Historical links between toxinology and immunology.

Research on bacterial toxins is closely linked to the birth of immunology. Our understanding of the interaction of bacterial protein toxins with immune cells has helped to decipher immunopathology, develop preventive and curative treatments for infections, and propose anti-cancer immunotherapies. The link started when Behring and Kitasato demonstrated that serotherapy was effective against 'the strangling angel', namely diphtheria, and its dreadful toxin discovered by Roux and Yersin. The antitoxin treatment helped to save thousands of children. Glenny demonstrated the efficacy of the secondary immune response compared to the primary one. Ramon described anatoxins that allowed the elaboration of effective vaccines and discovered the use of adjuvant to boost the antibody response. Similar approaches were later made for the tetanus toxin. Studying antitoxin antibodies Ehrlich demonstrated, for the first time, the transfer of immunity from mother to newborns. In 1989 Marrack and Kappler coined the concept of 'superantigens' to characterize protein toxins that induce T-lymphocyte proliferation, and cytokine release by both T-lymphocytes and antigen presenting cells. More recently, immunotoxins have been designed to kill cancer cells targeted by either specific antibodies or cytokines. Finally, the action of IgE antibodies against toxins may explain their persistence through evolution despite their side effect in allergy.

[Behring's personal papers--Behring's lives]. / Behrings Nachlässe--Behrings Biographien.

The article wants to show the connection between the enriched personal papers of Emil von Behring (1854-1917) in the Behring archives in Marburg (established in 1927) and the history of the first biography of the scientist, which was published by Heinz Zeiss and Richard Bieling during Nazi era in 1940. One focus is placed on Behring's widow Else von Behring (1876-1936), who was active in arranging Behring's papers in proper order and in searching a biographer of her husband's life. The paper also presents new discoveries from the Behring Works archives in Marburg which show Behring--founder of the serum therapy and first winner of the Nobel Prize for medicine in 1901--as an entrepreneur who was fighting for control and influence in the field of science and of business: maybe another narration of Behring's life.

Sera-therapy, exile and Franco's regime. The survival strategy of the Ravetllat-Pla Institute in postwar Spain.

The aim of this paper is to analyse the scientific and commercial survival strategy of the Ravetllat-Pla Institute after the Spanish Civil War. Founded in 1923 by Ramon Pla (1880-1956) and Joaquim Ravetllat (1872-1923), it produced two sera: 'Hemo-antitoxin' and the 'Ravetllat-Pla serum'. When the Civil War ended and Ramon Pla was forced into exile, management of this laboratory was taken over by his daughter, Núia Pla Monseny (1918- 2011) who had to deal with an extremely difficult economic, political and commercial situation. In this paper, I analyse the means by which the Institute survived. These involved the Institute's ability to construct different political symbols from 'Hemo-antitoxin'. I study how Franco's repression influenced this survival strategy and Ramon Pla's role in exile. I also analyse the part played in this scientific and commercial process by the Institute's scientific and commercial network in Chile.

Poul Agerholm Christensen MD (1912-1991): antivenom production at the South African Institute for Medical Research.

Dr Christensen arrived in Cape Town in June 1940 as ship's surgeon on a Danish cargo-liner. Denmark was under German control, and the ship came under command of the South African government for use in war operations. In October 1941, Christensen left the ship to become assistant to Dr Edmond Grasset of the South African Institute for Medical Research in Johannesburg. Later, Christensen was head of department and associate director. Grasset produced the Institute's first concentrated Bitis arietans-Naja nivea antivenom in 1932. When Grasset resigned in 1946, Christensen took over the venom research projects. He introduced changes and produced antisera of high quality. As the paraspecificity of the polyvalent antivenom was limited, Christensen increased the number of immunising antigens to allow treatment against the bite of the many species of viperid and elapid snakes in southern and equatorial Africa. Using pepsin-refined antiserum, Christensen isolated three toxic fractions from Naja nivea venom and showed how the presence of multiple toxins affected antivenom neutralisation curves and estimates of antivenom potency. A member of a WHO Expert Committee, he raised and tested for suitability, the first reference antivenom. Dr Christensen was acclaimed internationally for his expertise, and for his dedicated service to the treatment of snakebite.

Neurosurgical treatment for tetanus.

Soon after the discovery of the tetanus antitoxin, animal experiments led to the conclusion that intracerebral injection of the antitoxin would be useful in the treatment of tetanus. The French surgeon Quenu carried out the first injection and gave a description of the neurosurgical technique required. The method was applied in other European countries until it was declared to be less efficient than simple subcutaneous or intravenous injections. Outside Europe, intracerebral injections of tetanus antitoxin were reported and photographed in Montevideo, Uruguay, in 1901.

[The problem history of the toxin-antitoxin theory in medical microbiology]. / Zur Problemgeschichte der Toxin-Antitoxintheorie in der medizinischen Mikrobiologie.

The paper presents the history of the toxin-antitoxin theory. It covers the working hypotheses of the pathological-anatomical and clinical research (Virchow and Oertel), the experimental evidence of the diphtheria toxin by Roux and Yersin, up to the discovery of the antitoxin effect by Behring. The differences between an experimental based theory and the speculative conceptions of that time are discussed.