbreak of anthrax among millworkers1957-01-01T00:00:00+0000The phenomenon was observed in human fibroblasts (WI-38). It was named the 'Hayflick Limit' after Leonard Hayflick who discovered it. His work was published in L Hayflick, PS Moorhead, 'The serial cultivation of human diploid cell strains', Experimental Cell Research, 25/3 (1961), 585-621. The Hayflick Limit is now known to relate to genetic instability in aging cells and the development of cancer.1961-12-01T00:00:00+0000Created by Leonard Hayflick and Paul S Moorhead.1962-01-01T00:00:00+0000Norman Klinman, an American immunologist, devises a splenic fragments culture technique for growing antibodies.1969-01-01T00:00:00+0000The vaccine, RA27/3 had been developed by a team headed by Stanley Plotkin.1969-01-01T00:00:00+00001972-01-01T00:00:00+0000Swiss-born immunologist Walter Gerhard cultivates single antibodies with known specificity against influenza viruses using Klinman's splenic fragment technique.1975-01-01T00:00:00+0000Koprowski uses myeloma cells from Milstein's laboratory to generate monoclonal antibodies against tumour antigens. This work forms the basis of the first patent later awarded for monoclonal antibodies.1976-09-01T00:00:00+0000Hilary Koprowski, Polish born virologist and Carlo Croce, Italian born geneticist, both based at the Wistar Institute, file for the first US patent for monoclonal antibodies. The antibodies are made against viral antigens using cells supplied from Milstein's laboratory in September 1976. 1977-06-01T00:00:00+0000Hilary Koprowski, Polish-born virologist and director of the Wistar Institute, together with American entrepreneur Michael Wall establish Centocor with Dutch-born biochemist Hubert Schoemaker and American scientist Ted Allen. Located in Philadelphia, Centocor is the second American company established to commercialise monoclonal antibodies for medical diagnostics and therapeutics.1979-05-01T00:00:00+0000Hilary Koprowski, Polish-born virologist, and colleagues granted US patent for monoclonal antibodies against tumour antigens (US Patent 4,172,124). The patent helps in the building of Centocor, the second American biotechnology set up to commercialise monoclonal antibodies. It also causes a major political controversy in Britain as the patent makes broad claims, essentially patenting the technique first developed by Cesar Milstein and George Kohler in 1975.1979-10-01T00:00:00+0000The vaccine was developed by Stanley Plotkin, Hilary Koprowski and Tadeusz Wiktor at the Wistar Institute1980-01-01T00:00:00+0000Tests begin with 17-1A, also known as edrecolomab, a monoclonal antibody developed at the Wistar Institute. 1980-12-01T00:00:00+0000M Kobayashi, L Fitz, M Ryan, RM Hewick, SC Clark, S Chan, R Loudon, F Sherman, B Perussia, G Trinchieri, ' Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes', Journal Expermental Medicine', 170 (1989), 827-45.1989-09-01T00:00:00+0000Developed to treat Gram-negative sepsis, Centoxin originated from research conducted by Henry Kaplan and Nelson Teng based at Stanford University. It was licensed to Centocor, a small biotechnology company in Philadelphia. Following the FDA's request for more information, Centocor watched US$1.5 billion of its market capitalisation disappear. The news also had a devastating impact on other companies developing monoclonal antibody drugs. 1992-02-20T00:00:00+00001993-01-01T00:00:00+0000German regulatory authorities approve edrecolomab (Panorex) as an adjuvant treatment for post-operative colorectal cancer. The monoclonal antibody, originally known as 17-1A, was developed at the Wistar Institute and commercially developed for market by Centocor. 1995-01-01T00:00:00+0000Developed by William Wunner at the Wistar Institute1995-01-01T00:00:00+0000Research conducted by a team lead by Martha Jordan and published in Nature Immunology2001-03-28T00:00:00+0000Research led by Frank J Rauscher, published in Genes and Development.2002-04-14T00:00:00+0000Headed by Laszlo Otvos the research was published in the European Journal of Biochemistry.2002-08-07T00:00:00+0000Research carried out by Ramin Shiekhattar published in Journal of Biological Chemistry. 