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Commentary on ‘Fifty years with Aspirin and Platelets’

The Gaddum International Lecture, and its precursor the Gaddum Memorial Lectures, commemorate and celebrate the contributions made by John Henry Gaddum (FRS) to the discipline of Pharmacology. One of Gaddum's major contributions was to define the characteristic features of a Pharmacologist—‘The Pharmacologist has been a jack of all trades, borrowing from physiology, biochemistry, pathology, microbiology and statistics—but he has developed one technique of his own and that is the technique of bioassay’ (Gaddum, 1964). Such ‘borrowing’ of techniques from other disciplines is nowadays recognized and highly regarded as a ‘multi-disciplinary approach’ to research. A clear example of this approach was presented at the very beginning of Patrono's ‘personal testimony’ of his ‘Fifty years with Aspirin and Platelets’, with his search for an antibody against PGF2α, to be used in the then recently developed technique of radioimmunoassay. Later, the identification of the highly potent, but ephemeral, platelet aggregating eicosanoids (PGG2, PGH2 and TxA2) was achieved by two groups, one led by ‘John Robert Vane, a chemist turned pharmacologist’ and the other by ‘Bengt Ingemar Samuelsson, a medical doctor turned chemist’. Such ‘borrowing’ and multi-disciplinary approaches have continued in Pharmacology, taking full advantage of the unprecedented advances in chemistry, biochemistry, physics, molecular biology and genetics, made in the five decades since 1971. Most of these advances have generated new techniques and methods that have been borrowed to analyse the interactions between aspirin, the eicosanoids and the blood platelet (thrombocyte) and then to develop, from such analysis, a clinically viable and highly effective medical procedure (low-dose aspirin) which has undoubtedly saved many lives. Borrowing techniques from other disciplines is still a vital characteristic, crucial to the progress of today's Pharmacology. The technique particular to Gaddum's Pharmacologist – the bioassay – was represented in the Lecture by the critical breakthrough in the study of platelets, with platelet aggregometry. This assay method allowed platelet function to be studied easily, reliably and in greater scientific detail. Crucially, this bioassay, from the beginning, was applied to human platelets, thus immediately increasing the relevance of the data gathered. Although there are, now, other more modern assays of platelet function (Flower, 2018)—using whole blood instead of platelet-rich plasma, and using impedance or flow cytometry instead of light photometry—they still measure the aggregation of platelets as the standard test of platelet function. This bioassay has been crucial to the exploration of platelet pharmacology for over 60 years and is still providing new scientific data, along with valuable clinical results.