Oxford Medicine THE NEWSLETTER OF THE OXFORD MEDICAL ALUMNI OXFORD MEDICINE • DECEMBER 2020 Professor COVID Vaccines Frontline Osler Rowing Ledingham Perspectives Revival 91 Not Out! And much more... Pictured: Professor John Ledingham 2 / OXFORD MEDICINE DECEMBER 2020 President’s Piece Vaccines for COVID-19 3 So much is at stake. We stand at an extraordinary Prof Charles Bangham inflection point. But where to start? Professor John GG Ledingham - 7 ‘I would adopt an A to E approach’ is the phrase 91 Not Out! currently used by young doctors when faced with a catastrophic problem, or when they have The Spirit of Brexit: Past, Present and 10 no idea what to do. I tried it with this edition: Future - Prof Alastair Buchan A - Anatomy and Augmented Reality; B -Brexit; Augmented Reality for Anatomy C - COVID…then I thought about an approach I 12 Dr Matthew Williams and Mr Tom Cosker Dr Lyn Williamson used as a young house physician - ‘What would OMA President J Led do?’ Frontline Perspectives - Prof Chris 14 Professor John Ledingham is one of Oxford’s Conlon (Oxford Update), Prof Neil Mortenen great clinicians and teachers. He has inspired generations of doctors, (Surgery), Dr Sarah Lowndes (Oncology), Dr including many who have contributed to this edition. He shares Will Seligman (ICU Reg), Dr Hannah Thould memories of his career in an interview which is warm and honest, (SHO), Dr Bernard Bukala (F1) spiced with pithy anecdotes and words of wisdom. This interview Alumni Letters 21 introduces ‘Recollecting Oxford Medicine,’ a 10-year project by Dr 'Memories from the Wittery' (Dr Carole Derek Hockaday and Dr Peggy Frith to preserve an oral history of Robertson) Oxford medicine through interviews, archived as podcasts in the Bodleian library. 'An Old Duffers Tale' (Dr Tim Crossley) 'Tingewick Remembered' (Prof Sir Terence We pay tribute to another great Oxford clinician - Professor Peter Stephenson) Sleight who died earlier this year. Through extracts from his ROM interview, he shares his story in his own words. 'Finding Your Own Voice' (Dr Mary Ryan) Dr Adam Our frontline clinicians have learned to adapt to the constancy of Tales from the Land of Oz - 24 change. Their voices are important. We hear from different specialities Skinner and Dr Luke Williamson and different generations of doctors. Recollecting Oxford Medicine 26 Professor Charles Bangham tackles the issue at the forefront of our Dr Derek Hockaday and Dr Peggy Frith minds – a vaccine for COVID. His elegant summary of immunology and vaccinology is a must-read for those of us who need help making The Oxford Textbook of Medicine, 27 sense of the many vaccines just around the corner. Sixth Edition - Dr John Firth Augmented Reality for anatomy teaching? Mr Tom Cosker and Matt Osler House Rowing Club Revival 28 Williams whet our appetites for this new teaching aid for surgeons and Jennifer Holmes, Prof Simon Smail CBE, medical students. Dr Patrick Carroll, Dr Graeme Rocker, Dr Lesley Starr, Dr Sally Hope, Dr Tim Crossley, Osler House in Berlin is something to look forward to in Europe post- Dr Lyn Williamson Brexit and we are grateful to Professor Alastair Buchan for his update. Dr Catherine Swales (DME) describes her mission to maintain Congratulations 33 excellent teaching at the medical school. The Osler Medical student reports are full of infectious energy, not least from the Osler House Obituaries Rowing Club revival. 34 There is much to be thankful for. Oxford scientists and researchers have News from the Medical School 38 led the world in their response to the pandemic. The world looks forward Dr Catherine Swales their results. We congratulate Dr Keith Hawton on his CBE for work on suicide prevention, Dr Sarah Walker on her OBE for services to Academia Osler House News - Thomas Brockwell 40 and the CV response, Dr Ravi Gupta listed Times Top 100 for his work on HIV. There is a new edition of the Oxford Textbook of Medicine. Tingewick News - Madeleine Oliver 41 We feature contributions from forty alumni spanning EIGHT decades and by ‘clicking on the links’ you will be able to hear voices of OMA Christmas Quiz & Crossword - Dr Neil 42 members, past present and future. Thank you all. Snowise and Mr David Williamson As the nights draw in and the second wave does its worst, I prescribe Optimistic Poem - Dr Lesley Starr combination therapy: 44 • A heavy dose of nostalgia provided by early Osler House rowers OMA Update 45 and other Alumni letters Quiz and Crossword Answers • A cocktail of clever, witty and thought-provoking pieces provided 46 my family and friends from the 79-81 graduates. Cartoons - Dr Chris Mason In my 64th year, ‘I got by with a little help from my friends’. 