2002-08-20T00:00:00+0000Research led by Rajasekharan Somasundaram and Dorothee Herlyn published in Cancer Research.2002-09-14T00:00:00+0000The diagnostic, called NeutroSpectT, uses a monoclonal antibody, SSEA1, discovered at the Wistar Institute and developed by Palatin Technologies.2004-04-05T00:00:00+0000Research led by Laszlo Otvos published in Molecular Pharmceutics.2004-05-01T00:00:00+0000Study conducted by team led by Shelley Berger published in Molecular Cell.2005-02-17T00:00:00+0000The vaccine RotaTeq took 25 years to develop. It was developed by Stanley Plotkin, H Fred Clark and Paul Offit.2006-01-01T00:00:00+0000Research conducted by collaboration between Wistar Institute and Vienna Biocenter, published in 'Nature'.2006-11-15T00:00:00+0000Research led by Emmanuel Skordalakes published in the journal 'Structure'. 2007-11-13T00:00:00+0000Achieved by Emmanuel Skordalakes2008-01-01T00:00:00+0000Published in 'Nature Medicine', the system deloys glycoprotein D fused with genes from target antigens to increase the immune response. The work was led by Hildegund C.J. Ertl.2008-01-31T00:00:00+0000Klinman was an American immunologist who developed the splenic focus assay, a tool that allowed analysis of antibody production derived from single clones of B cells. He used the tool to analyse immune tolerance and immune responses to influenza. In additon he invented the splenic fragment system, a technique that helped generate some of earliest monoclonal antibodies against viral antigens and cancer.2010-05-04T00:00:00+0000A Polish-born virologist, Koprowski invented the world's first effective live polio vaccine while at Lederle Laboratories. He developed the vaccine by attenuating the virus in brain cells of a cotton rat. In January 1948 he injected the vaccine into himself. The vaccine had the advantage that it directly entered the intestinal tract and provided long-lasting immunity. Within a decade the vaccine had been adopted on four continents. Koprowski went on to become the director of the Wistar Institute where in the 1960s he led efforts to improve the rabies vaccine. He subsequently became the first scientist, together with colleagues, to hold a patent for monoclonal antibodies. Born to Jewish parents, Koprowski was forced to flee Poland in 1939 after Germany invaded the country. 2013-04-11T00:00:00+0000Vaccine developed by David Weiner together with collaborators at Inovio Pharmaceuticals, Inc., GeneOne Life Science, Inc., National Microbiology Laboratory at the Public Health Agency of Canada, and the University of Pennsylvania.2016-06-23T00:00:00+0000Research carried out by a team led by Dimitry I Gabriolvich. 2016-08-05T00:00:00+0000
Date Event People Places
13 Sep 1761Caspar Wistar was born in PhiladelphiaWistar Institute
1783Caspar Wistar received his Batchelor of Medicine from the University of PennsylvaniaWistar Institute
1786Caspar Wistar received his Doctor of Medicine degree from the University of EdinburghWistar Institute
1787Caspar Wistar appointed physician to the Philadelphia Dispensary, elected to the College of Physicians of Philadelphia and to the American Philosophical SocietyWistar Institute
1793Caspar Wistar became staff member of the Pennsylvania Hospital and elected curator of the American Philosophical SocietyWistar Institute
1808Caspar Wistar appointed sole professor of anatomy, midwifery and surgery at the University of PennsylvaniaWistar Institute
1811 - 1814Caspar Wistar published his two volumes of 'A System of Anatomy for the Use of Students of Medicine', the first American anatomy textbookWistar Institute
22 Jan 1818Caspar Wistar diedWistar Institute
1892Establishment of the Wistar InstituteWistar Institute
1894Opening of new building for the Wistar Institute designed to house its museum of anatonmical models and foster researchWistar Institute
1905Research made the principle objective of the Wistar InstituteWistar Institute
1906Creation of the first standardised animal model for research - the WistarRatWistar Institute
5 Dec 1916Hilary Koprowski was born in Warsaw, PolandKoprowskiLederle Laboratories, Wistar Institute
1932Stanley Plotkin born in New York City, USAPlotkinWistar Institute
23 Mar 1937Norman Klinman was born in Philadelphia, Pennsylvania, USAKlinmanWistar Institute, University of Pennsylvania
1952Stanley Plotkin graduated from New York UniversityPlotkinWistar Institute
1957Hilary Koprowski appointed fifth director of the Wistar InstituteKoprowskiWistar Institute
1957Stanley Plotkin assigned to work temporarily at Wistar Institute by CDC of US Public Health ServicePlotkinWistar Institute
