Reflections of Parallel Journeys: A Career in Syphilis Research and the Rise of Women in STD Research

Title IX was enacted in 1972, stating that “No person in the United States shall, on the basis of sex, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any education program or activity receiving Federal financial assistance.” Although Title IX's impact is most visible in women's sports, women also began to be admitted to professional schools and graduate training in much greater numbers than ever before. I was one of those women. I graduated in 1973 with a B.A. in Biology from Revelle College of the University of California, San Diego–Revelle was the “science college” with an 8:1 male/female student ratio. Only one of my science lectures was given by a female professor. There were only a few female biology graduate students, but it was two of them who changed my life by suggesting that I consider graduate school. In fall 1973, I entered the Microbiology & Immunology PhD program at the University of California, Los Angeles, where I first became captivated by syphilis in Jim Miller's laboratory. There was a senior graduate student in the laboratory, Nancy Bishop, who showed me that a woman could succeed as a scientist, a wife, and a mother. In 1974, 2 years after Title IX was enacted, the Journal of the American Venereal Disease Association (now Sexually Transmitted Diseases) was launched. My 50-year career in syphilis research has paralleled both the growth of the journal and the growth in women as researchers in the field of STD. The inaugural issue of JAVDA listed 3 male editors, and all 22 members of the editorial board were men. Today, 50% of the Associate Editors are women, and 51% of the Editorial Board are women (Fig. 1).Figure 1: Percentage of male and female members of the JAVDA/STD editorial board, based upon rosters in the January issues of the indicated years.I had the privilege of being mentored by three amazing male scientific mentors: Jim Miller Ph.D., Stewart Sell M.D., and King Holmes M.D. Ph.D. They all imparted their knowledge and wisdom, and were strong advocates for my career development. All of them stressed independence, encouraged me to broaden my knowledge and scientific skills, gave me the freedom to pursue work that captured my imagination, and never made me feel that my gender was a barrier to success. Jim Miller had been trained in syphilis research by a woman, Dr. Ruth Boak, who was an early investigator of penicillin efficacy for syphilis. He encouraged me to read the old syphilis literature, instilling an understanding of the disease that guided much of my subsequent research. In the Miller laboratory, I demonstrated that Treponema pallidum, when opsonized by specific antibodies, could be phagocytized by macrophages, leading to my interest in defining the mechanisms of clearance of T. pallidum from early lesions. Stew Sell and I sat for hours at a 2-headed microscope, identifying lymphocytes and macrophages infiltrating early syphilis lesions, seeing the disappearance of T. pallidum, then the appearance of degraded T. pallidum antigens within the macrophages during healing. This led to our proposed model for clearance of opsonized T. pallidum by interferon-γ activated macrophages. At the University of Washington (UW), King Holmes taught me the importance of knowing the clinical aspects of syphilis to add medical relevance my research questions. When it was time to update the “Syphilis” chapter for Harrison's Principles of Internal Medicine, he invited me to be co-author and then sole author. I undertook a crash course in the literature of clinical syphilis. King and I sat side-by-side, walking through every sentence of the chapter, discussing nuances of wording and clarity of presentation—a wonderful learning experience! I and other women also sought support and mentoring from each other. In the STD community at UW, we would discuss our research, practice upcoming scientific talks, go on backpacking trips, celebrate new grants, commiserate about unfunded applications, and exchange baby clothes. We have supported each other through scientific successes and failures, weddings, births, divorces, illnesses, and deaths. Over the years, many women have thrived in the rich, welcoming STD and HIV research environment at UW and have held leadership positions in Seattle and elsewhere. Some of the “early women” (1980s) include, alphabetically, Connie Celum, Ann Collier, Denise Galloway, Ruth Greenblatt, Sharon Hillier, Grace John Stewart, Laura Koutsky, Joan Kreiss, Christina Marra, Jeanne Marrazzo, Dorothy Patton, Anne Rompalo, Jane Schwebke, Carol Spiegel, Pat Totten, Anna Wald, and Judy Wasserheit. These women have now trained other women. We also learned by watching other women who “mentored” simply by existing as exceptional role models. I distinctly remember, early in my career, seeing Sevgi Aral for the first time. She spoke eloquently and confidently, with such grace. I was in awe and, unbeknownst to her, she became a model for me. Although I have not achieved her eloquence and grace, she and I have had many wonderful conversations about women in the STD field and have worked together to champion other women, particularly regarding the Distinguished Career Award (formerly Parran Award). This award has been given nearly every year since 1972. In the 34 years until 2006, 32 awards were given, but only one to a woman: Genevieve Stout of the Venereal Disease Research Laboratory, in 1973. The subsequent multi-decade Parran glass ceiling was finally broken in 2006 when Sevgi Aral received the award, leading to better recognition by the ASTDA of the research and leadership contributions of women. Since 2006, nine other women have received the association's highest honor. This comment is not meant to disparage the many men who have received the award—they were all deserving but, in 2006, it was past time to also recognize outstanding women. My 50 years of research on T. pallidum and syphilis1 was spurred by the interests and expertise of my outstanding and wonderful trainees, to whom I owe so much. Christina Marra, a young neurologist starting an Infectious Diseases Fellowship, saw me in an elevator in 1988 and said, “King told me I should talk to you.” This meeting led to her outstanding career on neurological involvement in syphilis and HIV infections,2 and our decades-long collaboration and friendship. In the mid-1990s, Arturo Centurion joined the laboratory as a postdoc, bringing molecular biology expertise and initiating our interest in the Tpr family of proteins in T. pallidum. One of these, TprK, was shown to undergo antigenic variation,3 explaining the chronicity of T. pallidum infection. In 1996, Caroline Cameron, a postdoc, became interested in T. pallidum, beginning our long friendship and collaboration on syphilis vaccine development,4 and her own successful independent work on T. pallidum biology. Lorenzo Giacani arrived from Italy in 2002 as a PhD student and stayed, joining Arturo and me in studies of immune evasion and comparative genetics among T. pallidum subspecies and strains. Now on the UW faculty, he recently developed a system for genetic manipulation of T. pallidum,5 revolutionizing the study of syphilis pathogenesis. My final graduate student, Tara Brinck Reid, demonstrated that TprK antigenic variation facilitates development of secondary syphilis6 and is now beginning her academic faculty career at UW, defining the fine specificity of the cellular immune response in early syphilis with David Koelle. A half century after I began working on syphilis, I now see the STD field comprised of highly accomplished women and men in research, training, and leadership positions. Their achievements are reflected in each issue of today's STD. There is always more work for us to do to achieve equity and justice, but we have made huge advances in the past 50 years. I am privileged to have played a part.