In Memoriam
Wendy L. Havran, Ph.D., AAI ’85
1955–2020
In the wake of the January 2019 passing of long-time and devoted AAI member Wendy Havran, the following remembrance was authored and kindly submitted for AAI publication by Adrian C. Hayday, Ph.D. (AAI ’91), Kay Glendinnig Professor and Chair, King's College London School of Medicine. AAI gratefully acknowledges the elegant tribute and is pleased to share it with Wendy’s many colleagues, collaborators, and admirers within immunology and beyond.
In the enshrouding darkness of a gloomy mid-winter evening in England, I learned in disbelief of the death that morning of a long-standing friend and deeply admired colleague, Dr. Wendy Havran, who had suffered a fatal cardiac arrest following an acute illness. Before the night was out, it seemed that the whole world was on a single time zone as outpourings of shock and sadness and condolence flooded in from all points of the compass. Such was the respect that Wendy commanded for her iconoclastic scholarship, her elegant experimental studies, her training and mentorship, and for simply being such an effortlessly kind person. There was instant recognition that the immunology community had lost a stand-out figure, a loyal advocate, and a dear friend.
Wendy was born on September 1, 1955, in Houston, Texas, in what is today the most diverse city in the United States. Perhaps that very environment opened Wendy’s mind to a world beyond the straight and narrow, and to a capacity for thinking differently that underpinned her many ground-breaking contributions to immunology.
From Houston, Wendy gained a scholarship to Duke University, where she was awarded a B.S. in zoology in 1977. Staying at Duke, she immersed herself in immunology, initially with John Cambier (AAI ’78), a recently appointed assistant professor. She was instantly successful and prodigiously productive, combining a rare talent for careful experimentation with a confidence to chart new territory. The identification of the T cell receptor in the early 1980s had proved galvanising for the study of T cell biology and development, within which the significance of T cell subsets was a major unresolved issue. As a Ph.D. student with Frank Fitch (AAI ’61) in Chicago, Wendy showed that cytolytic activity segregated with the specificities of CD8 (Lyt-2)-expressing T cells, and away from those of CD4 (L3T4)-expressing cells.
That study in 1987 was the first of four first-author Nature papers to appear over the course of just three years, the remainder being with Jim Allison (AAI ’78), whose laboratory at Berkeley she joined for postdoctoral studies. To each of those Nature papers, Wendy was irrefutably the major experimental contributor, individually and courageously pursuing a breadth of challenging techniques that reflected the times: there were no kits; there were very few teams of 20, and science was pursued as a personal quest, reflecting deep-set curiosity and conviction. In Wendy’s case, that conviction was soon focussed on the newly discovered, entirely unanticipated, gamma delta (γδ) T cell compartment.
In Jim’s lab, Wendy’s efforts to distinguish the biologies of αβ and γδ T cells had produced an immunological icon: the successive waves of development of discrete γδ T cell subsets preceding the emergence of αβ T cells. That iconic figure (Figure 3 of her third Nature paper), or variants thereof, continue to this day to be shown as the backdrop for scores of studies, a habit I fully expect to be repeated at future ThymUS meetings. Moreover, Wendy had quickly built upon her findings to show that the earliest wave of progenitors originated uniquely in the fetus, from where the cells went on to compose the tissue-resident dendritic epidermal γδ T cell compartment that had been recently described by Tigelaar and by Sting and their respective coworkers.
It is important to note that Wendy’s results arrived into a world where immunology was a science of circulating cells that received their instructions in secondary lymphoid organs and could be repopulated by adult bone marrow reconstitution. From every standpoint, her iconic figure was iconoclastic: it preceded by over 20 years the much-lauded classification of macrophages as either fetal or bone marrow derived, and by about the same margin it prefaced the intense contemporary interest in tissue-resident memory T cells.
