[A Japanese in Marburg : Excerpts from the Memories - Jiden - of the Japanese Bacteriologist Taichi Kitashima (1870-1956)]. / Ein Japaner in Marburg : Aus den Erinnerungen ­ Jiden ­ des japanischen Bakteriologen Taichi Kitashima (1870­1956).

The heart of this article is the transmission of selected chapters from the Japanese bacteriologist Taichi Kitashima's (1870-1956) autobiographical memoirs (in Japanese, Jiden) published in 1955, in which Kitashima reports on his stay in Marburg in a very personal and subjective way. Like other Japanese physicians of his generation, Kitashima spent several years in Germany in order to work with the serum researcher Emil von Behring and continued his education there. The contact came through Kitashima's teacher Shibasaburô Kitasato, who had worked with Behring in Berlin on questions of immunology. The memoir gives insight into Behring's laboratory work and his relation to his "subordinates". The editors investigate to what extent Kitashima's assessment, made from a distance of fifty years, of his stay in Germany as "wasted time" was accurate, given the advantages that arose from having been part of a vibrant European scientific community, including encounters in the Pasteur Institute in Paris, and why he cultivated his contacts with Germany and the Behring family during National Socialism.

Understanding the Snake Venom Metalloproteinases: An Interview with Jay Fox and José María Gutiérrez.

Jay W. Fox and José María Gutiérrez recently finished editing a Special Issue on the topic "Snake Venom Metalloproteinases" in Toxins. The Special Issue covers a wide range of topics, including the molecular evolution and structure of snake venom metalloproteinases (SVMPs), the mechanisms involved in the generation of diversity of SVMPs, the mechanism of action of SVMPs, and their role in the pathophysiology of envenomings, with implications for improving the therapy of envenomings. In this interview, we discussed with Jay W. Fox and José María Gutiérrez their research on the SVMPs and their perspectives on the future trends and challenges for studying snake venoms.

Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges.

The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using "gold-standard" methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted.

[The death of Cleopatra]. / Mort de Cléopâtre.

The image of a queen bitten by a snake is controversial and the facts, such as the swiftness of her death and her servants, and scientific experiments are in favour of a deadly poisoning. The author reminds that in the ancient texts the snake had sacred virtues and it was a symbolic image to embellish the suicide of the one who was sentenced to death by the Romans. Octaves set up the myth of a fatal bite which became an iconographic image for the cinema.

Twentieth century toxinology and antivenom development in Australia.

It was not until the last decade of the 19th century that an experimental approach (led by Bancroft in Queensland and Martin in Sydney and Melbourne) brought a higher plane of scientific objectivity to usher in the modern era of Australian toxinology. This Australia era, 1895-1905, coincided with and in some respects was the result of the new knowledge emerging from Europe and the Americas of the therapeutic effects of antitoxins. The subsequent systematic study of Australian venoms and toxins through to the 1930s and beyond, by Tidswell, Fairley, Ross, Kellaway and Cleland, set the foundation for Australia's leading reputation in venom research. As elsewhere, this development was to revolutionise the medical management of those victims who in the past had died in Australia from our venomous and toxic fauna. Morgan, Graydon, Weiner, Lane and Baxter at the Commonwealth Serum Laboratories emphasised the importance of cooperation between those expert at catching and milking the venomous creatures and those developing the antivenoms. Commercial antivenom manufacture began in Australia in 1930 with the tiger snake antivenom. This was followed by other antivenoms for the other important species (1955: taipan; 1956: brown snake; 1958: death adder; 1959: Papuan black snake; 1961: sea snake; 1962: polyvalent) including the first marine antivenoms in the world (1956: stonefish antivenom; 1970: box jellyfish) culminating, in 1980, with the release of the funnel web spider antivenom. More recent activity has focused on veterinary antivenoms and production of new generation human antivenoms for export (CroFab and ViperaTAB). This paper reviews some of the milestones of Australian toxinology, and antivenom development in particular, during the 20th century.

The pioneers of venom production for Australian antivenoms.

