![\"\"](\"http:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2018\/07\/092_Memoria07_265.jpg\")
Doctrine Microbienne <\/span><\/a> Illustration of a glass flask used to produce the vaccine, published in a book in 1885Doctrine Microbienne <\/span><\/p><\/div>\n A month earlier, the Minister of Empire Affairs, Pedro Le\u00e3o Veloso (1828\u20131902), had promised Freire an \u201canswerable reward\u201d if he succeeded in his work. In April the doctor began reporting on his experiments in the Gazeta de Not\u00edcias<\/em>, in which he also responded to doctors and columnists who challenged or ridiculed his work.<\/p>\n \u201cScience was not yet confined to scientific journals and the academic domain,\u201d says historian of science Jaime Larry Benchimol, a researcher at Oswaldo Cruz Foundation\u2019s Casa de Oswaldo Cruz (COC-FIOCRUZ), who described the morgue scene in his book O desenvolvimento da vacina contra a febre amarela<\/em> (The development of a yellow fever vaccine; Editora Fiocruz, 1999) and has written several other articles about Freire. \u201cScientific debate was a public matter, and rhetoric an indissoluble part of doing science at that time.\u201d<\/p>\n Album, Year 1, No. 22. 1893<\/span><\/a> Freire gained prestige and was invited to Paris and Washington, D.C., to speak about his workAlbum, Year 1, No. 22. 1893<\/span><\/p><\/div>\n A few months later, in August 1883, Freire presented to the new Minister of the Empire, Francisco Antunes Maciel (1844\u20131917), the results of his experiments with attenuated cultures of his yellow fever microbe. Maciel appointed a commission from the Central Board of Public Hygiene to scrutinize the work done at the school of medicine. Clashes with the minister over problems that had occurred in a smallpox vaccination operation in Bahia led the committee to resign, and in October Freire was appointed chairman of the Board.<\/p>\n The physician had already begun inoculating volunteers with his vaccine, under protest from the now defunct committee. He claimed he had received authorization from the government, although, as recounted in Benchimol’s book, the then chairman of the Imperial Academy of Medicine, Nuno de Andrade (1858\u20131915), remarked at the time that \u201cDr. Freire\u2019s authorization to inoculate volunteers was given by Dr. Freire himself.\u201d By November 1, 48 people had been vaccinated, mostly Spanish and Italian immigrants newly arriving in Rio. In November the Ministry of the Empire authorized the publication of advertisements inviting immigrants and natives to submit to vaccination at Instituto Vac\u00ednico, where the smallpox vaccine was being administered. Around 13,000 people are believed to have been injected with Freire\u2019s vaccine between 1883 and 1889 in the then federal capital and across the states of Rio, S\u00e3o Paulo, and Minas Gerais.<\/p>\n \u201cThere were then a number of competing theories, including miasma theory [that diseases result from the foul odors of decaying organic matter and still water], the proposed solution to which was urban reform in Rio,\u201d Benchimol says. \u201cYellow fever was highly problematic, with the same 40% mortality rate as today.\u201d The battle for priority in the discovery of the disease-causing agent raged on until in 1928 the yellow fever microbe was determined to be a virus that had been isolated from naturally infected monkeys in West Africa. In 1883 a physiologist from the National Museum, Jo\u00e3o Batista Lacerda (1846\u20131915), presented to the Imperial Academy of Medicine what he claimed to be the true cause of yellow fever: Fungus febris flavae<\/em>, which accumulated in the liver and caused severe jaundice. Lacerda lost credibility after a French bacteriologist examined his material and determined it was a bacterium, not a fungus. Two other yellow fever agents were described in an edition of Annales de l\u2019Institut Pasteur<\/em> in 1897: the first was a bacterium thought to dwell in patients’ digestive tract, which had been identified by a physician in Rio, Wolf Havelburg; the second was Bacillus icteroides<\/em>, identified by Italian bacteriologist Giuseppe Sanarelli (1864\u20131940), director of the Institute of Experimental Hygiene at the University of Montevideo, Uruguay.<\/p>\n Fundo Instituto Oswaldo Cruz <\/span><\/a> Embryonated eggs being prepared for the production of yellow fever vaccine in Rio in 1943Fundo Instituto Oswaldo Cruz <\/span><\/p><\/div>\n New discoveries<\/strong> \u201cFresh discoveries and new scientific procedures ultimately invalidated Freire’s and others’ work in the late nineteenth century,\u201d says historian of science Marta de Almeida, a researcher at the Museum of Astronomy and Related Sciences (MAST). In 1881, at a scientific conference in Washington, D.C., the Cuban physician Carlos Finlay (1833\u20131915) presented his theory that the agent of yellow fever was transmitted by the mosquito Stegomyia fasciata<\/em>, which would later be renamed Aedes aegypti<\/em>. \u201cFinlay also assumed that the yellow fever agent was a bacterium, Micrococcus tegraenus<\/em>, which helps explain why his theory took long to be accepted,\u201d says Benchimol. It was only in 1900 that the United States Army, which had also been searching for a bacterium as the cause of yellow fever, tested Finlay’s mosquito-vector hypothesis by implementing mosquito control in Cuba, and within six months the disease that had plagued US soldiers had vanished. Physician Em\u00edlio Ribas (1862\u20131925), director of the Sanitary Service of the State of S\u00e3o Paulo, confirmed \u200b\u200bFinlay’s transmission theory in 1898 when he acquired a mild form of the disease after letting himself be bitten by infected insects (see<\/em> Pesquisa FAPESP,<\/em> issue no. 157<\/em><\/a>). In Rio, physician Oswaldo Cruz (1872\u20131917) led programs to eradicate the mosquito vector. \u201cAt first doctors shunned the idea that yellow fever was transmitted by mosquitoes, which were seen as a nuisance, but a perfectly harmless one,\u201d says Almeida.<\/p>\n<\/a>\u201cTo demonstrate that his vaccine was effective, Freire produced annual reports\u2014albeit using very shoddy statistical methods\u2014showing the number of people he had vaccinated and the lives he had purportedly saved,\u201d says Benchimol. As part of his argument, in 1885 the physician published a 451-page book, Doctrine microbienne de la fi\u00e8vre jaune et ses inoculations pr\u00e9ventives<\/em>, with photos of the yellow fever agent and descriptions of his method and of vaccinated individuals. The prominence and prestige he had gained from his achievements was such that he was invited to speak about his work in Paris and Washington, D.C.<\/p>\n
\nIn 1887, the American bacteriologist George Sternberg (1838\u20131915) criticized the inconsistent working methods and the vaccines created by physician Manuel Carmona y Valle (1831\u20131902) in Mexico, and by Freire in Brazil, after visiting their laboratories on commission by the United States Government. \u201cSternberg was convinced that the failure of his own attempts to isolate the \u2018yellow fever germ\u2019 was sufficient proof that others’ success could only be illusory. He asserted that Freire’s and Carmona y Valle’s methods had no scientific value,\u201d wrote historian of science Ilana L\u00f6wy, a researcher at the Center for Research in Medicine, Science, Health, and Society (CERMES) in Paris, in her book V\u00edrus, mosquitos e modernidade: A febre amarela no Brasil entre ci\u00eancia e pol\u00edtica<\/em> (Viruses, mosquitoes and modernity: Yellow fever in Brazil between science and politics; Editora Fiocruz, 2006).<\/p>\n