Most deservedly, Wendy had been awarded a prestigious Lucille P. Markey fellowship that provided a springboard for her appointment in 1991 to a junior faculty post at the Scripps Research Institute. In a heady and competitive environment spilling over with immunological talent, she continued to chart new and unique territory. In 1994, at a time when T cells were broadly distinguished by whether they produced IFNg or IL4, Wendy and Richard Boismenu reported in Science that skin and gut intraepithelial γδ T cells produced factors that directly promoted epithelial cell growth, and set the course for Wendy’s subsequent studies with Julie Jameson showing that dendritic epidermal γδ T cells made profound contributions to wound healing. Seriously unappreciated by many at the time, those studies were silo destroying, firmly crossing over into epithelial cell biology and allowing immunology to find its place within the pathophysiology of host tissues. And the impact did not stop there. Almost a decade ahead of contemporary interest in how local tissues shape immune responses, Wendy, together with Deborah Witherden and their colleague Ian Wilson, identified novel molecular axes demonstrating that T cell co-stimulation could originate in the epithelium, as much as in myeloid antigen-presenting cells.
It was in recognition of this litany of scientific contributions that Wendy had been selected to present one of the AAI Distinguished Lectures at IMMUNOLOGY2020™.
Of course, Wendy’s work was particularly impactful in the γδ T cell community, where she was universally loved and respected. She was an untiring advocate of the cells’ uniqueness and importance, a perspective that her work unquestionably supported, and she showed perennial warmth to those who studied them, as evidenced by many generous “News and Views” essays about others’ work. She unfailingly sought funding for conferences and meetings, as testament to which the International γδ T cell Conference series has become unfailingly successful. It is hard to conceive of her not being there in the future, but her legacy will be her remarkable findings. One after another, they have mapped out a new immunological territory for a next generation to pursue, to elucidate, and hopefully to exploit for clinical benefit.
That “next generation” was always close to Wendy’s heart. Beyond the inspiration provided by her own experimental accomplishments, Wendy warmly offered her time and guidance to countless individuals, openly declaring mentorship to be her favourite part of her job. She was associate dean of the Skaggs Graduate School of Chemical and Biological Sciences and among her honors was named the 2018 Outstanding Mentor by the Society of Fellows, a postdoctoral organization of the Scripps Research Institute. Her laboratory was a training ground for postdocs, Ph.D. students, undergraduates, and secondary and high school teachers. She sat on numerous thesis committees and skilfully ran the NIH-funded graduate training grant for many years. In 2002, Wendy established the Scripps Research’s Summer Immunology Internship Program for undergraduates interested in pursuing Ph.D. studies in immunology, and over the years continued to help numerous organizations, including the Scripps, UCSD, and the AAI, with a variety of different training programs and activities.
It has been said that an effective mentor understands that his or her role is to be dependable, engaged, authentic, and tuned into the needs of the mentee. Wendy understood the time required of becoming engaged and tuned in. Ralph Budd wrote that while he was a postdoc at Stanford and collaborating with the Allison lab in Berkeley, Wendy was always highly collaborative and very willing to exchange information and opinions. To her credit, Wendy was also acutely aware that time could be a precious commodity for some, particularly women confronting the balance of family and professional demands. Her response was to find every way to help, be it through personal counsel or service on the AAI Committee on the Status of Women, and for those efforts she is particularly admired.
In the course of her endeavors helping others, Wendy found a ready ally in her disarming humour. I recall when she and I were invited to Japan as keynote speakers for the Society of Mucosal Immunology annual meeting. We arrived at the SMI welcoming cocktail party only to find out that we were each expected to deliver an address at that event as well. Concerned that we had about 10 minutes’ notice of this, I approached Wendy to find her surprisingly composed. “Well,” she said, “I told them ‘Scripps Institute, North Torrey Pines Road, La Jolla’”!
Of course, she went on to deliver a beautifully articulated, simple, and sincere “thank you” for the honour bestowed on us, and a pledge of friendship and help for any in Japan seeking to gain experience abroad.
Such was Wendy: an extraordinarily accomplished scientist, a peerless mentor, and simply the kindest person. It is to her memory that this year’s AAI Distinguished Lecture presentations are fondly dedicated. She is much missed, particularly in the γδ T cell community, but her pioneering mapping out of body surface immunology is a genre to celebrate and to build upon.