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Purnell W. Choppin (1929–2021)

2021; Wiley; Volume: 35; Issue: 12 Linguagem: Inglês

10.1096/fj.202101575

1530-6860

CLAIRE HUMMEL WINESTOCK,

Viral Infections and Outbreaks Research

In 1968, I sat before my desk at the U.S. National Institutes of Health (NIH) as the new Executive Secretary of the Virology Study Section (VRSS) and found some notes sent to my predecessor recommending Purnell Choppin (Figure 1) as a future reviewer for the VRSS, but with advice that, at present, he was too young. Then, in other papers, I discovered that the caution had been ignored, and Purnell was a new study section member. I met him at the next meeting, and thus began my long and rewarding working association with him. During his 4-year term, Purnell, despite his relative youth, proved to be one of the stalwarts of the group: thoroughly prepared, knowledgeable, even-handed, and tendering carefully considered recommendations. He was respected by all. Several years after his term had ended, he agreed to return as Chair and skillfully guided the reviewers through a 3-year period with his smile, calm voice, and exactly the right words. Purnell Whittington Choppin was born July 4, 1929, in Baton Rouge, Louisiana, to Arthur R. and Eunice Bolin Choppin. His mother was a high school teacher, and his father was Professor of Chemistry and Dean of the College of Chemistry and Physics at Louisiana State University (LSU; Baton Rouge, LA, USA). Purnell received his MD degree in 1953 at the LSU School of Medicine. He served a residency at Barnes Hospital (St. Louis, MO, USA) and then military service as a medical officer in the U.S. Air Force, primarily in Japan. When he returned from military service, Purnell decided to turn his efforts from the practice of medicine to biomedical research, specifically to virology. He joined the laboratory of Igor Tamm at the Rockefeller University (New York, NY, USA) as a research fellow and later was appointed to the faculty. Purnell arrived at Rockefeller during the 1957 influenza epidemic, and the study of influenza, together with measles and other myxo- and paramyxoviruses, became the primary focus of his research. It is often noted that he cultured, from his own throat, a flu strain that became widely used in the laboratories of other scientists. His research centered upon the mechanisms by which these viruses multiply, how they invade cells, and how they replicate. Purnell’s pioneering studies of respiratory viruses, together with key discoveries of other virologists, facilitated vaccine development and antiviral therapies for these agents, including the rapid development of COVID-19 vaccines targeting the coronavirus spike protein. As a mentor, Purnell was highly appreciated as a kind and generous advisor. A former associate has observed that he was encouraged by Purnell to think creatively and to be independent. With his funds, Purnell paid for the experiments, thus freeing this junior colleague to follow his own instincts. Purnell was appointed Professor and Senior Physician at Rockefeller in 1970. Later he assumed the positions of Leon Hess Professor of Virology, Vice President for Academic Programs, and Dean of the Graduate School. Thus, Purnell began to perfect his administrative skills. Throughout his many fruitful years of laboratory investigation, Purnell held a research grant from the Institute of Allergy and Infectious Diseases at the NIH. This long-running grant was scheduled to be submitted for renewal in 1985, but Purnell surprised me, and some others of his colleagues, with the news that he would not be submitting the application. Donald Fredrickson, the new president of the Howard Hughes Medical Institute (HHMI) had invited Purnell to join the organization as Vice President and Chief Scientific Officer, and Purnell embraced the challenging, but intriguing, opportunity to participate in engineering a rebirth of HHMI. An injection of considerable new funds into the endowment of HHMI had recently been effected through the decision of a newly appointed board of prescient trustees to sell Hughes Aircraft Company to General Motors for $5.2 billion. The company was solely owned by HHMI and had constituted its entire endowment. This large infusion of ready funds made it possible to realize a rapid expansion of the modest institute that had been founded by Howard Hughes in 1953. The institute moved its headquarters from Coconut Grove, Florida, to Montgomery County in Maryland, bringing it into physical proximity to the campuses of the NIH, the Uniformed Services University of the of the Health Sciences with the National Naval Medical Center, and of Walter Reed National Medical Center. Shortly after he assumed his new position at HHMI, I received a call from Purnell asking me to join him as part of the team that would structure the institute to emerge from relative obscurity into national prominence in the support of biomedical science. It was an irresistible opportunity for me, and I joined as Purnell’s first hire. HHMI is a medical research organization (MRO), not a foundation, and has unique requirements as to how it must expend its funds as an MRO. HHMI was required by Internal Revenue Service regulations at that time to spend each year at least 3.5% of its endowment on the support of the investigators who, as employees, conduct HHMI research at the institutions in the United States where they continue to hold academic appointments. Beyond that required expenditure, HHMI can use its funds in support of biomedical research and education through such mechanisms as grants, fellowships, and