Philip A. Brunell, MD: Remembering a Pioneer of Varicella Research

The House That Ruth Built, the famous Yankee Baseball Stadium, was constructed in the Bronx borough of New York City in 1923. Babe Ruth played there for another decade. Phil Brunell was born on February 1, 1931, and raised on Townsend Avenue in the Bronx during the Great Depression. As a child, he often helped out at his dad’s pharmacy, sometimes working as a soda jerk. Although he never saw Babe Ruth play baseball, he was heavily influenced by America’s pastime. Phil played stickball with the other boys on the streets of his Bronx neighborhood. A broom handle was the bat, a rubber ball replaced a real baseball, and a manhole cover served as home plate. Phil was always a competitive player. On special occasions, trips were made a mile south to Yankee Stadium to watch a professional ballgame. After completing high school, Phil considered joining a Yankee’s minor league baseball team, fulfilling his childhood dream. However, with lingering memories of the Great Depression, Phil entered City College, where he played on the varsity baseball team. His college years were followed first by a brief stint at graduate school, then a transition to medical school and a pediatrics residency at the State University of New York at Buffalo from 1953 to 1960. With the passing of Philip Brunell on January 29, 2023, the infectious diseases community lost a physician-scientist whose work led to the first preventative measures for varicella infection. This remembrance is the story of his life-long passion for varicella research and the colleagues he trained along the way.

Because of interests in infectious diseases piqued during his residency, Phil began his professional career as an officer in the U.S. Public Health Service in 1961, based at the Centers for Disease Control in Atlanta, studying and developing serologic tests for measurement of antibodies to varicella-zoster virus (VZV) [1]. In 1964, he joined the Department of Pediatrics at New York University where he used his newfound laboratory skills to find that neonates, whose mothers had varicella within a week before their birth and were treated with gamma globulin but had undetectable levels of VZV antibody, developed neonatal varicella; in contrast, one neonate who did have detectable antibody did not develop the disease [2]. Thus, he reasoned that a product enriched for VZV antibody might be effective to reduce varicella. Subsequently, Phil published a landmark paper in 1969 showing that varicella could be prevented in healthy children with the use of zoster immune globulin [3]. One of us (A.A.G.) was Phil’s first fellow in pediatric infectious diseases at the New York University School of Medicine. Women often were not warmly welcomed in medicine at that time, but Phil was an outstanding mentor who was very supportive of women in medicine. In 1974 Phil performed a follow-up study with one of us (A.A.G.) and showed that prophylactic administration of zoster immune globulin in children with leukemia and other malignancies prevented varicella [4]. At the same time, Phil and A.A.G. developed a highly sensitive fluorescent antibody to membrane antigen test which was crucial for assessment of varicella vaccine effectiveness in clinical trials in the United States [5].

In the early 1970s, Michiaki Takahashi developed a live attenuated varicella vaccine in Osaka, Japan, and showed that it could prevent varicella. Debate ensued in the United States about the use of such a vaccine with concerns about delaying the onset of varicella, a possible increased risk of zoster later in life of persons already infected if varicella was eliminated, and the safety of giving a live virus vaccine that would remain latent in the body. In 1979, an important consensus conference was organized by the National Institutes of Health (NIH) and Phil was among the leaders promoting clinical trials of the new varicella vaccine in the United States.

Phil moved in 1975 to the University of Texas Health Science Center at San Antonio as Chief of the Division of Pediatric Infectious Diseases as well as Chair of the Department of Pediatrics (Figure 1). One of us (C.G.) was recruited by Phil as an assistant professor and worked with him on studies of antibody responses to VZV in immunocompromised children as well as studies to define replication of the virus in cell culture. After a year in the laboratory, Phil kindly sponsored an NIH FIRST (First Independent Research Support and Transition) award for C.G. Subsequent NIH-supported research efforts at San Antonio were successful [6]. Phil established a pediatric infectious diseases fellowship program and recruited talented pediatricians who transitioned to successful careers in academia. These included Betty Edmond, Kristen Weigle, Ziad Shehab, Alan Lievens, Jean Wiedeman, and Vas Novelli. Phil relished his time with the fellows above all other responsibilities in the division. With their assistance, Phil showed that the live attenuated varicella vaccine was safe and highly effective in preventing varicella in children with acute lymphoblastic leukemia [7]. The last-named fellow has become the Lead Infectious Diseases Consultant at the Great Ormond Street Hospital for Children in London.

Figure 1.

Philip Alfred Brunell, 1931–2023. The academic journey of Dr Brunell included stops at Atlanta, New York City, San Antonio, Los Angeles, and Bethesda.

Phil’s departmental leadership style was traditional, with a reliance on the division directors. Under Phil’s direction, the department sponsored a big social event each year to welcome new house staff and new faculty. During one of his early years in San Antonio, he held a picnic for the new personnel on a particularly warm Saturday in July. With his enthusiasm for baseball maintained since his New York days, he organized a softball game between faculty and house staff. Phil played his favorite position as a shortstop. But after 2 innings, the majority of the players told Phil that it was too hot in Texas in July to play any ball game. Game canceled; everyone headed back to the park pavilion for a lunch catered by the still popular Bill Miller Bar-B-Q Restaurant. This vignette illustrates an unplanned humorous episode in the academic sojourn of Phil Brunell.

Phil subsequently was recruited by the Department of Pediatrics at Cedars-Sinai Medical Center in Los Angeles in 1990, where he continued to champion the use of viral vaccines. While living in Los Angeles, Phil was able to attend a few games played by the Los Angeles Dodgers baseball team. Earlier in his career, Phil had seen the Dodgers play at Ebbets Field, their Brooklyn ballpark before the team left New York for Los Angeles in 1957. However, when an unexpected opportunity arose in 1995, Phil transitioned from Cedars-Sinai Medical Center to the Laboratory of Clinical Investigation at the National Institute of Allergy and Infectious Diseases in Bethesda, where he worked with Stephen Straus and one of us (J.I.C.). Phil was excited to return to a VZV research laboratory after his lengthy prior administrative positions and with youthful enthusiasm he learned the newest experimental protocols. Perhaps of even greater importance, Phil was thrilled to become the first NIH recipient of the live attenuated zoster vaccine in the double-blinded and placebo-controlled Shingles Prevention Study. The NIH Public Affairs Office in turn took his photograph and forwarded a blurb to the New York Times. Certainly, he was proud that Zostavax® was yet another formulation of the live varicella vaccine (Varivax®; Varilrix®) first produced by his close colleague Professor Takahashi. Furthermore, Phil’s reward for 4 decades of VZV scholarship was co-authorship on the 2005 paper already cited 2796 times [8].

The three of us are pleased to be the second-generation academic legacy of Phil Brunell. Sometimes with a smile, Phil would reflect upon the quotation attributed to Woody Allen (a variation on a quotation from Thomas Edison) that 90% of success in life is just showing up (Figure 1). In turn, at the NIH, Columbia University and the University of Iowa, the three of us have trained numerous graduate students, residents, and postdoctoral fellows who comprise a third-generation of virologists, many with an interest in further basic and translational VZV research. Along with his three children, we celebrate Phil’s accomplishments as we conclude this Remembrance with a baseball metaphor: Phil showed up for the game.