ARTHUS, NICOLAS MAURICE

(b. Angers, France, 9 January 1862; d. Fribourg, Switzerland, 24 February 1945)

physiology.

The son of Nicolas Arthus, a leather merchant, and of Marie Adélaïde Manuelle. Arthus prepared for the entrance examination for the École Polytechnique, then studied physiology, physics, and medicine at the Sorbonne. He became a pupil of the physiologist Albert Dastre and his technical assistant from 1887 to 1895. His first research papers (1889) concerned glycogenesis and were written with Dastre. In November 1890, he presented a doctoral dissertation in natural science on blood clotting, Recherehes sur la coagulation du sang. Drawing a close analogy between blood and milk, Arthus discovered that calcium was a necessary component of milk clotting, a fact that had recently been shown for blood clotting. Both blood and milk clotting also require a ferment. Arthus worked on the chemistry of milk and blood proteins, and on the physiology of milk digestion and of milk and blood clotting. In the summer of 1892, he visited the physiological chemistry laboratory of Wilhelm Friedrich kühne in Heidelberg.

In 1893 Arthus presented a doctoral dissertation in physics, Recherehes sur quelques substances albuminoïdes. La classe des caséines, la famille des fibrines. He studied the comparative chemistry of casein and fibrin and showed that they had different coagulation properties. In 1894 he published a book on these topics, Coagulation des liquides organiques. He continued to work on milk clotting and discovered in 1903 that the secretion of the milk-clotting ferment is triggered by the presence of milk in the stomach. But he concentrated mainly on blood coagulation, a topic to which he made several valuable contributions. In 1901 and 1902 he studied the coagulation-preventing properties of sodium citrate, a subject that acquired much therapeutic importance. He also studied the time variations of coagulation speed and fibrin-ferment secretion. His blood-clotting studies, covering the period from 1890 to 1908, are of equal interest for physiology and for surgery.

Arthus also studied the activity of such proteolytic enzymes as trypsin. In 1896 he presented a medical dissertation. Nature des enzymes. Pointing out that the analytical chemistry of proteins was in a state of utmost confusion, Arthus advocated the view, already formulated by L. de Jager, that enzymes were not chemical compounds but “properties” or agents resembling physical processes (such as light or magnetism) that trigger chemical effects on their substrates—a concept that turned out to be misleading.

After serving as a lecturer in physiology at the Sorbonne (1890–1895), Arthus was appointed professor of physiology, physiological chemistry, and general microbiology at the University of Fribourg in 1895. In 1900 he was appointed laboratory director at the Pasteur Institute in Lille, which was headed by Albert Calmette. At that time he did mainly studies on blood and on toxic proteins. In 1903 he was given the position of lecturer at the medical school of the University of Marseilles and in 1907 was appointed professor of physiology and director of the Physiological Institute at the University of Lausanne, a position he held until his retirement in 1932.

In 1902 Charles Richet and Paul Portier reported to the Société de Biologie their discovery of anaphylaxis, the increased sensitivity of an organism to several contacts with poisonous substances, which were given in low, nontoxic doses. They coined the word anaphylaxie, meaning that the organism’s defense was lowered in this state. Thenew phenomenon aroused much interest and some controversy. Independently, Arthus was working on an organism’s reaction to proteins of other animal species. In order to recognize these heterologous proteins, he needed a precipitating serum, which he prepared by using horse serum repeatedly injected into rabbits, thus producing the precipitation reaction in the rabbit’s serum. In spite of rigorous asepsis, he observed local edema and necrosis. In order to avoid these problems, he used intravenous injections in the same rabbits, which died after a few minutes. Intravenous injections of horse serum into unsensitized rabbits never created such problems. Arthus then compared his fortuitous discovery with Richet and Portier’s recent report of anaphylaxis. The phenomenon of local anaphylaxis, or Arthus’ phenomenon, was reported to the Société de Biologie in 1903. Arthus’ use of Richet’s terminology for a slightly different phenomenon led him to the concept of serum anaphylaxis.

In Sir Henry Dale’s view, Arthus’studies, together with other studies on the guinea pig, contributed to a better interpretation of anaphylaxis, which does not consist of a decrease in the organism’s defense but of an increased sensitivity. Arthus tried to answer the question of whether the tissue lesions resulted from a precipitate within the organism. In 1909 he described the anaphylactic properties of blood serum proteins and of other proteins, such as ovalbumin. He debated with Richet about the specificity of the anaphylactic reaction and noted that the local reaction is not specific in the rabbit, while in species that do not present any local reaction, such as the dog, the anaphylactic syndrome is specific. From the study of a rather peculiar case, the rabbit’s anaphylaxis, Arthus came to the conclusion that anaphylaxis and immunity are different phenomena. In contrast, in 1910 Pierre Nolf maintained that anaphylaxis and immunity were expressions of the same state of the organism. In Arthus’ view, the rabbit’s local reaction did not result from a blood precipitate. In 1910 Arthus made use of more specific tools, the snake venoms, in order to better analyze the relationships among anaphylaxis, protein poisoning, and immunity. In his view, anaphylaxis was a phenomenon of poisoning by heterologous proteins rather than a sign of immunity.

