Leadership in Sexually Transmitted Infections Research and Training: The Legacies of King Holmes

Contemporaneous with the early years of Sexually Transmitted Diseases, the 1970s and 1980s saw the rapid evolution of sexually transmitted infection (STI) science and research, which previously had been dominated by clinical observation and anecdotes, to embrace modern microbiology, immunology, epidemiology, and the behavioral and social sciences. King Kennard Holmes, MD, PhD, is a visionary who saw the need and, during his nearly 6 decades at the University of Washington (UW), blazed a path as the most effective proponent of this historic transition, arguably the single most productive investigator, and its most influential driver. King's STI research career began during his US Navy service—when he also earned his PhD degree—and focused on gonorrhea and nongonococcal urethritis (NGU). His first 3 STI-related peer-reviewed research publications reporting that work were published simultaneously in the Journal of the American Medical Association—on the clinical epidemiology and treatment of NGU and antibiotic-resistant gonorrhea. His early research at UW addressed the microbiology of Neisseria gonorrhoeae; the clinical manifestations, epidemiology and public health impacts of gonorrhea, including the first modern studies of pharyngeal infection; disseminated gonococcal infection; asymptomatic urethral infection; the distribution of infected anatomic sites in persons with gonorrhea; and antibiotic treatment. King's research on gonorrhea continued for more than 40 years. Long before its time, King designed and conducted the first study that foreshadowed antibiotic prophylaxis to prevent bacterial STI: a single 200-mg dose of minocycline proved effective for preventing gonorrhea after sexual exposure to partners at risk, a concept now being widely implemented 5 decades later as doxy-PEP. With his trainees and a rapidly growing and diverse panoply of colleagues, he expanded efforts into clinical aspects and epidemiology of Chlamydia trachomatis and Ureaplasma urealyticum infections, including their roles in the etiology of NGU and mucopurulent cervicitis, the microbial ecology of the vagina, and the first studies of the clinical manifestations and treatment of bacterial vaginosis. At about the same time, he and his trainees began to investigate the clinical spectrum and epidemiology of genital herpes and the herpes simplex viruses and the first systematic studies of STI in men who have sex with men. His interests further expanded to the clinical aspects of syphilis, as well as the importance of STI pathogens in the urethral syndrome in women. The 1990s also saw King and his trainees engrossed in the natural history and epidemiology of human papillomavirus infections, their etiologic role in cervical and other cancers, and testing of the HPV vaccine. Early on, through assembly of teams of accomplished, multidisciplinary UW investigators who became leaders in their own right, and increasingly with diverse colleagues in other institutions, he led rigorous studies of the etiologies and manifestations of major STI syndromes such as NGU, mucopurulent cervicitis, proctitis and proctocolitis among men who have sex with men, epididymitis, pelvic inflammatory disease, and STIs as determinants of pregnancy outcomes. This team approach provided more complete understanding than could be achieved by single investigators or within any one academic domain, in a way that expanded appreciation of the import of these syndromes and radically changed clinical STI management across the board. In addition to nearly 600 scholarly publications, King authored or edited numerous books, most prominently 4 editions of the iconic textbook in our field, Sexually Transmitted Diseases. With the global HIV/AIDS pandemic, King became immersed in shaping the international response to this public health crisis, forging new collaborations with international partners. With his trainees and innumerable other colleagues, he worked to define the extent of HIV infection in sub-Saharan Africa and elsewhere, and later to test and implement treatments and prevention strategies. His efforts included training international clinicians and scientists to conduct well-designed and impactful research with unequaled commitment to local capacity building, exemplified later by his appointment as founding Chair of the UW Department of Global Health. Perhaps King's greatest source of professional pride and his most enduring legacy is his commitment to training the next generations of STI investigators, clinicians, and program experts through direct mentorship, development of STI and HIV training programs, and his unwavering advocacy and championship of both young and mature investigators. Those trained by King and following generations of his own trainees comprise 32 (53%) of the past 60 recipients of ASTDA's Distinguished Career and Achievement awards, and a third of the authors of the articles in this anniversary issue of the journal. We 3 benefitted immensely—both professionally and personally—from King's mentoring during the early years of his career and ours, when we would spend hours sitting next to him as he read our manuscript drafts, parsing every word to make the language precise and clear (Fig. 1). As his travel schedule grew, advice and mentoring were at times dispensed as we drove him to the airport for his next flight! These experiences were punctuated by relevant anecdotes and advice about potential projects and collaborations—but most important, by his extraordinary insights and intuition, which drove the standards for design and interpretation of STI research. Among King's many awards are the ASTDA Distinguished Career Award (then the Thomas Parran Award) in 1983, after only 16 years in the field; the Bristol-Myers Squibb Infectious Diseases Research Award (1992–1997); election to the Institute of Medicine (1987); and the Canada Gairdner Foundation Global Health Award in 2013 (Fig. 2). The King K. Holmes Professorship in STDs and AIDS was endowed at UW in 2014.Figure 1: King Holmes co-writing an early research paper ca. 1973.Figure 2: King Holmes on the occasion of the Canada Gairdner Foundation Global Health Award, 2013.King recognized the dire state of professional training of physicians in STI and saw the future of STI science not only in the biomedical domains and across virtually all medical specialties, but also epidemiology and the behavioral and social sciences. Joined by his early mentees, King developed a multidisciplinary training program at UW, supported by an NIH training grant. This training program, currently in its 47th year, has supported 185 postdoctoral (MD and PhD) and 83 predoctoral (pre-PhD) fellows. Countless other trainees, supported by several funding sources, also have benefitted from the program's structure, housed since 1989 in the UW Center for AIDS and STD. Trainees include infectious diseases specialists, gynecologists, neurologists, microbiologists, geneticists, epidemiologists, and sociologists; 3 directors of CDC's Division of STD Prevention; director of the National Institute of Allergy and Infectious Diseases; chief of NIAID's STD Branch; heads of several academic divisions of infectious diseases; directors of municipal, state, and national public health agencies and STI/HIV programs; and presidents and other officers of the International Society for STD Research, the International Union against STI, and the Infectious Diseases Society of America. Space precludes naming them all. With apology to the many not mentioned, a partial list of “graduates” of King's direct mentorship is a who's who of past and current leaders in the field of STI and HIV, including (alphabetically) Sevgi Aral, Bob Brunham, Elizabeth Bukusi, Connie Celum, Craig Cohen, Ann Collier, Larry Corey, David Eschenbach, Patricia Garcia, Matt Golden, Ruth Greenblatt, Sharon Hillier, Grace John Stewart, Bob Jones, Joan Knapp, Laura Koutsky, Joan Kreiss, Lisa Manhart, Jeanne Marrazzo, Dave Martin, Jorma Paavonen, Dorothy Patton, Peter Piot, Tom Quinn, Anne Rompalo, Jorge Sanchez, Eric Sandström, Jane Schwebke, Carol Spiegel, Walt Stamm, Brad Stoner, Pat Totten, Judy Wasserheit, and Paul Wiesner. Most of these, in turn, have trained further generations of accomplished STI professionals. The list of King's colleagues and research collaborators other than trainees would be even longer and include still more renowned in our field. We have been honored to write this tribute to King. His commitment, energy, generosity, and vision have changed our lives and the lives of innumerable people, most of whom have never had the privilege of knowing him. All persons who value sexual health and the professionals working to foster that goal owe him a profound debt of gratitude. He has indeed changed the world.

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