December 1961Normal cell population discovered to only be able to divide a limited number of times before it stopsHayflickWistar Institute
1962WI-38 cell line developed - important to development of vaccinesHayflick, MoorheadWistar Institute
1969Splenic fragment technique devised for growing antibodiesKlinmanWistar Institute
1969 - 1970First license approved in US and Europe for vaccine against rubella (German measles)PlotkinWistar Institute
1972Wistar Instute named National Cancer Institute - first research institution to gain such a titleWistar Institute
1975Short-lasting antibodies against influenza virus devisedGerhardWistar Institute
September 1976Cesar Milstein supplies myeloma cells to Hilary Koprowski at the Wistar Institute for producing monoclonal antibodiesKoprowski, MilsteinLaboratory of Molecular Biology, Wistar Institute
June 1977First US patent application filed for monoclonal antibodiesCroce, Koprowski, MilsteinWistar Institute
May 1979Centocor foundedKoprowski, Schoemaker, WallWistar Institute
October 1979First US patent for monoclonal antibodies grantedKoprowski, MilsteinWistar Institute
1980US licensed first rabies vaccine for human useKoprowski, Plotkin, WiktorWistar Institute
December 1980Clinical tials begin with a monoclonal antibody for the treatment of gastrointestinal cancerKoprowskiWistar Institute
September 1989Giorgio Trinchieri and colleagues identified interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancerKobayashi, Fitz, Ryan, Hewick, Clark, Chan, Loudon, Sherman, Perussia, TrinchieriWistar Institute
February 1992Monoclonal antibodies market crashed following FDA's call for more information for Centocor's drug, CentoxinSchoemaker, Koprowski, MilsteinCentocor, Wistar
1993Wistar Institute patented Bcl-2, the first of a family of genes associated with different types of cancerWistar Institute
1995First monoclonal antibody therapeutic for cancer approved for marketKoprowskiWistar Institute, Centocor
1995US licensed first wildlife rabies vaccineWistar Institute
March 2001Mechanism uncovered for the way the immune system generates regulatory T-cellsJordanWistar Institute
April 2002Identification of new enzyme for silencing certain genes, opening new avenues for cancer treatmentsRauscherWistar Institute
7 Aug 2002Scientists identified segment of insect-derived antimicrobial peptide called pyrrhocoricin necessary for killing off bacteria opening up possible avenue for developing new antibioticsOtvosWistar Institute
20 Aug 2002Link identified between genes responsible for neurofibromatosis, a common neurological disorder, and a protein thought to play role in Alzheimer's diseaseShiekhattarWistar Institute
14 Sep 2002Regulatory T cells discovered to restrain cytolytic T cells attacking cancer via messanger chemical called TGF-betaHerlyn, SomasundaramWistar Institute
April 2004US FDA approved new imaging agent for detecting difficult to diagnose cases of appendicitisWistar Institute, Palatin Technologies
May 2004Study published demonstrating feasibility of using insect-derived antimicrobial peptice as drug-delivery vehicle OtvosWistar Institute
February 2005Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular eventsBerger, EmreWistar Institute
2006Vaccine approved for preventing rotavirus, a major kiler of children Plotkin, Clark, OffitWistar Institute
15 Nov 2006New enzyme identified as suppressor of p53 protein, a key molecule for controlling cancer in humansBergerWistar Institute, Vienna Biocenter
13 Nov 2007Inappropriate activation of telomerase, an enzyme, shown to be associated with uncontrollable proliferation of cells seen in human cancersSkordalakesWistar Institute
2008Structure of telomerase, an enzyme that conserves the ends of chomosomes, was decodedWistar Institute
31 Jan 2008New vaccine delivery system unveiled for preventing viral diseasesErtlWistar Institute
4 May 2010Norman Klinman died in San Diego, California, USAKlinmanWistar Institute, University of Pennsylvania
11 Apr 2013Hilary Koprowski diedKoprowskiLederle Laboratories, Wistar Institute
23 Jun 2016FDA approved first clinical trial for zika virus vaccineWeinerWistar Institute, University of Pennsylvania, Inovio Pharmaceuticals, GeneOne Life Science, Public Health Agency of Canada
August 2016Marker identified for myeloid-derived suppressor cells, a type of cell associated with tumour resistance to certain cancer treatmentsWistar Institute

