Giovanni Battista Grassi

Grassi Giovanni Battista

Grassi's earlier works were on anatomy and then entomology. He studied the development of the vertebral column in bony fishes and also endemic goiter. His studies on bees, myriapods and termites were monumental. He also studied the chetognates and the reproduction of eels, and he described a new species of spider, Koenenia mirabilis in 1885, dedicated to his wife.

He also made significant contribution to the study of the phylloxera of grapes, which he pursued for several years. The notes of his observations La questione fillosserica in Italia (1904) influenced the Italian Ministry of Agriculture, which eventually requested him to do an exhaustive study of this subject. In 1912 he produced a monumental investigation of the morphology and biology of the Italian and other European genera of phylloxera. It was a foundation for systematic control of agricultural pests.[3]

In 1876 Grassi investigated his native hometown Rovellasca for the high mortality of cats and discovered that they were heavily infected with the nematode Dochmius balsami. In 1878, while still a student at the University of Pavia, he discovered anchylostomiasis in Italy from by identifying the eggs from the faeces of infected individuals. He continued to make great impacts on the study of Anguillula intestinalis, filarial worms, Trichocephalus dispar, and Bilharzia. He was the first to show that the human dwarf tapeworm Taenia nana is able to go through its entire life cycle in one animal, without the need of an intermediate host, a notion that had long been rejected. He was also the first to show that the flea Pulex serraticeps is the intermediate host of feline tapeworm Taenia elliptica. Thus he proposed that swallowing of infected fleas (for example, with milk) might be the reason for taeniasis in children.[3] In 1879 he published a work on the life cycle of Strongyloides stercoralis, and erected the genus Strongyloides. In 1890 he, with Salvatore Calandruccio, described Dipetalonema reconditum, a non-pathogenic filarial worm of dogs, and showed that the parasite completed its development in human fleas, Pulex irritans.[1]

The first crucial step in understanding the life cycle of the roundworm Ascaris lumbricoides was demonstrated by Grassi in a grotesque self-experimentation. To solve a century-old puzzle of how infection of roundworm is transmitted from one host to another, he ingested the roundworm eggs on 30 August 1879. He had obtained the eggs from a human corpse, which was heavily infected, upon autopsy on 10 October 1878.[6] After twenty-two days, he found fresh eggs in his faeces. Thus proving that the roundworm is transmitted through direct ingestion from contaminated source.[7][8]

Grassi made his first contribution on malaria in 1890, when he (with Raimondo Feletti) discovered Haemamoeba vivax, later renamed Plasmodium vivax. He described Proteosoma praecox, the malaria parasite of birds. In 1891 he performed the first inoculation of malaria parasites from one bird into another. He was the first to compile a comprehensive monograph on the identity and impact of different malarial parasites. His work Studi di uno Zoologo Sulla Malaria in 1891 is as relevant today as it was in his time. His description of the specific characteristics responsible for benign tertian (Haemamoeba vivax), malignant tertian (Laverania malariae, renamed P. falciparum) and quartan (Haemamoeba malariae, renamed P. malariae) malaria resolved the confusion of the time. In addition, his monograph also presented the first conclusive depiction that the bite of only female Anopheles mosquitoes could transmit malaria. In a classic experiment, he dispatched 112 volunteers to the Capaccio plains, a malaria-endemic area, protected them from mosquito bites between dusk and dawn, and they did not get malaria (except five of them) compared with 415 unprotected volunteers who all contracted malaria. In 1898 he and Bignami were able to produce the final proof of mosquito transmission of malaria when they fed local mosquitoes (A. claviger) on infected patients and found that uninfected individuals developed malaria through the mosquito bite.[9]

The 1902 Nobel Prize in Physiology or Medicine was awarded to Ronald Ross for his discovery of the life cycle of malarial parasite (or as the Nobel citation goes: for his work on malaria, by which he has shown how it enters the organism...). However, this was disputed and continues to be disputed to this day. Grassi was the first to suggest that there must be some developmental stage of Plasmodium in the white blood cells. In 1897, he and his associates established the developmental stages of malaria parasites in anopheline mosquitoes; and they described the complete life cycles of P. falciparum, P. vivax and P. malariae the following year.[10] When the Nobel nomination was called, there began a fiery polemic over priority between him and Ross. The situation was worsened with the involvement of Robert Koch. The initial opinion of the Nobel Committee was that the prize should be shared between Ross and Grassi. Then Ross made a defamatory campaign accusing Grassi of deliberate fraud. Koch was appointed as a "neutral arbitrator" in the committee, and as reported, "[He] threw the full weight of his considerable authority in insisting that Grassi did not deserve the honor" (Grassi would later point out flaws in Koch's own methodology on malarial research).[11] Ross was the first to show that malarial parasite was transmitted by the bite of infected mosquitoes, in his case the avian Plasmodium relictum. But Grassi's work revealed that human malarial parasites were carried only by female Anopheles. He identified the mosquito species correctly, in his case P. claviger. By today's standard, they are likely to have shared the Nobel prize.[2][12]

Grassi had developed a dogma that "there is no malaria without Anopheles" or simply, "anophelism without malaria". This was dubbed "Grassi's Law", which is formulated as: infected man + anopheles mosquitoes = malaria. Although the equation is straightforwardly correct, the reverse implication is not so. In many areas, he himself had noted that where anopheline vectors were abundant, malaria was not at all prevalent, and sometimes absent. This caused a little problem in understanding malaria epidemiology for some time. In fact, in 1919 he identified three typical malaria-prevalent localities which were not affected by malaria in the same way: the gardens of Schito near Naples, Massarosa in Tuscany, and Alberone in Lombardia. In 1921, after repeated assessment, he concluded with the assumption of the existence of races of Anopheles that there were morphologically indistinguishable mosquitoes that do not bite humans and therefore did not play a role as vectors.[13][14] The enigma was solved in 1925, a year after his death, by his pupil Falleroni, who demonstrated that there are six cryptic species, of which only four bite humans and transmit malaria.[4]