A BRIEF HISTORY OF SNAKE VENOMS AFFECTING HEMOSTASIS

Abstract

The earliest reports of snake venoms affecting hemostasis occur in the 17th century and first half of the 18th century with the observations of Nieremberius (1635), van Helmont (1648), Richard Mead (1702), and Geoffrey and Hunauld (1737). However, our detailed knowledge of this field of toxinology stems largely from the work in the second half of the 18th century of Felice Fontana, who is credited with being the first investigator to inject viper venom into dogs. Fontana's work foreshadowed many seminal discoveries that were to be made in the next 200 years, but a fallow period of research followed Fontana until three Britons took up investigations into snake venoms beginning in the late 19th century: Charles Martin, who worked on Australian snake venoms; Gwyn Macfarlane, who studied Russell's viper venom, initially in relation to the treatment of hemophilia; and Alistair Reid, who worked on the Malayan pit viper and was the first to suggest the use of snake venom thrombin-like enzymes in “therapeutic defibrination” as an alternative anticoagulant strategy. From the 1960s onwards, the explosion of research activity generated in part by molecular biology, has provided a vast amount of data in this field. Notably, studies on venom factors affecting platelet function are part of this more recent history, and in the last 20 years, a wide range of C-type lectins and disintegrins have been discovered. Molecular techniques have now enabled the identification of gene structure, the cloning of genes, the production of recombinant protein, and the elucidation of protein function at the molecular level. Overall, a significant number of snake venom toxins affecting hemostasis have been put to use in both the research and routine coagulation laboratory settings and show much promise in a variety of clinical situations.