Snake venoms, Arthus thought, were able to produce both anaphylactic and immune reactions. He tested all sorts of venoms, did thorough physiopathological studies, and quantitatively studied the neutralization of venoms by serums. He distinguished between several properties of the venoms and demonstrated that cobra venom acts like curare. He showed that other venoms have coagulating properties, or depressing properties on cardiac rhythm or blood pressure. But since Arthus was primarily interested in the distinction that he thought had to be established between anaphylaxis and immunity, he concentrated on the anaphylactic syndrome, or protein poisoning, and on immunity, two phenomena that may be produced by several injections of small doses of venoms. In the rabbit Arthus observed the increased sensitivity to protein poisoning that is characteristic of anaphylaxis and the absence of more specific symptoms like curare paralysis, which is a sign of immunity. Discussing Nolf’s experiments, he reviewed the body of evidence in his 1921 book De l’anaphylaxie à l’immunité. Arthus, who strongly distrusted theories, was perhaps the victim of the peculiarities of the phenomenon he had discovered in the rabbit. Later, Arthus continued to work on venoms. He showed that attenuated venoms, which are no more toxic, can still produce anaphylactic reactions.

Along with his basic research in experimental physiology, Arthus was deeply committed to teaching, which in his view included the writing of textbooks. A tireless experimentalist and a philosopher of the experimental method, he was also a tireless writer. His textbook Éléments de chimie physiologique (subsequently Précis de chimie physiologique) had eleven editions between 1895 and 1932. It was translated into German and Spanish. His textbook Éléments de physiologie (later Précis de physiologie) had seven editions between 1902 and 1927. He also published La physiologie in 1920 and Précis de physiologie microbienne in 1921.

Arthus retired from his chair in Lausanne in 1932. Since working facilities were no longer available to him, he returned to Fribourg, where he was given the directorship of the Institute of Bacteriology and Hygiene, a position he held until 1942. He died in his eighty-fourth year.

BIBLIOGRAPHY

I. Original Works. Recherehes sar la coagulation du sang (Paris, 1890); Recherches sur quelques substances albuminoïdes. La classe des caséines, la famille des fibrines (Paris, 1893): Coagulation des liquides orgainiques. Sang, lymphe, transsudats, lait (Paris, 1894); Éléments de chimie physiologique (Paris. 1895), continued as Précis de chimie physiologique (11 th ed., Paris, 1932); Nature des enzymes (Paris, 1896); La coagulation du sang (Paris, 1899); Éléments de physiologie (Paris, 1902), continued as Précis de physiologie (7th ed., 1927); “Injections répétées de sérum de cheval chez le lapin,” in Comptes-rendus de la Société de biologie55 (1903), 817–820: “Lésions cutanées produites par les injections de sérum de cheval chez le lapin anaphylactisé par et pour ce sérum, en collaboration avec Maurice Breton,” ibid., 55 (1903), 1478–1480.

“Sur la séroanaphyluxie du lapin,” ibid., 60 (1906), 1143–1145. “La séroanaphyluxie du lapin,” in Archives nternationales de physiologie, 7 (1909), 471–526; “Sur la séro-anaphylaxie,” in Presse médicale, 5 (1909), 305– 306; “Le venin de cobra est un curare,” in Archives internationales de physiologie, 10 (1910), 161–191; “De la spécificité des sérums antivenimeux,” ibid., 11 (1912), 265–338; “Études sur les venins de serpents,” ibid., 12 (1912), 162–177, 271–288, 369–394; “Anaphylaxie-immunité,” in Comptes-rendus de la Société de biologie, 82 (1919), 1200–1202; La physiologie (Paris, 1920); De l’anaphylaxie à l’immunité (Paris, 1921); Précis de physiologie microbienne (Paris, 1921); and “Pour mieux connaître les anatoxines,” in Bruxelles médical (1930), 1–13.

II. Secondary Literature. Obituary by Léon Binet, in Bulletin de l’Académie de médecine, 129 (1945), 374–376, and by Henri Roger, in Presse médicale, 53 (1945), 261–262. See also Daniel Bovet, Une chimie qui guérit. Histoire de la découverte des sulfamides (Paris, 1988); Henry Dale, “Mécanisme de l’anaphylaxie,” in Presse médcale, 60 (1952), 680–682; and Guy Saudan, “La physiologie à la haute école de Lausanne: Le premier demi-siècle (1881–1932),” in Gesnerus, 45 (1988), 263–270.

Claude Debru