Science and the Belle Époque in the Federal Capital in the early twentieth century
Dominichi Miranda de Sá
Casa de Oswaldo Cruz/Fiocruz
“Times have changed. (…) Brazil’s soul and brain take on modern features, ideas of the world are now absorbed with a speed that would amaze our grandparents.”
João do Rio, The Literary Moment
In the early years of the twentieth century, Rio de Janeiro was the great intellectual center of Brazil. It hosted the Municipal Theater, the National Library, the School of Fine Arts, and Central Avenue with its cafes, bookstores, cinematographers, and patisseries. All these venues were meeting places for men of science, men of letters, journalists, artists, literati, chroniclers, bachelors, poets, publicists, reclaimers, writers, lecturers, academics, philologists, novelists, speakers, polemists, and prosers, in short, the ‘intellectuals’. Despite their official occupations as civil servants, politicians, lawyers, teachers, military, engineers, or doctors, they were devoted to cultural creation, social change, and the interpretation of the country’s political moment.
At this time, the city was undergoing intense urban modernization characterized by the appearance of new buildings such as the Municipal Market, the Quinze Square embankment, Mauá Square, Mangue Avenue and Central Avenue itself, later called Rio Branco Avenue, and by the adoption of ‘progress’ and ‘civilization’ symbols such as automobiles, electric trams, advertising placards, telegraphy, telephones, typewriters and gramophones. These modern artifacts competed with reading as a form of leisure and learning, shortened distances, and created a new perception of time as ‘speed’, ‘hurry’ and ‘thirst for novelty’.
Although the city has undergone constant remodeling since the arrival of the Portuguese royal family in 1808 – such as sidewalks, lighting, construction of the Mangrove Channel and expansion of the urban core to São Cristóvão, Catumbi, Rio Comprido, Tijuca, Laranjeiras, Catete, Botafogo and Gávea by trams, and to Engenho de Dentro, Piedade, Sampaio, Quintino, Meier, Mangueira, Mangueira, Encantado and Madureira by rail only with the change of the political regime in 1889 (which made it a federal capital) and the reforms carried out under Mayor Francisco Pereira Passos‘ command (1902-1906) characterized the beginning of the so-called Belle Époque in Rio de Janeiro. The urban beautification, flanked by sanitation and fighting yellow fever and smallpox, created a general sense of superiority and triumph over the symbols of Portuguese colonial tradition; A sensation that can be summed up by one of the great mottos of the period created by journalist Figueiredo Pimentel for his column The Binoculars: “Rio civilises”.
Innovations also occurred in the press, the most important vehicle of cultural production in the period, for providing the best bonuses and intellectual positions. Typographies that published newspapers and magazines underwent considerable technological improvement in those early years of the twentieth century, which made possible to increase the number of journals and some graphic innovations such as color pages and the use of photographs, and the introduction of new genres of writing, like reportage, interviews, surveys, advertising and chronicles.
Literary conferences on various subjects were held at the National Institute of Music, the Casino and the Municipal Theater, as well as in the halls of the city’s great ladies and wealthy couples. The saloons of Araújo Vianna, Azeredo, Sampaio Araújo, Laurinda Santos Lobo and the soirées promoted by Coelho Neto, Inglês de Souza, Olavo Bilac, Medeiros and Albuquerque, João do Rio, Alcindo Guanabara, Julia Lopes and Souza Bandeira were prestigious. They were part of the city’s mundane life, as were the official banquets, the battle of the flowers, the receptions, the theater seasons, the pic-nics, the five-o’clock-tea, the squares, the gardens, the fine shops, the balls, tea balls, open-air concerts, regattas, racing, nightclubs, gambling and music halls, turfs, foot-ball and choirs.
In the Federal Capital were also concentrated the most important literary societies, medical journals, medical-surgical schools, scientific associations and institutions of higher education of the country, as, for example, the Institute of Manguinhos (what was then called the Institute Oswaldo Cruz), the Faculty of Medicine, the Botanical Garden, the Astronomical Observatory, the Polytechnic School, the Brazilian Historical and Geographic Institute, the National Academy of Medicine, the Brazilian Academy of Letters, the Geography Society and the National Museum.
