Walter Elmore Nance (1933–2021)

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My father, Walter Nance, died on October 17, 2021, having completed a long, productive, and influential career in human genetics and a happy life filled with long-standing relationships with the colleagues and students he inspired with his questions and enthusiasm.

Chronology

Dr. Nance—for all that he could drink airag and roust about the poker table familiarly with anyone who would enter his sphere (more about that later), he preferred the more formal “Dr. Nance” to “Walter” until he had been introduced—was born in 1933 in Manila, the Philippines, where his father, Dana Nance, was serving as a quarantine officer in the Public Health Service. The family soon moved to Shanghai, China, where the elder Nance, a surgeon, set up a practice with his physician brothers. With World War II inevitable in 1941, the future Dr. Nance, his two siblings, and his mother returned to his mother’s ancestral home in New Orleans, LA. Dana Nance was sequestered in a Japanese internment camp first in Baguio and then Los Baños, the Philippines, from 1941 until his liberation in 1945. The reunited family moved to Knoxville and then Oak Ridge, TN, where Dana Nance opened a surgical practice. After a couple of years in the local high school, Dr. Nance graduated from Phillips Exeter Academy in Exeter, NH, in 1950, and then returned to Sewanee, TN, to study mathematics at University of the South. He entered the Harvard Medical School class of 1958, prepared to return to Tennessee to practice clinical medicine. However, a fateful life-determining moment occurred during a summer externship back home after his second year. Observing physician and family friend, Dr. William Pugh, delivering a set of twins, he innocently asked, “How can you tell if they are identical or fraternal?” Dr. Pugh rejoined, “Why don’t you find out for yourself?”

With that single question, Dr. Nance’s career trajectory was set. The first of about 250 papers over his 54-year publication career, “On gemellology,” was published in 1959.¹ After Harvard, he moved to Nashville, TN, to begin an internal medicine residency at Vanderbilt and, with his wife, Carol (Smith) Nance, began his own personal experiment in genetics: the births of his two children. Dr. Nance was encouraged by department chair David Rogers to pursue his interest in genetics, so in 1961, he moved to Madison, WI, where he studied the genetics of glucose-6 phosphate dehydrogenase as the first post-doctoral trainee of future Nobel laureate Oliver Smithies.^2,3 He returned to Vanderbilt in 1963 and was awarded a prestigious 5-year Markle Scholarship in 1964. Dr. Nance remained on the faculty in internal medicine there until 1969, when he became an associate professor in the department of medical genetics at Indiana University. In 1975, at age 42, he moved to Medical College of Virginia (MCV; now known as Virginia Commonwealth University School of Medicine) as professor and chairman of the department of human genetics, a position he maintained until his retirement in 2002. After a divorce in 1987, he reconnected with, and in 1992 married, a fellow childhood expatriate from his Shanghai years, Mayna (Avent) Nance. After retirement, he and Mayna returned to her home in Sewanee until Mayna’s death in 2020.

Academic contributions

Dr. Nance’s career was that of the quintessential physician-scientist. His work in Madison utilized the protein-separating starch gel electrophoresis procedure that his mentor, Oliver Smithies, had invented a few years earlier. At Vanderbilt, he described the clinical aspects of several cytogenetic disorders along with cytogeneticist Eric Engel. During this time, Dr. Nance also developed a lifelong interest in hereditary deafness, working with Anne Sweeney, Freeman McConnell, and others at what is now the Vanderbilt Bill Wilkerson Center for Otolaryngology and Communication Sciences to describe syndromic and nonsyndromic forms of deafness. He served as co-investigator on an NIH-funded Hereditary Deafness Study Group at Vanderbilt from 1966–1971, during which time he described X-linked conductive deafness with fixation of the stapes (Nance deafness)⁴ and a recessively inherited chondrodystrophy, oto-spondylo-megaepiphyseal dysplasia (Nance-Sweeney syndrome).⁵ Another X-linked syndrome, Nance-Horan syndrome, followed in 1974.

Following his move to Indiana, Dr. Nance combined his mathematical training and clinical skills with his long-standing interest in twins to develop a mathematical model for the study of twins and their offspring, which he first described, with Dr. Linda Corey, in 1976.⁶

By the time Dr. Nance moved to Richmond in 1975, his bidirectional academic paths were set. Generations of trainees over the next 3 decades attended Saturday morning Twin Clinic, collecting an enormous amount of data leading to multiple publications and a 20-year collaboration with the Norwegian Twin Registry, led by Kåre Berg.

The strength and productivity of the Virginia Twin Registry, and Dr. Nance’s interest in statistical modeling, lured the late Lindon Eaves (1981–2013) and, for a brief time, his former student, Nick Martin (1983–1986), to join the faculty at MCV.⁷ Ken Kendler, a psychiatric geneticist, arrived in 1983 and, with colleagues Eaves, Andrew Health, Michael Neale, and others, continued to develop and study large datasets with a particular interest in behavior and psychiatric disorders.

After a sabbatical year in a molecular genetics laboratory at the Rockefeller Institute in the early 1990s (my father with a pipette?), Dr. Nance returned to Richmond with renewed enthusiasm for unraveling the molecular genetics of hereditary deafness. Along with geneticist Arti Pandya, former students Kathy Arnos and Susan Blanton, otolaryngologist-geneticist Xue Liu, and a host of collaborators, he published studies on over a dozen forms of hereditary deafness between 2000 and 2013.

