Paths to the discovery of antivenom serotherapy in France

Abstract

The current study presents a descriptive chronological survey of the articles published by Césaire Auguste Phisalix and Albert Calmette on snake poison, with the aim of shedding a light on the areas of research and reasoning followed by these scientists, leading up to their simultaneous discovery of antivenom serotherapy in 1894. The path taken by Phisalix is revealed in 15 articles that demonstrate the motivation of a naturalist and the way he confronted the puzzle of immunity against snake venom. In the case of Calmette, two articles preceded the discovery; microbiology was his theoretical base and the Pasteurian spirit of solving health problems his driving force. These two researchers followed distinct paths, mobilized by different motivations, but produced one single result. It is incontestable that the discovery of antivenom serotherapy was the work of two groups of researchers who deserve equal recognition, but who, in fact, did not receive it. Following the discovery both Calmette and Phisalix returned to their previous motivations. Calmette put the discovery into practice and began to produce antivenom serum in Lille. He came to be generally considered as the sole discoverer of antivenom serotherapy and was the recipient of a number of prestigious prizes. Phisalix, on the other hand, received little recognition and returned to his original interests, devoting himself to research on natural immunity. In Brazil, the discovery of antivenom serum therapy had a profound impact on the work of Vital Brazil Mineiro da Campanha, a researcher known worldwide for his scientific discoveries and for the evidence of the specificity of antivenom serums.

Alpha-type phospholipase A2 inhibitors from snake blood

“…Interestingly, the production of specific antivenom was started by Vital Brazil in the 1900’s and it was Vital Brazil who also discovered the effectiveness of the polyvalent antivenom [87, 88]. At that time, antivenom was prepared with crude plasma of hyperimmunized animals.…”

“…Nowadays, despite advances in the production of antivenoms, this production is still similar to the methods originally described by Vital Brazil [87, 88]. Currently, immunoglobulins or immunoglobulin fragments [F(ab’)2 or Fab] purified from serum are used in antivenom [2].…”

B Lymphocyte as a Target of Bacterial Infections

“…Von Bering and Kitasato in 1880 present their first work on serotherapy, showing that in the serum of animals immunized with diphtheria or tetanus toxins, there were specific elements of recognition for these toxins and that their use in patients conferred protection [2]. Later, Phlizalix and Calmette groups independently produce antisera against snake venoms [3], confirming the relevance of specific serum elements for the protective response. In those days, histological studies on organs of experimental animals subjected to immunization processes suggested that lymphoid organs were sites likely responsible for the synthesis of the serum elements responsible for protection against toxins and poisons [4].…”

Preparation and neutralization efficacy of IgY antibodies raised against Deinagkistrodon acutus venom

“…The conventional antivenom is generally produced from the blood of the large animals, frequently horses or sheep, immunized with the venom of a single snake or mixed venoms obtained from several animals to eliminate the intraspecific diversification [7]. Nevertheless, the serum used to treat snakebite victims may cause various side effects, such as anaphylactic shock, pyrogen reaction and serum sickness, which are mainly caused by the nonspecific proteins found in commercially available antivenoms [8–11].…”