Bizzozero, Giulio Cesare

(b. Varese, near Milan, Italy, 20 March 1846; d. Turin, Italy, 8 April 1901)

histology.

Bizzozero was the son of Felice Bizzozero, a small manufacturer, and Carolina Veratti. After studying classis at Milan, he went to Pavia for medical study and received the M.D. in 1866. Upon graduation, Bizzozero enlisted in the army of Garibaldi as a military physician. The war against Austria ended within the year, and in 1867 he was appointed substitute professor of general pathology at the University of Pavia. He taught there until 1872; in that year Bizzozero became ordinary professor of general pathology at Turin. For almost thirty years he was a well known teacher and researcher at Turin. Among the more illustrious of his puplis were Camillo Bozzolo, Camillo Golgi, Pio Foá, Gaetano Salvioli, and Cesare Sacerdotti. The school of Bizzozero in Turin and later, the school of Alessandro Lusting in Florence were the first Italian teaching centers in general pathology.

A man of wide medical learning, Bizzozero was among the first to understand the importance to medicine of the microscope. In 1878 he instituted an annual course in clinical microscopy as an aid to the exhaustive study of sick persons. In 1879 he published his Manuale di microscopia clinica, later reprinted many times and translated into German. Three years before, Bizzozero had founded the Archivio per le scienze mediche. Stricken, after 1890, by a distressing debility of the right eye, he was unable to continue his own microscopical observations. He therefore devoted himself more and more to writing works that would develop an awareness of the need for public health measures. As early as 1883 Bizzozero set forth his program: the defense of mankind against infectious diseases. In 1890, he was appointed a senator.

Bizzozero was trained in scientific research by Eusebio Oehl, director of the laboratory of experimental physiology of Pavia University, and by Paolo Mantegazza, who in 1861 had founded the laboratory of general pathology at Pavia, the first in Italy. But the direction of Bizzozero’s research was morphological. From his first paper in 1862 to his last paper in 1900, he was, essentially, a histologist. Bizzozero was so convinced of the importance of microscopical morphology that in 1880 he began, his own intiative, to teach normal histology at Turin, a tree course which he continued until his death.

Bizzozero was, undoubtedly, one of the outstanding histologists of his time. Of highest impotance were his work on epithelial epithelial tissues—for instance, his studies of stratified squamous epithelium in 1870 and 1886—but even earlier there was his paper of 1864, “Delle cellule cigliate del reticolo malpighiano dell’ epidermide,” in which he demonstrated the connections between the cells of the Malpighian layer. In collaboration with Gaetano Salvioli, Bizzozero defined the mesothelium of the great serous membranes (pleural and peritoneal) as a continuous layer, without stomata, separating the serous cavity from the lymphatic vessels. He also published studies (1888–1893) on the gastric and intestinal glands of mammals. Bizzozero thus contributed decisively to epithelial histology, fundamental knowledge of which had begun with the work of Jacob Henle.

Equally important were Bizzozero’s observations on connective tissue: he illustrated (1865, 1872, 1873) the cells of the meninges and showed that tumors of the meninges (meningiomas) arise from the connective tissue cells of the meninges proper, not from the endothelial cells of blood vessels. In the structure of tendons he showed that the tendinous cells are in direct contact with the collagenous fibers. Special attention should be given to his work on the structure of the lymphatic glands. In 1872 Bizzozero clarified the peculiarity of cytoplasmatic relations between the cells and the fibers of the reticulum: “The cells are only applied on the reticulum, and they do not take integrated part in the constitution of reticulum.” Bizzozero also anticipated actual knowledge of the “reticular cell,” the staminal element of lymph nodes which he first called cellula del reticolo. He defined the important morphological problem of the sinuses of lymph nodes, demonstrating the existence of endothelial cells (reticuloendothelial cells) on the internal wall of sinuses. In 1868 Bizzozero demonstrated the erythrocytopoietic function of bone marrow, which he illustrated in several works, and in 1869 he discovered the megakaryocytes.

