Laureation address: Sir John Skehel
Laureation by Professor Rick Randall
School of Biology
Chancellor, I have the honour to present for the degree of Doctor of Science, honoris causa, Sir John Skehel, Fellow of the Royal Society.
Viruses cause a wide range of serious human, animal and plant diseases, such as HIV, EBOLA, herpes, smallpox, measles and influenza. Influenza viruses cause seasonal ‘flu and occasionally, but regularly, worldwide pandemics such as the 1918 pandemic which killed more people than the Great War. Sir John has worked on influenza viruses for most of his career at the National Institute for Medical Research (NIMR) where the influenza virus was discovered in 1933. Unlike bacteria, which can be free living, viruses must replicate inside living cells and to do this they have to transfer their genetic information from one cell to another inside specialised particles we call virions. Once inside a cell the virus’s genetic information redirects the cell’s machinery to make more virions that are released from the infected cell and can infect neighbouring uninfected cells or be shed into the environment to infect susceptible individuals. However, viruses do not just bump into cells and somehow magically transfer their genetic information into the cell. Rather, viruses have on their surface projections that specifically bind them to their target cell. You might visualise viruses as balloons containing genetic information with different shaped Velcro on their surfaces that binds them in different ways to their target cells. However, once bound to a cell the viruses’ problems are not over. They somehow have to get their genetic information from inside the balloon into the cell.
Using structural techniques Sir John’s research has shown the molecular events of how influenza viruses enter cells. Together with Don Wiley and others, he first resolved the structure of the projection (Velcro), or haemaglutinin molecule or HA as we call it, on virions that binds influenza viruses to cells and then subsequently showed how the HA molecule undergoes a massive conformational change to trigger a fusion event that results in the release of the virus’s genetic information into the cell to initiate the infectious process. This work was the first time the binding and entry process of any virus was understood at the molecular level. Furthermore, by understanding the structure of the HA protein it became clear how our immune response, in producing antibodies that bind to influenza viruses, prevents influenza viruses from infecting cells. By comparing the HA structures of different strains of influenza viruses the work also showed why antibodies against one strain of influenza virus do not block the infectivity of another strain. Excitingly, a full appreciation of how antibodies inactivate, or neutralise, influenza viruses holds out the promise of one day being able to make a universal vaccine against all human influenza viruses. Sir John’s comparative studies on the HA structure of human and avian influenza viruses have also revealed why not all avian strains of influenza viruses are likely to infect humans and how they might have to adapt to do so. For many years Sir John was also Director of the World Health Organisation (WHO) influenza virus centre at the NIMR, which is a world reference centre that monitors the strains of influenza viruses circulating in the human population and thus plays a central role in helping to decide the composite of the annual influenza virus vaccines.
For his pioneering work on how influenza viruses bind to and enter cells, Sir John has received many awards and accolades, including the Wilhelm Feldberg Prize and the Royal Society’s Royal Medal. As well as his pioneering research Sir John was Director of the National Institute of Medical Research from 1987 to 2006, overseeing many of its scientific successes and the beginnings of its metamorphism into the Francis Crick Institute. So-called retirement does not appear to have slowed him down. He still runs a very active and successful research group at the NIMR, is on many scientific advisory boards, including the Pasteur Institute in Paris, and is Biological Secretary and Vice-President of the Royal Society.
Sir John’s connections with St Andrews go back a long way. In 1985 a group of virologists, including myself, under the direction of Professor Willie Russell moved from the NIMR to St Andrews to set up a virology group here. After some initial scepticism, Sir John has been nothing but supportive and encouraging of the virology group here, coming on numerous occasions to give lectures about his work and to advise us strategically, for which we sincerely thank him.
Chancellor, in recognition of his truly pioneering work on the molecular mechanisms of influenza virus entry into cells, I invite you to confer on Sir John Skehel the degree of Doctor of Science, honoris causa.