NEGRI, ADELCHI

(b. Perugia, Italy, 2 August 1876; d. Pavia, Italy, 19 February 1912)

pathology.

Negri studied medicine and surgery at Pavia University, where, as a resident student, he worked in the pathology laboratory directed by Camillo Golgi. After graduating with honors in 1900, he became Golgi’s assistant. He was named lecturer in general pathology in 1905 and in 1909 was appointed to teach bacteriology, thus becoming the first official teacher of that subject at Pavia. In 1906 he married his colleague Lina Luzzani and six years later, at the age of thirty-five, died of tuberculosis.

Trained in Golgi’s school, Negri conducted research in histology, hematology, cytology, protozoology, and hygiene. His fundamental scientific contribution was the discovery, announced to the Pavia Medical Society on 27 March 1903, of the rabies corpuscles, now known as “Negri bodies.” During histological research undertaken to clarify the etiology of rabies and performed on Golgi’s advice, Negri found that in animals suffering from rabies, certain cells of the nervous system, especially the pyramidal cells of the horn of Ammon, contain endocellular bodies with an internal structure so evident and regular as to constitute a characteristic feature. These bodies consist of single or multiple eosinophile, spherical, ovoid, or pyriform endocytoplasmic (never endonuclear) formations with a well-defined outline, varying in size from two to more than twenty microns (apparently in proportion to the size of the animal) and containing minute basophil granules having a diameter of 0.2-0.5 micron.

This cytological phenomenon proved to be almost constant and was found typically and abundantly in the histological material from living victims of advanced spontaneous rabies (street virus) or from those who had died of it. On the other hand, it was absent or very rare in cases of infection following inoculation of fixed virus. Rabbits and dogs infected experimentally with the street virus, dogs dead from spontaneous rabies, a cat infected experimentally by subdural injection, and one human case (a woman of sixty-four who had died of rabies after being bitten by a rabid dog) furnished the material on which Negri gave the first demonstrations of his discovery.

From the beginning Negri believed that the endocellular bodies he had observed in the nerve cells were the pathogenic agents of rabies and that they were forms belonging to the developmental cycle of a protozoan, the systematic position of which he could not define. This opinion, which Negri never abandoned, immediately became the object of scientific discussion. Some months after Negri’s discovery, Alfonso Di Vestea in Naples, and Paul Remlinger and Riffat Bey in Constantinople, showed that the etiological agent of rabies is a filterable virus; and the argument about the significance of Negri’s bodies became wider and more intense, with eminent parasitologists taking conflicting positions. Even today, despite research with the electron microscope, the significance of Negri’s bodies has not been definitively clarified. Thus, as Luigi Bianchi wrote, it is still possible to accept Emilio Veratti’s opinion that Negri’s bodies are to be interpreted as specific formations closely linked to the virus and not as products of the cell containing it, without thereby assuming that they constitute the sole, infallible manifestation of the virus.

The specificity of Negri’s bodies and their importance for diagnosis are universally recognized; the search for them, however, has absolute probative value in diagnosis only when there is a positive result. Negri himself indicated the rules to be observed in identifying the bodies for diagnostic purposes in animals suspected of rabies. The bodies, in material simply fixed for eighteen to twenty-four hours in Zenker’s fluid and delicately pulped between cover glass and slide in a drop of glycinerinated water, appear under small enlargement as light yellow, glassy formations in the cytoplasm of the pyramidal cells; at enlargements of 400–600 diameters they reveal their characteristic internal structure.

BIBLIOGRAPHY

I. Original Works. Negri produced some thirty publications, some of them joint works, which appeared in Italian and foreign journals between 1899 and 1911. They are listed in Veratti’s article (see below) and in Archives de parasitologie,16 (1913), 166. Documentary material concerning Negri is kept in the Museum of University History, Pavia.

II. Secondary Literature. See Luigi Bianchi, “Rabbia,” in Paolo Introzzi, ed., Trattato italiano di medicina interna, pt. 4, Malattie infettive e parassitarie, II (Bologna, 1965), 1351–1364; and I corpi del Negri nello sviluppo della microbiologia all’ Università di Pavia (Pavia, 1967); and Emilio Veratti, “Adelchi Negri. La vita e l’opera scientifica,” in Rivista di biologia,16, no. 3 (1934), 577–601.

Bruno Zanobio