CONFLICTS-OF-INTEREST - THE GENESIS OF SYNTHETIC ANTIMALARIAL AGENTS IN PEACE AND WAR

Malaria has had an enormous impact on human history, not least in time s of war. The disease has been treatable by a natural remedy, quinine, since the 17th century, but the production of synthetic antimalarial agents was first achieved in Germany in the wake of the Great War of 1 914-1918, in which malaria had caused immense problems. In the 1920s r esearch workers in the Bayer laboratories of the IG Farbenindustrie co nsortium developed the 8-aminoquinoline plasmoquine (the forerunner of primaquine). They went on to develop the acridine dye, atebrin (mepac rine) and the 4-aminoquinolines, Resochin (developed at the end of the Second World War in America as chloroquine) and Sontochin. British at tempts to match the advances achieved by the Germans were at first unp roductive, partly because collaboration between academic and industria l organizations in the UK was beset by concerns over patent rights. Ho wever, with the outbreak of World War II, when supplies of antimalaria ls were scarce, ICI succeeded in the large-scale production of mepacri ne (essential to prosecution of the war, particularly in the Far East) and also initiated a programme of collaborative research that eventua lly led to the discovery of proguanil (Paludrine); this, in its turn l ed to the diaminopyrimidine, pyrimethamine. A massive cooperative scre ening programme in the USA during World War II eventually bore fruit i n the realization of the therapeutic potential of chloroquine, and in the later development of amodiaquine and primaquine. Some of this work also influenced the subsequent discovery of mefloquine and halofantri ne at the Waiter Reed Army Institute of Research.