Before the introduction of the first Australian antivenom was the era of the self-styled 'snakemen' and their diverse snakebite remedies. Many received multiple bites from highly dangerous snakes, some of which were deliberately taken to either prove a certain treatment or liven up their show. The mortality rate among these handlers and showmen was high. Production of the first effective Australian antivenom, the tiger snake antivenom, in 1930, began the scientific approach to treating snakebite and opened new frontiers for professional and amateur snake people. Collecting venoms in the development and early production of antivenoms was carried out by a number of professional herpetologists often with little or no reward and in some instances at the ultimate cost of their lives. This paper reviews the most important of those late nineteenth and twentieth century snakemen and their contributions to venom research, antivenom production and current toxinological knowledge.

Karl Heinrich Slotta (1895-1987) biochemist: snakes, pregnancy and coffee.

In 1923 Karl H. Slotta obtained his PhD in chemistry from the University of Breslau, Germany, where he continued to work. At the instigation of the gynaecologist Ludwig Fraenkel, Slotta made the first isolation of progesterone in 1933. In 1934 he proposed the correct structural formula. Slotta was appointed professor of chemistry in 1935, but with the oppression of the Nazi regime mounting, he soon left Germany with his family to take a post at the Instituto Butantan, Brazil. Initially he worked on the chemistry of coffee. In 1938 Slotta and his brother-in-law Heinz Fraenkel-Conrat isolated crotoxin from Crotalus durissus terrificus venom, the first snake toxin to be obtained in crystalline form. They had evidence to suggest that the toxicity of crotoxin was due to a phospholipolytic action on nerve lipids. In 1938 Slotta's department was closed; he subsequently cofounded a biopharmaceutical company. In 1956 Slotta was appointed research professor of biochemistry at the University of Miami, USA. Slotta purified the most basic polypeptide from Naja naja venom, known as direct lytic factor, and with James Vick identified this as cardiotoxin. Karl H. Slotta will be remembered not only for his skill as a biochemist but also for his indomitable and cheerful spirit.

Maurício Rocha e Silva MD: snake venom, bradykinin and the rise of autopharmacology.

Maurício Rocha e Silva is well known as the discoverer of bradykinin, the powerful hypotensive and smooth muscle stimulating polypeptide which was first detected in plasma following the addition of Bothrops jararaca venom. The discovery in São Paulo, Brazil, in 1948 was the outcome of studies on proteolytic enzymes that Rocha e Silva started in 1939 at a time when circulatory shock was considered to be mediated by histamine. This line of research was prompted by the publications of Feldberg and Kellaway which identified the release of histamine and a slow-reacting substance (SRC-C) from isolated lungs perfused with Naja venom. Rocha e Silva was interested in determining whether trypsin-like enzymes, as shown for phospholipase, had a role in the release of histamine in shock. Instead, he and his co-workers demonstrated that such an enzyme released a new autopharmacological principle, bradykinin, from a plasma globulin precursor. Studies by Ferreira and Rocha e Silva on ways of blocking plasma kinin-destroying activity led Ferreira to isolate bradykinin-potentiating peptides from B. jararaca venom. These peptides were later shown to block angiotensin-I converting enzyme and so have an effect on hypertension. The discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena including circulatory shock induced by venoms and toxins.

Sir Joseph Fayrer MD FRS (1824-1907) Indian Medical Service: snakebite and mortality in British India.

Whilst Professor of Surgery at the Calcutta Medical College, Dr Fayrer studied all aspects of snake poisoning. His work, The Thanatophidia of India being a Description of the Venomous Snakes of the Indian Peninsula, with an Account of the Influence of their Poison of Life; and a Series of Experiments was published in 1872. Collating information from official Government records of death due to snakebite, Fayrer recorded a mortality of 11,416 persons for the year 1869 in the Presidency of Bengal and estimated a mortality of more than 20,000 for all British India. In 1872, working in London with Lauder Brunton, Fayrer studied the physiological action on Naja naja venom in more detail. Respiratory paralysis was due to a curare-like blockade of the neuromuscular junction, and they believed, a central effect also; artificial respiration was ineffective in producing recovery. A large dose of cobra venom was observed to induce tetanic contraction of the heart both in vivo and in vitro. As President of the Medical Board of the India Office in London from 1873 to 1895, Sir Joseph Fayrer was much concerned with cholera epidemics which resulted in an average mortality of over 200,000 persons annually. In 1885, he represented the Indian Government at the fourth International Conference on Cholera, a fore-runner of the World Health Organization.