Journal of Virology
August 2013, volume 87, issue 15
http://jvi.asm.org/content/current
In Memoriam: Hilary Koprowski, 1916–2013
Stanley A. Plotkin
+ Author Affiliations
University of Pennsylvania, Philadelphia, Pennsylvania, USA
Koprowski, who died this year at the age of 96, was an extraordinary person. He excelled as an innovative scientist, a director of a research institute, a classical pianist, a composer of music, a connoisseur of art, and a polyglot world traveler. Born in Warsaw, Poland, where he obtained a medical degree, the Nazi invasion forced him and his wife, Irena, to flee to Italy, where he studied piano at the Accademia Nazionale di Santa Cecilia in Rome. During the Second World War, he managed to emigrate to Brazil, where he became a research assistant in the Rockefeller Foundation Laboratories. There, his work on yellow fever and several arboviruses so impressed the senior staff that a position was found for him at the Lederle Laboratories in Pearl River, New York. At Lederle, he began work leading to improved rabies vaccines and on attenuation of polio virus, the work for which he will be most remembered.
In the early 1950s, there was pessimism about the development of a polio vaccine subsequent to disastrous clinical trials of two experimental vaccines. Koprowski set out to attenuate the virus through adaptation to mouse brain. Starting with what later was identified as a type 2 strain, he achieved attenuation of neurovirulence in monkeys. After ingesting the orally administered vaccine himself, he arranged to vaccinate 20 mentally disabled children in collaboration with the physician in charge of the institution in which they resided, although it is said that his superiors at Lederle were unaware of this step. The ethical justification was the fear of poliovirus entering the institution, a common occurrence at the time. Although this first trial showed safety and immunogenicity of the strain, the presentation of the results at a later scientific meeting was greeted with shock because of the audacity of the work (1).
In the mid-1950s, cell culture became available, and Koprowski and Albert Sabin separately began to attenuate polioviruses by passage in monkey kidney cells. Both succeeded, and the Koprowski strains were tested extensively in the former Belgian Congo, his native Poland, and elsewhere (2). Nevertheless, because the Sabin strains were less neurovirulent in monkeys and were given successfully to millions of children in the former Soviet Union, they achieved licensure in the United States and adoption by the WHO for use throughout the world. During the battle between the oral polio vaccines, the atmosphere between Sabin and Koprowski became quite heated, with many colorful exchanges of insults, but afterwards they reestablished a friendship.
In 1957, Koprowski left Lederle to become Director of the Wistar Institute on the campus of the University of Pennsylvania in Philadelphia, a position he held for 35 years. The Wistar, established in 1892, was somewhat sleepy when he arrived, but he proceeded to convert it into a flourishing institution where there were no departments or walls between laboratories and where both fundamental and applied biology were at the leading edge. I also arrived in 1957, and like many others, I consider him to be my scientific father. Although the emphasis at Wistar was on virology and cancer, other areas, such as atherosclerosis, were investigated. The Wistar was a marvelous place to work in those years because of the international scientists Koprowski recruited and the stimulating atmosphere that he fostered. The lingua franca of Wistar was said to be broken English.
After losing the battle with Sabin over the polio vaccine, Koprowski switched to studies of fusion between somatic cells and eggs, subacute sclerosing encephalitis caused by measles, and “slow” viruses in the central nervous system (3, 4, 5). In that period, his laboratory also adapted rabies virus to human diploid cell culture, leading to a new and highly immunogenic rabies vaccine for humans (6). The gene for the rabies glycoprotein was also inserted into poxvirus vectors for immunization of wild animals, a technique that has successfully controlled wildlife rabies in parts of the world. It is no exaggeration to say that not since Pasteur had one person made more progress in preventing rabies than Koprowski. In addition, while Koprowski was director of Wistar, vaccines were also developed against rubella and rotaviruses.
A curious late sequel of polio vaccination in the Belgian Congo between 1957 and 1960 was the accusation in the late 1990s by certain journalists that Koprowski’s experimental vaccine had been made in chimpanzee cells contaminated by a simian immunodeficiency virus (SIV) that mutated to human immunodeficiency virus (HIV) and thus had introduced the virus into humans. Characteristically, Koprowski rejected the accusation with disdain, but in any case the accusation was refuted by a search of historical records, PCR of the supposed contaminated lot, and studies of SIV and HIV sequences and evolution which showed that HIV entered humans from wild chimpanzees early in the 20th century (7). Nevertheless, setting the matter to rest required international meetings and considerable work by his colleagues (8).
Koprowski’s scope in virology was breathtaking: his bibliography includes articles on at least 25 different viruses, including polio virus, rabies virus, simian virus 40 (SV40), parainfluenza virus type 1, herpes simplex virus, and many flaviviruses. His publication record includes over 900 articles.
When the technology to make monoclonal antibodies became available in the late 1970s, Koprowski founded the Centocor biotechnology company to make antibodies that could be used practically to treat viral infections and cancer. Late in his career, Koprowski set up the Biomedical Foundation to channel research toward making vaccine antigens in plants. Despite his age, he was actively promoting this field until the last year of his life.
Naturally, Koprowski received many awards in his lifetime, locally in the United States but also from Poland, France, Belgium, and Finland. He was a member of the National Academy of Sciences.
However, this recounting of his life does not fully convey the combination of charm, brilliance, and roguishness that struck anyone who came into contact with Hilary. He could converse in many languages about science, art, or music and had a sense of humor that included playing practical jokes. His piano concerts at Wistar and compositions, including short stories, plays, and an opera, were legendary. For his 70th birthday party, he came disguised as a disgruntled gentleman who was angry at the director of the Wistar Institute. Hilary could be an enfant terrible, but he was never boring, always full of ideas, and always stimulating. He left no one who met him unmoved, and none of us, friend or critic, will see his like again.
References available here: http://jvi.asm.org/content/87/15/8270.full
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