Remembrances of Hilary Koprowski from a Surgeon's Perspective.

Hilary Koprowski was one of the medical giants that inspired my life and career—therefore the larger than life gratitude and affection I feel for him. Although this reality may color the remarks that follow, they are offered as my best personal recollections. I was introduced to Dr. Koprowski in the late 1970s by Dr. Michael Mastrangelo, an oncologist with a primary interest in melanoma at the Fox Chase Cancer Center, not long after I relocated there from the Surgery Branch of the National Cancer Institute. I had been working at the NCI as a senior investigator, primarily focusing on questions related to cryopreserving human lymphocytes as indicators of postoperative tumor status after immunotherapy or removal of tumors. Looking back, it is hardly believable how little I knew about lymphocytes at that time. These were the days when “tumor-specific antigens” as identified by polyclonal antisera were only beginning to be talked about, and considerable efforts were being made towards immunotherapy of melanomas at the NCI Surgery Branch. During this time, I had the opportunity to learn some of which I should have known earlier. Mike Mastrangelo and I had common interests, and I was still collecting sera from all manner of consenting cancer patients in the hopes that we might identify some indicator of a specific immune tumor response. Mike had heard about the amazing properties of a new creation, then called “somatic cell fusion products,” which were the monoclonal antibodies produced at The Wistar Institute under Hilary Koprowski's direction. He then made the introduction that was to be transformative for me. (1–3) Hilary Koprowski was a master at transferring enthusiasm. He knew how to communicate to those less informed, such as myself, the potential of the new technology and its revolutionary use in identifying and defining complex macromolecules. This approach was viable not just for those mediators of human biology and my interest in malignant disease, but for countless other uses as well. Hilary was well acquainted with the concerns of clinical surgeons who cared for cancer patients and the need for alternative therapeutic modalities that could be added to local or regional approaches to human cancers. Chemotherapy was at that time not the answer for many. Koprowski rightfully recognized the potential for these exquisitely specific reagents to identify and treat distant metastases that were undermining local therapeutic modalities. I do not believe that he coined the term “magic bullet” that was pinned on monoclonal antibodies in those years, but he shared the desire to give these reagents the broadest evaluation for their potential benefit in the therapeutic armamentarium. A steep learning curve was facilitated by many investigators at The Wistar Institute, and I became convinced that monoclonal antibodies were the answer to the shortcomings of the antisera we previously used to identify tumor-specific antigens, which could now be identified as individual molecules. Those scientific investigators, including Dr. Zenon Steplewski and Drs. Meenhard and Dorothy Herlyn, also introduced me to a level of scientific investigation that was greater in magnitude from what I had previously experienced. They taught me that there were fundamental differences between a scientific investigator and a clinical one, a combination that made, at that time, a fruitful partnership. Many laboratory doctors expected human patients with malignant disease to react to interventions as would an inbred strain of rodents. They also did not appreciate the variability of what was included under one label of a specific human disease, for example, “breast cancer. ” The fact that all adenocarcinomas of the breast were not the same, as far as its behavior in a human was concerned, was new information to many. So we each occupied a position of ignorance, and we found the partnership compensated for this to some degree. During this time, a great number of monoclonal antibodies (MAbs) against a variety of human and viral tissues were generated and characterized at The Wistar Institute. Numerous investigators were using these reagents to define many mediators of metabolic processes involved in those human conditions that could be studied in vitro. The most interesting of these antibodies for the clinical surgeon were a few that had been created from a human gastrointestinal track adenocarcinoma. Drs. Steplewski, Herlyn, and Herlyn had made extensive evaluations of monoclonal antibodies raised in response to a human colonic adenocarcinoma. They also had demonstrated in vitro killing of these human tumors in cultures and in a nude mouse system. (3,4–6) The MAbs that had shown specific responses when tested in vitro were used as potential tumor markers in very preliminary studies. The carcinoma embryonic antigen (CEA) had been used in clinical medicine for about a decade, but it had many of the failings that these new reagents hopefully would overcome; therefore the CA19-9 antigen, a monosialoganglioside associated with gastrointestinal tumors, had a higher specificity. (7,8) Because of this team's preliminary work with two of these antibodies, one with cytocidal activity, another with binding characteristics to sera from tumor-baring animals, there was considerable enthusiasm to expose these reagents to trials on human material.