Bizzozero then undertook the solution of very important biological problems. In his first experimental work (1866) he demonstrated that granulation tissue originated as a consequence of the proliferative activity of mobile cells of loose connective tissue proper—cells which, for their high potentiality, he termed “embryonal cells” of loose connective tissue. Bizzozero also delineated the morphology of these “wandering polyblastic cells,” knowledge of which was developed from 1902 to 1906 by the Russian histologist Alexander Maximov. Moreover, in this work Bizzozero demonstrated that in the neoproduction of granulation tissue there is also a neoproduction of capillaries; he described their development from compact cellular cordons in which a vascular cavity appears secondarily. This important observation was confirmed in 1871 by Julius Arnold in his Experimentelle Untersuchungen über die Blutcapillaren.

With his work on granulation tissue, Bizzozero was, with Virchow and Cohnheim, among the pioneers in the modern study of inflammation. Bizzozero’s observations went further, however, for he first illustrated the power of ingestion (phagocytosis) as characteristic of the great mobile cells of loose connective tissue, of similar cells of bone marrow, and of the reticular cells of lymph nodes—a capacity to ingest damaged cells as well as the products of an inflammatory process: “The celluliferous cells [macrophages containing dead leukocytes] are large cells of connectival origin, which introduce into the proper contractile protoplasm the pus corpuscles [leukocytes]…. The finding of these celluliferous cells is not interpretable as a process of ‘endogenesis’ [as Rudolf Virchow then thought in his erroneous doctrine of endogenous cell formation], but as the effect of ingestion of pus corpuscles…. These great celluliferous cells unquestionably possess the power to devour pus corpuscles, erythrocytes, pigment granules.”

In 1873 Bizzozero affirmed, ten years before Metchnikoff, that connective tissue cells (reticular cells of lymph nodes) act also against infection: “These cells, which contain granules of cinnebar or China ink 2–3 days after the injection in the subcutaneous connective tissue of those substances, constitute a very intricate labyrinth, through which the liquid carried from the lymphatic vessels is obliged to flow, and the corpuscles carried by the liquid, coming in contact with the protoplasm of reticular cells, are ingested by them. This fact is, perhaps, the cause of stoppage of some infections in the lymph nodes in which the lymphatic vessels arrive from the part overwhelmed by infection’s products.”

Although the name of Bizzozero is not linked with phagocytosis today, it is associated with the platelets. Knowing that Max Schultze in 1865 had described the presence, in the blood of healthy man, of irregular accumulations which he termed “granular formations,” Bizzozero demonstrated in 1882 that they were normal elements of the blood and that they were linked to the phenomenon of thrombosis—hence their name of “thrombocytes.”

BIBLIOGRAPHY

I. Original Works. Bizzozero’s works are collected in Le opere scientifiche di Giulio Bizzozero, 2 vols. (Milan, 1905), with a preface by Camillo Golgi, which contains all of Bizzozero’s works, complete with original illustrations. For Bizzozero’s research on thrombocytes, see especially his “Di un nuovo elemento morfologico del sangue e della sua importanza nella trombosi e nella coagulazione del sangue,” in Archives italiennes de biologie, 2 (1882), 345–365; and “Ueber einen neuen Formbestandteil des Blutes, und dessen Rolle bei der Thrombose und der Blutgerinnung,” in Virchow’s Archive, 90 (1882), 261–280. He also published a short book: Di nuovo elemento morfologico del sangue… (Milan, 1883).

II. Secondary Literature. Works on Bizzozero are R. Fusari, “Giulio Bizzozewro,” in Monitore zoologico italiano, 12 (1901), 103–107, a complete list of his work; and P. Franceschine, “La conoscenza dei tessuti connettivi nelle ricerche di Giulio Bizzozero,” in Physis, 4 (1962), 227–267, which includes an extensive bibliography.

Pietro Franceschini