13 Sep 1761

Caspar Wistar was born in Philadelphia

1783

Caspar Wistar received his Batchelor of Medicine from the University of Pennsylvania

1786

Caspar Wistar received his Doctor of Medicine degree from the University of Edinburgh

1787

Caspar Wistar appointed physician to the Philadelphia Dispensary, elected to the College of Physicians of Philadelphia and to the American Philosophical Society

1793

Caspar Wistar became staff member of the Pennsylvania Hospital and elected curator of the American Philosophical Society

1808

Caspar Wistar appointed sole professor of anatomy, midwifery and surgery at the University of Pennsylvania

1811 - 1814

Caspar Wistar published his two volumes of 'A System of Anatomy for the Use of Students of Medicine', the first American anatomy textbook

22 Jan 1818

Caspar Wistar died

1892

Establishment of the Wistar Institute

1894

Opening of new building for the Wistar Institute designed to house its museum of anatonmical models and foster research

1905

Research made the principle objective of the Wistar Institute

1906

Creation of the first standardised animal model for research - the WistarRat

5 Dec 1916

Hilary Koprowski was born in Warsaw, Poland

1932

Stanley Plotkin born in New York City, USA

23 Mar 1937

Norman Klinman was born in Philadelphia, Pennsylvania, USA

1952

Stanley Plotkin graduated from New York University

1957

Hilary Koprowski appointed fifth director of the Wistar Institute

1957

Stanley Plotkin assigned to work temporarily at Wistar Institute by CDC of US Public Health Service

Dec 1961

Normal cell population discovered to only be able to divide a limited number of times before it stops

1962

WI-38 cell line developed - important to development of vaccines

1969

Splenic fragment technique devised for growing antibodies

1969 - 1970

First license approved in US and Europe for vaccine against rubella (German measles)

1972

Wistar Instute named National Cancer Institute - first research institution to gain such a title

1975

Short-lasting antibodies against influenza virus devised

Sep 1976

Cesar Milstein supplies myeloma cells to Hilary Koprowski at the Wistar Institute for producing monoclonal antibodies

Jun 1977

First US patent application filed for monoclonal antibodies

May 1979

Centocor founded

Oct 1979

First US patent for monoclonal antibodies granted

1980

US licensed first rabies vaccine for human use

Dec 1980

Clinical tials begin with a monoclonal antibody for the treatment of gastrointestinal cancer

Sep 1989

Giorgio Trinchieri and colleagues identified interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancer

Feb 1992

Monoclonal antibodies market crashed following FDA's call for more information for Centocor's drug, Centoxin

1993

Wistar Institute patented Bcl-2, the first of a family of genes associated with different types of cancer

1995

First monoclonal antibody therapeutic for cancer approved for market

1995

US licensed first wildlife rabies vaccine

Mar 2001

Mechanism uncovered for the way the immune system generates regulatory T-cells

Apr 2002

Identification of new enzyme for silencing certain genes, opening new avenues for cancer treatments

7 Aug 2002

Scientists identified segment of insect-derived antimicrobial peptide called pyrrhocoricin necessary for killing off bacteria opening up possible avenue for developing new antibiotics

20 Aug 2002

Link identified between genes responsible for neurofibromatosis, a common neurological disorder, and a protein thought to play role in Alzheimer's disease

14 Sep 2002

Regulatory T cells discovered to restrain cytolytic T cells attacking cancer via messanger chemical called TGF-beta

Apr 2004

US FDA approved new imaging agent for detecting difficult to diagnose cases of appendicitis

May 2004

Study published demonstrating feasibility of using insect-derived antimicrobial peptice as drug-delivery vehicle

Feb 2005

Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular events

2006

Vaccine approved for preventing rotavirus, a major kiler of children

15 Nov 2006

New enzyme identified as suppressor of p53 protein, a key molecule for controlling cancer in humans

13 Nov 2007

Inappropriate activation of telomerase, an enzyme, shown to be associated with uncontrollable proliferation of cells seen in human cancers

2008

Structure of telomerase, an enzyme that conserves the ends of chomosomes, was decoded

31 Jan 2008

New vaccine delivery system unveiled for preventing viral diseases

4 May 2010

Norman Klinman died in San Diego, California, USA

11 Apr 2013

Hilary Koprowski died

23 Jun 2016

FDA approved first clinical trial for zika virus vaccine

Aug 2016

Marker identified for myeloid-derived suppressor cells, a type of cell associated with tumour resistance to certain cancer treatments

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