Considered the main agent of the process of modernization and civilization of the country, ‘science’ was also one of the most important and current affairs of the daily and weekly newspapers circulating in Rio de Janeiro of the period. Scientific themes featured in their front page calls, articles, editorials, sections and special issues. The press reported on new scientific discoveries, scientists’ travel abroad, the presence of foreign scientists in the country, their biographies, profiles and obituaries, and also the conduction of interviews and reproduction of the lectures, classes and speeches given at the most prestigious institutions of the period. At that time, it was believed, social development would only be possible through the widespread diffusion of science, with all its desirable moral, civilizing, physical, economic and political implications.
The spirit of ‘modernization’ and ‘civilization’ that changed the city’s landscape also led its intellectuals to create new institutions such as the Brazilian Academy of Sciences (1916), the University of Rio de Janeiro (1920) and the Brazilian Association of Education (1924) among others. They all represented new professional interests and new educational ideals.
Among these new professional interests, the professionalization of experimental research in the country should be highlighted. The Brazilian men of science as they were then called were those who graduated and worked in medical schools, natural history museums, scientific societies, historical and geographical institutes, medical journals, medical schools, agricultural and scientific institutes, in scientific committees and expeditions, discussed systematically, in the early years of the twentieth century, the importance of the realization of “pure science” in Brazil.
In other words, they wanted the creation of universities for the training of specialized professionals who could dedicate themselves to studies and experiments, with freedom and time available to research, read, participate in national and international congresses. It is worth remembering that, until the 1920s, there were no universities in Brazil and there were only few institutions, except those mentioned above, in which men of science could professionalize and develop their research with exclusive dedication.
All these debates between 1910 and 1920 do not mean that Brazilian science was incipient or of poor quality. Brazilians participated in controversies and international congresses writing important works and also making innovative scientific discoveries. What they reinforce in the defense of “pure science” was the improvement of the institutional conditions necessary for, as they said, the “impartial search for the truth”. And, according to them, this commitment could only be honored with the professionalization of research and scientific studies and the specialization of their intellectual formation. Thus, in 1916, the Brazilian Society of Sciences was created, transformed in 1921 into the Brazilian Academy of Sciences (ABC). Among its members were Oswaldo Cruz, Carlos Chagas, Alberto Betim Paes Leme, Henrique Morize, Alberto Childe, Edgard Roquette-Pinto, Alipio Miranda Ribeiro, Everardo Backheuser, Arthur Moses, Juliano Moreira, Bruno Lobo, Euzébio de Oliveira, Licínio Cardoso and Amoroso Costa. In addition to promoting its dedication to scientific research, the ABC included the organization of science courses and conferences, the creation of universities in the country, the publication of a journal and the establishment of awards and rewards for original works. And universities, in which the “research of new problems and unresolved national issues” would be carried out (Revista Ciência e Educação, 1929), would associate more specifically, according to the Association’s members, with the promotion of Brazil’s progress, since, according to themselves, Brazilian scientists would be responsible for assessing and directing the country’s social, political, economic and cultural life.
These ideals of intellectual specialization and professionalization of experimental research have established an agenda of debates and institutional achievements that have been consolidated with the participation, the initiative or the ideas of this generation of Brazilian scientists who created the Brazilian Academy of Sciences, the University of Rio de Janeiro in 1920, the Brazilian Association of Education in 1924, the National Institute of Weights and Standards in 1930, the Manifesto of Pioneers of New Education in 1932, the University of the Federal District in 1935, the Brazilian Society for the Progress of Science in 1948 and the National Council of Science and Technology in 1951.
Oswaldo Cruz and the Manguinhos Institute
Jaime L. Benchimol
Casa de Oswaldo Cruz/Fiocruz
Born on August 5, 1872, in São Luís do Paraitinga, interior of São Paulo, Oswaldo Cruz received a doctorate from the Rio de Janeiro Medical School in 1892 with a thesis on Microbial transmission by water. In 1896, he traveled to France to a specializaton at the Pasteur Institute, when the possibilities of both vaccines and healing serums seemed limitless, newly developed technology for tetanus and diphtheria by Emil von Bhering, Shibasaburo Kitasato, and Emile Roux. In the same year that Oswaldo Cruz returned to Rio de Janeiro (1899), the bubonic plague arrived in Brazil. In the wake of this pandemic followed the Pasteurians, achieving sensational victories. In 1894 Alexander Yersin (1863-1943) was able to identify the plague bacillus in Hong Kong and before the end of the year developed serum against the disease with Albert Calmette (1863-1933) and Amédée Borrel (1867-1936). In 1898 Paul-Louis Simond confirmed in India the hypothesis that it was fleas that transmitted rat to rat disease and rat to man. In Indian prisons and barracks Haffkine experimented an anti-plague vaccine. In the city of Porto (Portugal), in 1899, Calmette and Salimbeni improved the technique of whey preparation, when the plague migrated from there to Brazil in steamboats full of immigrants.
