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.

Keywords: :

• Snake venom
• Hemostasis
• Platelet function
• Coagulation.

Notes

¹Martin's work was recognized by him being elected as Fellow of the Royal Society in 1901, but even this accolade did not enable him to secure a tenured position at the University of Melbourne. Ironically, his path to tenure was blocked by the life-long professorial appointment of George Halford, who had worked on Australian snake venoms at Melbourne before Martin (University of Melbourne, 1914). Martin returned to Britain in 1903 where he became the inaugural Director of the Lister Institute for Preventative Medicine. Upon retirement in 1930, Martin returned to the CSIR Division of Animal Nutrition at University of Adelaide and was further honored by the creation of C. J. Martin traveling scholarships by the National Health and Medical Research Council of Australia (Hawgood, 1997).

²History will, of course, remember Gwyn Macfarlane for his cascade theory of blood coagulation. Cecil Hougie believed that the most cited and the two most important papers on blood coagulation of the 20th century were the independent reports of the cascade phenomenon by Macfarlane in Nature (1964) and of the waterfall effect by Earl Davie and Oscar Ratnoff in Science (1964) (Hougie, 2004). However, 40 years ago, the blood coagulation theoreticians were engaged in the most intense foment of disagreement. Walter Seegers, a biochemist in the United States regarded Macfarlane's cascade theory to be at the “speculative level of science created with the wild use of the imagination” (Seegers, 1965, p. 220). Despite this invective, the Macfarlane–Davie–Ratnoff cascade mechanism has stood the test of time.

³Knoll Pharmaceuticals in Lugwigshafen, Germany, continued to manufacture Ancrod (Viprinex) from a collection of several hundred vipers. The drug has not gained FDA approval in the United States.