VOLUME 1 - ISSUE 3 - ROD FLOWER - FRS
The Royal Society gave BPS members cause for celebration earlier this year when it elected our president, Rod Flower, to a Fellowship. As many of you will know, Rod Flower, FRS, has made outstanding contributions to pharmacology, both through his research on inflammation and through his tireless efforts to support the pharmacological community and promote the interests of our subject. Rod has published over 200 peer-reviewed research papers, with more than a splattering in journals such as Nature and PNAS, and holds several patents. He has trained many PhD students, some of whom are now internationally competitive researchers in their own right, hosted many researchers from overseas in his group and made important contributions to undergraduate teaching. He has also been instrumental in establishing the William Harvey Research Institute as one of the leading Pharmacology centres in the UK and given his time generously to our Society and its various activities.
Rod’s career in pharmacology began more by chance than judgement. As a schoolboy he enjoyed physics and had a passing flirtation with astronomy but showed no real interest in biological science. He left school with little idea of what he wanted to do and began a career in banking. He soon realised that this was a mistake and turned his thoughts to computing. Searching for opportunities, he saw an advertisement for a computer operator at the Royal College of Surgeons and found himself being interviewed by John Vane. That interview changed his life. With remarkable insight, John offered Rod a position not as a computer operator but as a technician in pharmacology. Rod soon found he was intrigued by the job and the subject and, with John’s support, set about obtaining some qualifications in biology before going to the University of Sheffield to read Physiology. Here his intellect and passion for biological science were obvious to all who knew him and he left with a first class honours degree to return to John Vane’s lab to do a PhD. This was an exciting time, as John’s group was unravelling the mechanism of action of aspirin. In line with this, much of Rod’s early work concentrated on the regulation of prostaglandin synthesis in various model systems; he thus contributed to the first tranche of papers that revolutionised our understanding of the mechanism of actions of NSAIDs and formed the platform for the subsequent discoveries of COX-2 and COX-3.
After completing his PhD, Rod moved with the Vane group to the Wellcome Foundation, where he was given a free rein to develop his own ideas. He chose to focus on exploring the way in which glucocorticoids control inflammation. Despite the clinical effectiveness of these steroids as anti-inflammatory drugs, this was a remarkably under-researched area and, although steroid binding sites had been described in several tissues, the mechanism of steroid action was uncharted territory. To address the problem, Rod exploited classical bioassay systems and before long developed the notion that the steroids modify prostaglandin synthesis via a mechanism which involves receptor occupancy and de novo synthesis of a protein second messenger. This protein, initially called macrocortin or lipocortin 1, was shown by Rod’s group to prevent the liberation of arachidonic acid from membrane phospholipids and thus to act by a mechanism distinct from aspirin and the other NSAIDs. These original studies paved the way for many years’ work which have enthralled Rod and many others. The early studies were not easy. Purified macrocortin (or annexin 1 as it is known today) was unstable and difficult to work with; furthermore, the antisera raised initially were not entirely satisfactory. However, once the gene was cloned and recombinant annexin 1 and other tools became available, progress was rapid. Evidence from Rod’s lab, first during his time as Professor of Pharmacology at Bath and later at the WHRI, confirmed that annexin 1 is an important player in the host defence system, contributing to the regulatory actions of glucocorticoids on, for example, neutrophil migration, iNOS expression, cell proliferation and apoptosis, as well as eicosanoid generation.
While no disease has yet been associated with dysregulation of annexin 1 expression, the group’s discovery of auto-antibodies to the protein in several cohorts of patients with autoimmune inflammatory disease (e.g. rheumatoid arthritis and asthma) added further weight to the importance of the protein. Proof of principle came with the generation of an annexin 1 null mouse which shows aberrant inflammatory responses and resistance to some facets of glucocorticoid action. A key challenge now is understanding how annexin 1 works. Rod’s group have already provided important clues by identifying specific binding sites on peripheral blood leukocytes and determining residues within the annexin 1 molecule that are critical for biological action - with privileged insight, I suspect that exciting new information is on the horizon.
In a short article it is impossible to do full justice to Rod’s many contributions. However, it cannot go without saying that, in addition to leading his own group, he has collaborated effectively with many others and thereby made further contributions to our understanding of the biology of the glucocorticoids and annexin 1. In addition, it must be noted that Rod’s contributions to science, and particularly pharmacology, have been recognised by several bodies, including the BPS through the award of the Sandoz (now Novartis) prize and the Gaddum Memorial Medal, and the Wellcome Trust by the award of a prestigious Principal Fellowship. I know that I am not alone in being delighted that Rod has been elected an FRS and, on behalf of the BPS, offer him our warmest congratulations.