The difficulty in obtaining serum and vaccine led the São Paulo government to promote the creation of a laboratory to manufacture them at Fazenda Butantã. It began operations at the end of 1900, under the direction of Vital Brazil, soon after the serotherapic laboratory was created in Rio de Janeiro, on the Manguinhos farm, under the technical direction Oswaldo Cruz. On October 30, 1900, the General Direction of Public Health received the first hundred vials of anti-plague vaccine, assuming Cruz the exclusive direction of the Federal Sorotherapic Institute.
As soon as he was elected president of the Republic, on November 15, 1902, Francisco de Paula Rodrigues Alves issued a Manifesto to the nation that qualified the sanitation of Rio de Janeiro, then the Brazilian capital, as his most serious concern. During his tenure as president of Sao Paulo (1900-1902), São Paulo’s public health in that state embraced the theory of the Cuban Carlos Finlay that yellow fever was transmitted by mosquitoes and not by contaminated objects or miasmas. To carry out the urban reform for decades advocated by hygienists for Rio de Janeiro, Rodrigues Alves chose a team of first-rate engineers. Rodrigues Alves appointed mayor of the city, Francisco Pereira Passos, had seen the reform carried out in Paris by Georges Eugène Haussmann (1853-1870) under Napoleon III. From the rubble of the popular neighborhoods he saw the outlines of the new metropolis that would serve as a model for similar urban renovations around the world, including Rio de Janeiro.
Oswaldo Cruz took over the General Direction of Public Health (DGSP) with the mission of facing three diseases: yellow fever, smallpox and bubonic plague. In April 1903, he presented the plan of the campaign against the first disease transmitter, Stegomyia fasciata (present-day Aedes aegypti): to prevent mosquito contamination by yellow fever victims, to prevent the infection of receptive persons by contaminated mosquitoes, and the maintenance of sporadic cases that ensured the continuity of the disease during epidemic intervals. Bubonic plague would be stopped by the extermination of mice and the use of serum and vaccine manufactured in Manguinhos. As for smallpox, vaccinating the population would suffice.
When the bill was submitted to Congress reinstating the compulsory vaccination and revaccination against smallpox, opposition to “General Mosquito Swatters” (Oswaldo Cruz) and “Pull-Down” (“Bota-Abaixo”) (Pereira Passos) intensified. When the newspapers published, on November 9 of the same year, the draft of the decree regulating that “Code of Torture”, the city was convulsed for over a week by the Vaccine Uprising (Revolta da Vacina). The population paid twice as much for it: in addition to fierce repression, it had to endure, in 1908, the deadliest smallpox epidemic known to Rio de Janeiro, in which nearly 6,400 people died.
In assuming the direction of Public Health, Oswaldo Cruz proposed to the Congress that the Federal Serum Therapy Institute be transformed “into an Institute for the study of tropical infectious diseases, according to the lines of the Pasteur Institute of Paris”. The proposal was overturned, but that did not prevent him from giving Manguinhos the technical and material conditions to quickly surpass his original design.
The early team was restricted to the principal, two heads of service, and two student assistants. The institute was sought by doctoral students who did not find in the Faculty of Medicine the right conditions to develop work on microorganisms and their hosts.
In Manguinhos there was no separation between research, teaching and manufacturing of biological products. In 1906, for example, Figueiredo de Vasconcelos along with Ezequiel Dias took care of the preparation of the serum and the plague vaccine. He prepared the bacterium Burkholderia mallei and studied the glanders and the transmission of chicken spirilose by bedbugs. Henrique da Rocha Lima was investigating the pathological anatomy of yellow fever. Cardoso Fontes was responsible for the conservation of microbial cultures and the preparation of tuberculins. Henrique Aragão diagnosed the plague, prepared anti-streptococcal serum, studied equine piroplasmosis, and dedicated himself to the systematic classification of a family of ticks, the ixodids. Arthur Neiva did mosquito systematics and Carlos Chagas studied the life and habits of malaria transmitters, a disease that had been the subject of his doctoral thesis. Alcides Godoy prepared antidifteric and tetanus serums and dosed antipestos. With the help of his colleagues, including Chagas, he would soon develop the vaccine against symptomatic anthrax, or plague, an epizootics that wiped out 40 to 80 percent of calves in several Brazilian states. Other veterinary products would be developed later.
