Grassi versus Ross: who solved the riddle of malaria?

ed by Mercè Piqueras, INTERNATIONAL MICROBIOLOGY, from a lecture given by the author at the Institute for Catalan Studies, Barcelona, on October 19, 2005. 70 INT. MICROBIOL. Vol. 9, 2006 In 1879, Patrick Manson (1844–1922), a Scottish physician who had worked in China for over 20 years, demonstrated that so-called Bancroft’s filaria (Wuchereria bancrofti) was transmitted via the bite of a mosquito of the genus Culex. He proposed that a mosquito of that genus should be also involved in malaria, but as part of a bizarre cycle: the parasites were released in water by dead mosquitoes and then transferred to humans when they drank the water. Manson corresponded extensively with Ronald Ross, including 173 letters (gathered in a book in 1998) in which he followed and steadily guided Ross’s progress in the study of malaria in India. Ronald Ross (1857–1932) is the main character in the history of British malarial research. Born in India, he joined the army as an officer of the Indian Medical Service. In 1897, when he studied malaria in birds, he described oocysts of the malarial parasite in the walls of the stomach of an unclassified mosquito (“a grey mosquito, a dappled winged mosquito”), which he thought was probably Culex. This was the starting point of Ariadne’s thread that would eventually lead to the exit from the labyrinth of malaria. A map of Italy published in 1882 indicated in red the areas with widespread malaria and in yellow the areas where the disease was present. The red area included vast coastal areas of Tuscany (Maremma), Latium (Roman plain and Pontine marshes), and Campania. Also at high risk of malaria were the Venetian lagoon areas, the Po River Delta, the Ionian Coast of Calabria, and the coasts of Sardinia and Sicily. Even more tragically amazing is another map, published in 1899, that was produced by a professor of hygiene, Augusto Celli, which indicated those railway lines where the risk of contracting malaria during a train trip was high! Italian physicians thus experienced malaria as a daily domestic tragedy, and were highly motivated to solve the mystery of the origin and transmission of the disease. First malaria studies in Italy The death from malaria of a nine-year-old boy in Rome at the turn of the twentieth century spurred several Italian physicians to carry out research aimed at solving the riddle of the cause of the disease. I will mention only a few eminent figures. Ettore Marchiafava (1847–1935) and Augusto Celli (1857– 1914), both from the Faculty of Medicine of Rome, believed that the pathogenic factor of malaria was a bacterium, Bacillus malariae. After careful studies, however, they agreed with Laveran and recognized the protozoan nature of the malarial parasite. They proposed the name Plasmodium for the protozoan identified and named by Laveran. In fact, in 1885, Oscillaria had been assigned to another organism, a “blue-green alga” (currently a cyanobacterium). Marchiafava and Celli also identified two species of Plasmodium, P. falciparum and P. vivax. Camillo Golgi (1843–1926), Professor of General Pathology at the University of Pavia, in northern Italy, is well-known worldwide for his research in the physiology of the nervous system (he was awarded the 1906 Nobel Prize in Physiology or Medicine, together with Santiago Ramón y Cajal). Nevertheless, he was also deeply involved in malaria research. Indeed, residents of the agricultural areas along the Po River had a high risk of the disease, especially where there were extensive rice fields, such as the countryside around Pavia. Golgi made a notable contribution to malariology by relating the clinical sign of the fever episode with the schizogonic phase of the plasmodium, and by showing that the so-called tertian and quartan intermittent fevers are due to the presence in the blood of two different Plasmodium species (P. malariae and P. vivax), sometimes present together. Last, but certainly not least, is Battista Grassi (1854– 1925), the other main character in this story. Grassi (Fig. 1) was born in Rovellasca, a rural town not far from Milan. Even though he graduated in Medicine at Pavia, he felt driven to become a zoologist because of his frequent contact with nature during his childhood and adolescence and because the University of Pavia was, at the time, the “sun of Italian biology”, as Grassi himself used to say. After graduation, he worked at the Naples Zoological Station, founded by Anton Dohrn (1840–1909), and at the Messina oceanographic station of Nicolaus Kleinenberg (1842–1897). His training was completed at the University of Heidelberg under the guidance of two great scientists: Carl Gegenbaur (1826–1903), who reorganized comparative anatomy in Darwinian terms, and Otto Bütschli (1848–1920), one of the greatest experts on protozoans. At a very young age, Grassi became Professor of Zoology at Catania and was already famous for two extensive monographs, one on the Chaetognatha and the other on the vertebral column of fishes.