Джованни Баттиста Грасси: Паразитолог және малярия зерттеушісінің өмірі мен еңбектері

Italian physician and zoologist (1854–1925)

Giovanni Battista Grassi (27 March 1854 – 4 May 1925) was an Italian physician and zoologist, best known for his pioneering works on parasitology, especially on malariology. He was Professor of Comparative Zoology at the University of Catania from 1883, and Professor of Comparative Anatomy at Sapienza University of Rome from 1895 until his death. His first major research on the taxonomy and biology of termites earned him the Royal Society's Darwin Medal in 1896. Grassi's scientific contributions covered embryological development of honey bees, on helminth parasites, the vine parasite phylloxera, on migrations and metamorphosis in eels, on arrow worms and termites. He was the first to demonstrate the life cycle of human dwarf tapeworm Taenia nana, and that this tapeworm does not require an intermediate host, contrary to popular belief. He was the first to demonstrate the direct life cycle of the roundworm Ascaris lumbricoides by self experimentation. He described canine filarial worm Dipetalonema reconditum, and demonstrated the parasite life cycle in fleas, Pulex irritans. He invented the genus of threadworms Strongyloides. He named the spider Koenenia mirabilis in 1885 after his wife, Maria Koenen. He pioneered the foundation of pest control for phylloxera of grapes. The most important contributions of Grassi are on malariology, discovering different species of malarial parasites in birds and humans, and their transmission. With Raimondo Feletti, he discovered Haemamoeba praecox and H. relictum (now under the genus Plasmodium) in birds. They correctly described Haemamoeba malariae and H. vivax (both now under Plasmodium), which became fundamental to clinical distinction of different human malaria: benign tertian caused by P. vivax, malignant tertian by P. falciparum and benign quartan by P. malariae). He was the first to describe and establish the life cycle of the human malarial parasite, Plasmodium falciparum, the most prevalent and deadliest species. He discovered that only female anopheline mosquitoes are capable of transmitting the disease. Grassi's works in malaria remain a lasting controversy in the history of Nobel Prizes. Since the inception of Nobel Prizes in 1901 until his death, he was nominated 21 times. For the 1902 Nobel Prize in Physiology or Medicine, he was nominated alongside French physician Charles Louis Alphonse Laveran, who discovered P. falciparum, and British army surgeon Ronald Ross. He and Ross were shortlisted for the final award, but Ross who appeared to have make the least important discovery, the transmission of malarial parasite in birds, was the sole winner. Grassi, who demonstrated the complete route of transmission of human Plasmodium, and correctly identified the types of malarial parasite as well as the mosquito vector, Anopheles claviger, was denied.

Grassi was born in Rovellasca, Italy, in what is now the Province of Como. His father Luigi Grassi was a municipal official, and mother Costanza Mazzuchelli was a noted peasant of unusual intelligence. He completed elementary education at Bolchi Stucchi private school in Saronno, and secondary education at Volta high school in Como. From 1872 he studied medicine at the University of Pavia under professors Camillo Golgi and Giulio Bizzozero and graduated in 1878. After graduation he worked first at Messina in the Naples Zoological Station and the Oceanographic Station founded by Nicolaus Kleinenberg and Anton Dohrn where he studied Chaetognatha, While in Heidelberg, he met a fellow student Maria Koenen whom she married in 1879. In 1883, he became Professor of Comparative Zoology at the University of Catania, He also began to study malaria working with Raimondo Feletti on malaria, discovering the parasite species of human and bird malaria. Grassi spent much of his later years in Fiumicino, a commune in the province of Rome, where his family had settled. There, he built a private clinic for children with malaria, and which he bestowed to her daughter Isabella for continued service after his death. Following his will, he was interred at a village cemetery in Fiumicino, as he achieved his most important medical services there. His wife Maria (1860–1942) and daughter were also interred at the same tomb.

