Sir James Gowans, CBE FRS FMedSci, died peacefully at home in Oxford on 1 April 2020 at the age of 95. He was a towering figure, literally in his height as well as in his science, from the period of the great blooming of British immunology in the 1950s and ’60s when the BSI was founded. Our Society offers its sympathy to his widow, Moyra, to his children and to all his family.
The idea of clonal selection as the cellular basis for acquired immunity developed during the 1950s. Preliminary formulations by Talmage and Jerne culminated in Burnet’s famous monograph in 1959. It raised two overarching questions. First, how could mono-specific, very infrequent clones be certain to promptly encounter their cognate antigen, wherever it might enter the body? Second, how could diversity be generated, even before antigen had arrived?
The recirculation of lymphocytes from blood to lymph to blood, round and round the body through all secondary lymphoid organs in perpetual procession, compellingly answered the first question.i It was the physiological experiments by Sir James (Jim) Gowans that established this, published from 1957 onwards while he was a postdoc and subsequently as Director of the MRC Cellular Immunology Unit. He took the millions of pure lymphocytes that drain hourly from a cannula placed in the thoracic duct of a rat, then followed their fate when returned intravenously to that rat. Most re-emerge from the cannula within a couple of days, having left the blood via high endothelial venules within lymphoid organs into efferent lymph. When an antigen is administered, it or its fragments lodge in a nearby rendezvous, such as a draining lymph node or the spleen. Then, within less than a day, it engages and extracts the rare, matching lymphocytes from the recirculating population.
Gowans and his co-workers showed that the three main states of readiness of the specific adaptive immune system are wholly due to the properties of the body’s small, nondividing lymphocytes: (1) unimmunised, naïvely awaiting antigen to trigger a primary response; (2) primed, by prior exposure to antigen to inculcate memory; or (3) specifically tolerised, for example by neonatal exposure to transplantation antigens. Recirculating lymphocytes ‘underwrite’ (his favourite word) the body’s adaptive immune readiness.
He also noticed that, among the minor population of large lymphocytes in the thoracic duct, some migrate in a once through, non-recirculating transit to the lamina propria of the gut wall. These were B lymphoblasts recently stimulated by corresponding antigens in gut-associated lymphoid tissues. With colleagues, he explored the subsequent IgA responses there. The scope of his immunology was therefore very broad: not just the induction of antibody formation but also mucosal immunity, graft rejection and graft-versus-host reactions. We owe to Gowans more than to anyone else the core dogma that lymphocytes fulfil the central cellular role in the induction and development of adaptive immune responses.ii
Gowans was the only son of a lab pathology technician and a mother who was Swedish by birth.iii He grew up in south London and studied medicine at King’s College London. He joined the student volunteer group providing medical relief at the concentration camp at Bergen-Belsen immediately after its liberation in 1945.
On completion of his medical training he studied for a DPhil supervised by Sir Howard Florey at the Dunn School of Pathology in Oxford, researching whether the therapeutic efficacy of a bacteriostatic antibiotic in mice depended on concurrent inflammation. An exchange scholarship to the Pasteur Institute, Paris, in 1952–3 generated an interest in immunology. On return to the Dunn School, Florey put to him the problem of the lymphocyte. “If you can find out where they go, Gowans, you can find out what they do… The lymphocyte problem has blunted the wits of a lot of people in the lab, Gowans, and I don’t see why you should be spared a similar fate.”iv
Gowans later fulsomely acknowledged his debt to Florey: “It was from Florey that I learned that scientific problems are never solved by polemics but by trying to perform simple, decisive experiments”. The other course-setting influence on his scientific career was his friendship with Medawar, joint recipient of the 1960 Nobel prize for the immunology of transplantation tolerance. Gowans himself received for his lymphocyte work a Royal Medal, a Gairdner prize, the Paul-Ehrlich prize and a Wolf prize.
In 1977 he chose to terminate his lab work, becoming the Secretary (Chief Executive) of the MRC, for ten years. This period gave him satisfactions despite turbulence over many issues, including, for example, the unjustified put-down by prime minister Thatcher about the MRC not patenting monoclonals; the emergence of the HIV epidemic; policy on human IVF and embryo research; controversial clinical trials of folate supplementation during pregnancy. From 1988 to 1993 he was the first Secretary-General of the international Human Frontiers Scientific Programme, working from Strasbourg. He served as adviser to numerous charity and commercial bodies, including Celltech.
But above all, he gained his chief intellectual pleasure by developing contacts with, and strongly supporting, promising young scientists. His imprint continues through his many intellectual descendants, the researchers who themselves learned the value of performing “simple, decisive experiments”.
Emeritus Lecturer in Immunology at the Dunn School of Pathology, Oxford University.
The author gratefully acknowledges help from Jonathan Howard to improve this article.
i. The answer to the second had to await the development of molecular biological analysis of V region gene segments.
ii. The overview by Weissman (2010) provides much fuller context and detail: Nature Immunology 11 1073–1075
iii. See his papers deposited at the Bodleian Library: https://bit.ly/3d4qbjA
iv. Max Blythe interview 5 with Gowans, 1998. The series of five interviews begins at https://bit. ly/3guQAcq