Samuel H. Speck, PLOS Pathogens Section Editor, and Alexander Poltorak, Associate Professor at Tufts University, remember their friend and colleague David Thorley-Lawson, and reflect on his contributions to the understanding of Epstein-Barr virus.
Epstein-Barr virus (EBV), a gamma-herpesvirus and the first human tumor virus identified, was discovered in 1963 from studies of Burkitt’s lymphoma samples obtained from children with the disease in what is referred as the malaria belt in Central Africa. Since that time there has been intense interest in how this ubiquitous human virus – which chronically infects the vast majority of the human population – leads in a small percentage of infected individuals to cancer. The list of cancers in which EBV infection plays a role has grown to include near all cases of nasopharyngeal carcinoma, 30-40% of Hodgkin’s lymphoma, 10% of gastric carcinoma, and about half of the lymphomas that arise in immunosuppressed transplant and AIDS patients. On June 25th the EBV field lost one of the major contributors to understanding the complex relationship between EBV and its human host, Dr. David Thorley-Lawson, who died at the age of 68.
David earned his bachelor’s degree in Biology from the University of East Anglia. He then studied Biochemistry at the National Institute for Medical Research in England, where he completed his doctorate under Dr. Michael Green. There he met his future wife, the renowned immunologist Dr. Brigitte Huber – a Professor at Tufts University, who at that the time was completing her doctorate in Immunogenetics at the University of London. They married and moved together to Massachusetts, where David continued his training as a postdoctoral researcher at the Dana Farber Cancer Institute.
David spent his 35-year career at Tufts University School of Medicine investigating EBV – pursuing the difficult questions surrounding EBV pathogenesis in humans. Early studies done by others had shown that EBV could growth transform human B lymphocytes in tissue culture – which seemed to explain why it could “cause” the cancers it was associated with. However, as is often the case in science, further studies revealed that the pathogenesis of EBV was far more complicated. Most notably, it was determined that EBV gene expression in EBV-associated tumors was distinctly different than that observed in EBV transformed B cell lines in culture – leaving in doubt the role of EBV growth transformation in genesis of these tumors. David’s lab carefully dissected EBV infection of B cells in infected humans, providing seminal contributions to our current understanding EBV pathogenesis. Arguably his most important work was characterizing, at the level of single infected cells, precisely what EBV genes are expressed in specific populations of infected B lymphocytes. This was extremely arduous work, given the available techniques at the time, and was meticulously carried out. These analyses showed that EBV infection of naïve B cells in vivo leads to expression of the growth transforming EBV latency program, apparently driving these cells into germinal centers – where a more restricted program of EBV gene expression is observed. Ultimately, he showed that EBV circulates in the periphery in memory B cells where little or no viral gene expression is observed. Based on this information, he was then able to correlate these results back to the patterns of EBV gene expression observed in different B lymphomas to provide evidence for their origin. Furthermore, he extended these analyses to develop an elegant mathematical model for EBV persistence in the infected host.
David had both a keen intellect and a willingness to tackle difficult scientific problems. He was very invested in mentoring students, training more 30 of them. He never imposed his thinking on students, but rather challenged them with outstanding questions and encouraged them to think in order to resolve the problems they were facing. Not surprisingly, his trainees developed the ability to think independently. David frequently challenged dogma and thought outside of the box. Recently, raising standards for graduation was his latest concern expressed at faculty meetings. He was the Qualifying Exam Moderator for many years, and was able to bring the best out of the students. He was very involved in establishing the Immunology Graduate Program at Tufts – playing a major role in laying out the fundamentals of the program. To his colleagues and friends, David was very engaging and willing to tirelessly debate both new ideas and the interpretation of previous studies. He was most appreciated for his intellectual honesty and genuine curiosity for how things work – traits that served him well in his research.
Samuel H. Speck is a Section Editor at PLOS Pathogens, a Georgia Research Alliance Eminent Scholar, and a Professor of Microbiology & Immunology at the Emory Vaccine Center at Emory University School of Medicine.