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. The arrow worms were later classified as a separate phylum Chaetognatha, and are recognised as "enigmatic" animals. His associate Salvatore Calandruccio collected an unusual spider from Mount Etna in Sicily. Grassi identified it as not only new species but as belonging to a new family, and gave the name, 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. After twenty two days, he found fresh eggs in his faeces. Thus proving that the roundworm is transmitted through direct ingestion from contaminated source. In 1879, Grassi became the first to identify protozoans similar to amoebas from the human excreta. He gave a vivid description of the then named Amoeba coli, later classified as Entamoeba coli, which he considered to be harmless parasites as he found them from both sick and heathy individuals. At the time, these protozoans were believed to be pathogenic parasites like other amoebas. and closely related to the pathogenic species, E. histolytica. His report in 1885 showed the role of commensal protozoans in the digestion process of food in termites. and later found to infect humans as well.

Grassi started to study malaria in 1888 while at the University of Catania, with a colleague Raimondo Feletti. Laveran gave the name Oscillaria malariae, which was ultimately changed to Plasmodium falciparum by the International Commission on Zoological Nomenclature (ICZN) in 1954. Grassi and Feletti made the second discovery the next year that the harmless form of malaria was caused by a very similar protozoan which they named Laverania malariae (the genus name honouring Laveran). They reported the discovery in the December issue of Riforma Medica as "Sui Parasiti della Malaria" (On the Parasite of Malaria). The sequel report in 1890 described the discovery of the third human malarial parasite which they called Haemamoeba vivax. Along with the new description indicating obvious relationship between the two parasite, they reclassified Laverania malariae into Haemamoeba and renamed it H. malariae. In 1891, Grassi performed the first inoculation of malaria parasites from one bird into another. Grassi reused the genus Laverania for O. malariae (unbeknown to Laveran, Oscillaria was already a scientific name for other protists). (The full report was published in September 1898.) In Ross's case the experiment was an infection of bird malaria in sparrows from the bite of what he called "grey" mosquitos. Upon the news, Grassi knew that it was important to test the possibility of human infection from mosquitos. In September, on his way back to Rome, he collected mosquitos some of which he could identify as Anopheles. When the blood fed mosquitos were dissected after few days, several developmental stages of the parasite were visible inside the mosquito. The most important observation was oocysts (from which human infective forms, sporozoa, would eventually emerge) that indicated the successful growth of the parasite in the mosquitos. Grassi, Bignami and Bastianelli reported the discovery to the Accademia dei Lincei on 6 November 1898, and was formally read before the meeting of the academy on 4 December. Bignami and Bastianelli published the experiments in the December issue of the Lancet, Bastianelli especially trying to take majority of the credits in a single authored report, and explicitly omitting the contributions of Grassi. Grassi published a justification that the main critical experiment was designed and performed by only himself.

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. The enigma was solved in 1925, soon after his death, by his pupil Falleroni, who demonstrated that there are six cryptic species, of which only four bite humans and transmit malaria. It was useful but not a great success, as the drug could not prevent the infection. Grassi was among the scientists who advocated the need to eradicate the vector mosquitos to put an end to continued transmission of the parasite. In 1918, he established what he called "malaria observatory" at Fiumicino where he could monitor the extent of mosquitos migrating and biting humans in the residential areas. At the time, those who advocated the mosquito eradication method believed that it would be sufficient to control the insect breeding places within the human habitations, such as the marsh area in case of Fiumicino. 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). 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.

Grassi authored more than 250 scientific papers and, in collaboration with his students and colleagues, wrote another 100. 1898. Rapporti tra la malaria e peculiari insetti (zanzaroni e zanzare palustri). R. C. Accad. Lincei 7:163–177. 1899. Ancora sulla malaria. R. C. Accad. Lincei 8:559–561. with Bignami, A. and Bastianelli, G 1899. Resoconto degli studi fatti sulla malaria durante il mese di gennaio. R. C. Accad. Lincei. 8:100–104. 1901. Studii di uno Zoologo sulla Malaria. Atti dei. Linncei. Mem. Cl. sc. fis. ecc.3(5), No. 91:299–516.6 plates in colour.