Career Lasting Influences

In this brief tribute to Hilary Koprowski, I wish to convey a small example of the often unintended but significant positive impact that Hilary had on the careers of many young scientists who spent time at The Wistar Institute. Although they may not have directly worked with Hilary, many had the privilege of benefiting enormously from his wisdom of what was scientifically important and his insight in recognizing scientific talent.

I literally showed up at the office of Lionel Manson at Wistar in the summer of 1975. The reason—I had applied as a graduate student to the Immunology Graduate Group program at the University of Pennsylvania and Dr. Manson was the Chair of the Group at that time. Unfortunately, they had lost half my graduate school application, although I was unaware of this until I arrived. Undaunted, I was initially permitted to enroll in the program part-time and Dr. Manson suggested I apply for a technical job at Wistar. I went straight to the personnel office and quickly obtained a position with Yasuhiro Hosaka. Again, unknown at the time, this was the first major influence Hilary had on my career. The major reason that Hilary had brought Hosaka to The Wistar Institute was because Hilary wanted to immortalize B cells. From his vaccine work, Hilary knew the importance of serological responses for clearing virus infections. Even at this early stage, he could envision the potential impact and importance of being able to produce virtually unlimited amounts of specific antibodies to viruses, cancers, and other targets.

Dr. Hosaka worked on Sendai virus, which is a paramyxovirus that fuses with cell membranes at neutral pH. The hope was that the virus could be used to fuse cells to generate immortalized B cells producing specific antibodies. In Hosaka's lab, I gained my initial knowledge and skills in working with and growing viruses that I would later use throughout my career. I also established a relationship with Dr. Hosaka for future collaborations and a lifelong friendship until his death.

After my first semester, I became a full-time graduate student at Penn. It was before this that Hilary had heard about the discovery of the major histocompatibility restriction (MHC) of T cell responses to viruses. He was interested in all facets of vaccination and anti-viral immunity so he asked Peter Doherty to join Wistar. It was a clear demonstration of his true insight into understanding the impact of their findings over 20 years before Peter and Rolf Zinkernagel were awarded the Nobel Prize. I owe the entire future direction of my career to this insight. Doherty joined Wistar in 1975 and in 1976 I joined the lab as his second doctorate student. Rita Effros was his first.

As one might imagine, immediately after such an important and groundbreaking discovery, it was an extremely fast-paced and exciting time working as a graduate student in Doherty's lab on anti-viral T cell immunity. Our primary focus was on T cell specificity and repertoire. Why were cytotoxic T cells specific for both virus and MHC? Were there two receptors or one? To address these questions, we naively began using an influenza virus system because of the known serological differences between virus strains. While we did not answer these questions during my time in the lab, we did discover the cross-reactive nature of the anti-influenza virus T cell response, helped to define positive and negative thymic selection during T cell development, and examined the role of cytotoxic T cells in protection from influenza virus infection. All of this was made possible by Hilary's insights into what was scientifically important and recognizing that Doherty was an incredible scientist.

Soon after graduation, I went to the Basel Institute for Immunology to spend two years as a member there before returning to Hilary's Institute; Peter Doherty returned to Australia to become the Department Chair at the John Curtin School of Medicine. For the next five years, first as an Assistant and later Associate Professor, I had the opportunity to interact with Hilary on many occasions at meetings and dinners. As anyone who had the privilege of being at Wistar during those years could tell you, it was a very unique place with many characters one will never forget, including Hilary. As has often been stated, he was truly a renaissance man and operated Wistar as his fiefdom.

One could tell many stories about their time at Wistar and about the people who worked there. Some would not be so flattering but many would certainly be funny. However, for many young scientists who trained at Wistar, one of the most enduring memories is the indirect impact of Hilary's scientific choices and insights that helped shape our careers.