scholarships to individuals or institutions. Although the researchers it supports as HHMI investigators are employees of the institute, they were required, at hire, to have and retain solid faculty positions at their institutions and to have no administrative duties during their tenure with HHMI, in order to focus directly on their own programs. This prohibition on administrative duties was lifted after Purnell’s presidency, when it was realized that it was contrary to the institute’s mission to build excellence in biomedical research by not allowing HHMI investigators to serve as department chairs, where they could build stronger research entities. Thus, HHMI selects promising and creative scientists and supports their careers, not specific research proposals. They can test their creative ideas with institute funds without needing the data and preliminary results that would be required for successful submission of a grant application to, for example, the NIH. This freedom has permitted the initiation of many creative and successful ventures. When Purnell arrived at HHMI, there were 96 investigators at about 22 institutions, and the annual budget was $77 million. At the time he announced his plans for retirement, he presided over an organization with 330 investigators, located at 72 universities, academic medical centers, and other research institutions in the United States, a remarkable increase. The overall annual budget had grown to $556 million. Included in this budget were also awards of more than $90 million through the grants and special programs office, primarily for support of education in United States at every level, from elementary school through high school, college, graduate school, and postdoctoral studies, as well as research grants to creative scientists in selected foreign countries and engaged in fundamental research. One of the first tasks that Purnell undertook was to formalize and strengthen the selection process for new investigators, as well as to establish a rigorous process for assessing the research of current investigators and criteria for their reappointment. Purnell favored a two-tier review system, with the Medical Advisory Board (MAB) having overall review and advisory responsibilities and composed of representatives of each of the institute’s program areas, and a specialized Scientific Review Board (SRB) for each of the areas of special interest. Leading scientists in these areas gladly accepted his invitations to serve on these advisory and reviewing boards. Initially the institute had supported scientists working in cell biology, genetics, immunology, and neuroscience. A fifth area, structural biology, was added at this time, and prospective new investigators in this area were identified and appointed. Structural biology was just emerging as a force in biologic and medical research, and subsequent contributions of this cohort quickly demonstrated its fundamental importance to progress in the biomedical sciences. As Purnell’s tenure as president neared its end, computational biology was added to the areas of emphasis. Potential investigators were nominated by their institutions; their credentials and prospects were reviewed by the relevant SRB and by the MAB. For the successful candidates, negotiations were carried out between HHMI and their institutions regarding salary, research space, funding, and the like. The institute, under Purnell’s administration, was committed to supporting the women who were employed by the institute at salaries on par with male investigators at the same academic level and discipline. I remember attending one rather tense conversation with an administrator at an institution regarding the salary of a female scientist whose current remuneration was far below that of her peers. It was eventually agreed that her salary would be raised immediately upon hire to the higher level, and not incrementally over the years of her appointment, as had been requested. As the institute’s endowment grew through wise investments and prudent expenditures, it was possible for the number of investigators supported to be quite rapidly expanded. Under Purnell’s guidance, national competitions were announced. Institutions in the United States were invited to nominate a limited number of faculty members for consideration as HHMI investigators. The promise, plans, and accomplishments of these nominees were rigorously considered by the institute’s review panels and advisory board. Selections were made, and agreements were established with their institutions. This outreach to include new institutions was enthusiastically received and diversified the roster of investigators. From his earliest days at HHMI, Purnell aimed to make the scope and quality of research conducted in the institute’s laboratories broadly known and appreciated. HHMI published a formal annual scientific report on the research of each of its investigators, but he envisioned a volume that provided an informal, concise, but informative and interesting, picture of the current and projected research. He anticipated that the investigators would each prepare a personal statement of interest to their peers at HHMI, the trustees and management, the scientific and review boards, and others in the greater scientific and academic community and in government. Thus, an annual “Research in Progress” was born and well received. The publication was not merely a typical compilation of work, but a vivid portrayal of these amazing people and their accomplishments. HHMI investigators conduct biomedical research at the cutting edge of their fields, and their funding constitutes the largest