47 To use the 2020 sign-off: Stay well and take care everyone. Back Cover Photos - Dr Chris Roberts 48 Dr Lyn Williamson Design by - Lucy Jonas (portfolio) 46 OXFORD MEDICINE DECEMBER 2020 / 3 Vaccines for COVID-19: a primer Professor Charles Bangham, Whereas the innate immune response is not specific to Professor of Immunology; Head, one virus, the acquired immune response consists of Division of Infectious Diseases, antibodies and T cells that are specific to the antigens Imperial College London. Lincoln in that virus. On first exposure to a new antigen, the College 1977-80 frequency of antibody-producing B cells and T cells specific to that antigen is very low (around one in a Charles qualified in medical million), and it takes around a week for the growth of sciences at Cambridge sufficient numbers of B and T cells specific to the new and clinical medicine at Oxford. In 1995, antigen to mount an effective immune response. This he was appointed Chair of Immunology, first week of a viral infection is of particular importance and since 2013, Head of the Division of in infection with SARS-CoV-2, the causative agent of Infectious Diseases, Imperial College Faculty COVID-19. of Medicine. Since 1987, he has conducted research on the immunology and virology Antibodies are of critical importance in an efficient antiviral response. However, even in a secondary of persistent viral infections, especially the infection, antibodies alone are rarely sufficient to human retrovirus HTLV-1. Charles is a Wellcome completely prevent an infection. There is a frequent Trust Investigator and a Fellow of the UK misconception concerning the importance of Academy of Medical Sciences. He has chaired neutralizing antibodies. Neutralizing antibodies are many national and international grant review those that inactivate a virus in a short-term assay in panels. He was awarded the BMC Retrovirology vitro. But the standard in vitro neutralization assays Prize 2007, the International Retrovirology fail to measure two major mechanisms by which Association Basic Science Prize 2015, and the an antibody can kill the virus in vivo: complement- David Derse Memorial Award from the National dependent lysis and antibody-dependent, cell-mediated Cancer Institute, USA, in 2018. He is a Visiting cytotoxicity (ADCC). Therefore, the protective value Professor, Kyoto University, Japan. In 2019, he of antibodies in vivo may correlate better with the was elected a Fellow of the Royal Society. total titre of virus-specific antibody (including the neutralizing antibody) than with the titre of neutralizing What can we expect of an anti-viral antibody alone. vaccine? Many of the most effective antiviral vaccines are An effective anti-viral vaccine will prevent or diminish modified, attenuated viruses, derived either from the symptoms, severe disease, and onward transmission pathogenic virus itself or from a vector such as an of the virus. Vaccines rarely - if ever - completely adenovirus that expresses one of the genes of the block reinfection of an individual with the same virus, pathogen. The reason that attenuated viruses are as is shown by the production of a secondary immune particularly efficient vaccines is because they elicit, in response. The term “sterilizing immunity” is therefore addition to antibodies, both helper (CD4+) T cells and probably a misnomer. cytotoxic (CD8+) T cells. The helper T cells are essential both to help the antibody response and the cytotoxic T The immune response to viruses cell response, and to elicit a high frequency of memory lymphocytes - both B cells and T cells - which can The innate immune response is triggered within hours respond more rapidly to a reinfection with the same of infection. The most important component is the virus. It is the cytotoxic T lymphocytes that are usually interferon response: almost all nucleated cells in the essential to eradicate a virus from the body, by killing body are capable of producing type 1 (alpha or beta) virus-infected cells. interferons, which in turn activate the expression of a large number (c.300) of genes that combat the virus by How long does immune protection last? several parallel molecular pathways. The complement system, cytokines and chemokines also contribute to The duration of protection differs widely between the innate immune response. Finally, natural killer (NK) antiviral vaccines. Some, such as those against Yellow cells and dendritic cells (DCs) are the two main cellular Fever and Measles viruses, provide excellent protection components of innate immunity. for many years, even life-long. By contrast, the protection given by the influenza vaccine typically lasts The innate immune response has two chief functions. much shorter because the immune response that it First, it directly inhibits the growth and spread of the elicits wanes relatively quickly and the influenza viruses virus, via interferons, complement and NK cells. Second, continually evolve. it mobilizes and stimulates the acquired immune response, via DCs, complement, cytokines and chemokines. 4 / OXFORD MEDICINE DECEMBER 2020 Apart from the highly pathogenic coronaviruses SARS, MERS and SARS-CoV-2 that have recently emerged in the human population, four endemic coronaviruses have circulated widely for many years.