A peak experience late in Dr. Nance’s career was a set of trips he took to Mongolia, where he and his team visited the school for the deaf in Choibalsan, along with collaborators from Ulanbaatar. This ultimate field trip included broken-down jeeps, nights spent in yurts, the eating of a large amount of lamb and drinking of the aforementioned airag (fermented yak milk), and resulted in publications on deafness in Mongolia due to mutations in connexin 26 and in the 12S RNA mitochondrial gene.⁸

Chairman of the department of human genetics

Dr. Nance was the chairman of the department of human genetics at MCV from 1975 until his retirement in 2002. During that time, he created a solid environment for clinical and research activities in human genetics, bringing to the department Drs. Judith Brown (cytogenetics), Barry Wolf (biochemical genetics), and Joann Bodurtha (clinical genetics), who, along with Linda Corey in genetic epidemiology, anchored his four priority areas. His wife Carol supported the department’s growth through her varied talents as a scientist running the department’s amino acid analyzer, an editor and spell-checker of manuscripts and grants (Dr. Nance was a notoriously creative speller), a supportive ear for students, and host of departmental social activities. At least sixty students completed PhDs during his tenure, and approximately an equal number completed master’s degrees in genetics or genetic counseling. Graduates of the program include Drs. Gerald Feldman (2015 President of the American College of Medical Genetics) and Cynthia Morton (2014 President of the American Society of Human Genetics; ASHG), among many other leaders. By the time of Dr. Nance’s retirement in 2002, the department had eighteen faculty and a dozen adjunct faculty.

National and international leadership

Dr. Nance served twice in leadership roles within ASHG, first as secretary (1971–1973, at a time when serving as secretary meant that one’s wife typed addresses on envelopes for mailings, while one’s children stuffed the envelopes; this stint also provided the opportunity for my first contribution to the organization, the design of the front cover of the 1973 directory!), and on the board of directors from 1991–1994 (president in 1992), at the time of the then-controversial splitting off of accreditation for genetic counselors from doctorate-level specialists, which led to the formation of the National Society of Genetic Counselors⁹ (Figure 1). He was a founding member, vice president, and then president of the International Society for Twin Studies (1980–1986). He served on the Board of Directors of the American Board of Human Genetics (and Genomics) from 1982 to 1986, serving as vice president and then president during that time. He received the Virginia Commonwealth University Award for Excellence in Teaching, Service, and Research in 1985 and the ASHG McKusick Leadership Award in 2007.¹⁰

Figure 1.

A gathering of ASHG presidents at the 2011 annual meeting

Back row: Stephen Warren, David Rimoin, and Walter Nance. Front row: Kurt Hirschhorn, Roderick McInnes, Judith Hall, Lynn Jorde, and Robert Nussbaum.

Humanism and legacy

Dr. Nance delved occasionally into the psychosocial and ethical aspects of genetics. He was particularly interested in assortative mating and reproductive fitness within the deaf community and more broadly in the deaf community’s perception of deafness as a handicap—or lack thereof. His team’s survey showed that, whereas hearing members of the deaf community (e.g., hearing parents of a deaf child) had a strong preference to have a hearing child, deaf members of the deaf community either preferred to have a deaf child or had no preference.¹¹

One could wonder whether his interest in the perception of disability by the “disabled” person relates to his own disability, of which he never spoke and for which he never sought any kind of sympathy, exemption, or compensation: as a child in New Orleans, he contracted polio, and came out of the experience with a largely nonfunctional left arm. Interestingly, although neither he nor anyone around him considered him disabled, when I asked him a year before his death, at a time when he had difficulty remembering most anything, if he had any regrets over his lifetime, without a moment’s hesitation, he said, “swimming in the Mississippi River.”

In the end, one is judged by the people one leaves behind and by their achievements. Although, at a memorial Zoom meeting after his death, most former students recalled being “Nanced,” referring to his tendency, just as the student thought they had completed their experiment, manuscript, or thesis, to ask, “Why don’t you run this experiment, re-analyze that dataset, ask this other question, before you send it in?”, they also recalled their graduate student or fellowship time with fondness and a strong feeling of camaraderie. More than one student said, “He saw something in me that I didn’t see in myself,” or recalled, “I’m not sure why he picked ME to go on that particular field trip, but I’m so glad he did because it changed my life.”

His “Advanced Probability Seminars” were a mainstay of the annual ASHG meetings for many years, this being a euphemism for a cutthroat poker game and reunion of MCV and Indiana University geneticists and anyone else brave enough to be in the room.

What is Dr. Nance’s legacy? I believe that he created an environment for the study of human genetics that was inclusive, optimistic, and youthful, where ideas were welcomed and strange experiments of nature could lead to a career path. His 54 years of scientific work involved about 500 co-authors, many of whom were lifelong friends. We could do well in our increasingly constrained 21^st century world to remember the joy of being inclusive just because we want to be, not because our institutions or governments require us to be, and to allow new ideas to bubble forth even if they start out inelegant and messy, without forcing them through our increasingly rigid funnels of pre-written checklists, algorithms, and political correctness. When was the last time you went on a field trip, made a house call, or even looked up from your computer? As a student of human genetics, Dr. Nance never forgot that those things he was studying, whether they were spreadsheets, starch gels, audiograms, or whole exomes, came from people (Figure 2).

Figure 2.

Walter Nance at age 87, still inquisitive

Try using his favorite word the next time a student asks an odd unanswerable question, someone hands you a mug of airag, your grant proposal gets a reasonable score just shy of the funding range, or your paper gets accepted to the journal: “Fantastic!”