fraction of the institute’s budget. The major goal the HHMI Grants and Special Programs Office is to provide support to ensure that there are succeeding generations of well-trained scientists to carry this cutting-edge research into the future. An additional and important objective is to increase the level of science literacy in the general population. The largest single program here was for the support of college undergraduate science education, including grants for precollege outreach programs. By the end of Purnell’s presidency, HHMI, through this mode of funding, had provided grants for major resource needs to such institutions as medical schools and museums, aquaria, botanical gardens, and zoos, all in support of biomedical research relevant to HHMI programs. Funds were provided for science courses at Cold Spring Harbor Laboratory (Cold Spring Harbor, NY, USA) and the Marine Biological Laboratory (Woods Hole, MA, USA). The Jackson Laboratory (Bar Harbor, ME, USA), also received funds for support of its treasured mouse collections. Research grants were made to innovative researchers in selected foreign countries. The first such awards were made to scientists in Mexico and Canada, and the program was later considerably expanded to other countries. Inspired by a similar annual event at Rockefeller University and in outreach to the institute’s neighbors in the Washington, DC area, Purnell instituted annual HHMI Holiday Lectures on Science for local high school students. In the first year, 200 excited students selected by their schools met at the institute’s new conference center in Chevy Chase, Maryland for the first lectures. Several years later, HHMI began broadcasting the lectures by satellite to schools around the country, where they were enthusiastically received. The first speaker that Purnell selected for these broadcasts was Thomas Cech, an HHMI investigator and Nobel Prize winner who later succeeded Purnell as the president of HHMI. “The Double Life of RNA” was the title of his four lectures. An early partnership was established with the NIH whereby students could obtain research experience through working with scientists in the NIH laboratories in Bethesda. The administrative offices for the program were located in a former cloister on the NIH campus, and the fellows were referred to as the Cloister Scholars. The program continued through Purnell’s tenure. In 1993, HHMI moved to its current headquarters and conference center on a serene property in Chevy Chase. Purnell was deeply involved in its planning and construction, even specifying the species of tree to be planted at the entrance to the residential conference center. Many productive exchanges of ideas and collaborations occurred among scientists who might otherwise not have met. Upon his retirement from HHMI in 1999, Purnell joined the prestigious Washington Advisory Group. The organization had recently been founded by experienced leaders in scientific and engineering research and in higher education to provide advice on research strategy, management, and leadership to governments, universities, research foundations, and companies. Once again, my phone rang, and Purnell asked if I would assist the group with some of their new clients, especially in the areas of medical and biomedical research and training. Purnell was deeply engaged, and for me, it was a pleasure and an education in a different type of science administration to observe Purnell’s considerable prowess here. Purnell had an active interest in many areas apart from virology and biomedical science. He was fascinated with the history of Howard Hughes and the company upon which Hughes' considerable fortune was based. Perhaps this was inspired by the 9-year-old Purnell's seeing Hughes in person at an airfield in Baton Rouge, where the industrialist and aviator had stopped to refuel his plane. Purnell researched the invention and development of the di- and tri-cone rotary drill bits that dramatically improved the drilling process at oil drilling rigs and established the considerable wealth of the Hughes Tool Company. Purnell was reported to be a skilled dry fly fisherman and enjoyed relaxing at the family property in Pennsylvania. He and Joan (his wife of 62 years) were active theater and concert attendees and supporters. It is not surprising that their daughter Kathleen chose a career path in the sphere of arts and entertainment. Purnell noted proudly that in a Google search, he found more citations for his daughter than for himself. Purnell died on July 3, 2021. He had served as a member of the Albert and Mary Lasker Foundation’s Board of Directors after leaving HHMI. He had been a member of the National Academy of Sciences, since 1977, and a member of the National Academy of Medicine. He was a fellow of the American Philosophical Society and the American Academy of Arts and Sciences. Among his honors were the Howard Taylor Ricketts Award of Science of the University of Chicago and the Selman A. Waksman Award of the American Society of Microbiology. During the early 1980s, he was a member of the group that founded the American Society for Virology, and he served as its president during 1985–1986. Purnell Choppin was a wise, dedicated, and kind man, who made important contributions to biomedical science and practice through his own laboratory investigations, his mentorship, and his considerable skills and insights as an administrator. He will be missed by all who knew him, especially so by those who worked with him. He certainly provided me with unique, once-in-a-lifetime experiences. I am grateful. The author declares no conflicts of interest.