The working environment in this place away from the urban area differed from the bellicose ambience in which the demolitions and health campaigns took place. Researchers needed to meet public health demands, but were free to choose their research objects. Oswaldo Cruz wanted the members of his “kindergarten of science” – his expression being everyone under 30, to gain confidence in themselves to develop their own original work.
The boundaries of the Institute expanded into three distinct planes. Manufacturing of biological products, research and teaching – aspects peculiar to the Pasteur Institute of Paris – still define the profile of the large conglomerate that is the Oswaldo Cruz Foundation. Human diseases, animals and, to a lesser extent, plants, concentrated investigation that put the institution in contact with different “clients” and research communities, reinforcing its social support bases. The dilation of borders also had geopolitical connotations, as for the European institutes that acted in the African and Asian colonial possessions. More and more often, scientists from Manguinhos would plunge into the backlands of Brazil to study and fight diseases, especially malaria.
In 1905, Carlos Chagas executed the first antimalarial campaign in Itatinga, São Paulo, where a hydroelectric dam was built. In 1906, Chagas and Arthur Neiva fought malaria in the Baixada Fluminense, and that same year, Chagas went, with Belisário Pena, to the north of Minas Gerais, where the disease prevented the extension of the Central Railroad of Brazil. In 1908, Neiva would act in other regions.
By putting their expertise at the service of railroads, hydroelectric plants, agribusiness or extractives, they would face different problems from those experienced in urban centers. They would have the opportunity to study little or unknown pathologies, and to collect biological materials that would extend the Institute’s biological collections and the horizons of tropical medicine in Brazil.
Despite Oswaldo Cruz’s prestige, Manguinhos was in a rather fragile position because he had, without legal support, extravasated the original framework of the Sorotherapic Institute. Its transformation into an Institute of Experimental Medicine was again requested from Congress in June 1906 (the year in which the first branch was inaugurated in Belo Horizonte, the newly founded capital of Minas Gerais). To a large extent, the battle was won in a theater far from the Brazilian capital. The Board and the Institute headed by Oswaldo Cruz were the only South American institutions to attend the 14th International Congress on Hygiene and Demography, and the attached Hygiene Exhibition in Berlin in September 1907. The gold medal won there had huge repercussions.
Still in Paris, Oswaldo Cruz wrote the rules of the Institute of Experimental Pathology, created in December 1907, and renamed the Oswaldo Cruz Institute in March 1908.
At the end of this year, by conducting the campaign against malaria in northern Minas Gerais, Chagas made the discovery that would be celebrated as one of the “Glories of Manguinhos”: he identified a new vector (the blood-eating insect known as “barber”), a new protozoan species (named Trypanosoma cruzi) and a new disease that would bear its name. The discovery would consolidate protozoology as one of the Oswaldo Cruz Institute’s most important research areas and would design it internationally.
Between 1909 and 1910, members of the Institute did further studies in Europe and the United States. In July 1908, two teachers at the Hamburg School of Tropical Medicine went the other way. Stanislas von Prowazek, Schaudinn’s successor, and G. Giemsa, inventor of the most commonly used hematozoan staining method, were hired for six months to give courses and publish the results of their research firsthand in Memórias do Instituto Oswaldo Cruz, recently opened. In May of the following year came Max Hartmann of the Berlin Institute for Infectious Diseases. Giemsa was back in Manguinhos in 1912, as was Hermann Duerck, professor of pathological anatomy at the University of Yena.
New Brazilian researchers joined the Oswaldo Cruz Institute during this period. The main acquisition was Adolpho Lutz, who left the Bacteriological Institute of São Paulo in 1908. It would give great impetus to medical zoology, botany and mycology and would publish key works on the life cycle of Schistosoma mansoni.
In November 1909, Oswaldo Cruz left the Public Health leadership at a tumultuous juncture due to the death of President Afonso Pena, the interim of Vice President Nilo Peçanha and the polarized presidential campaign between “civilist” Rui Barbosa and Marshal Hermes da Fonseca. Although he was a national idol, Oswaldo Cruz had failed to achieve any of the goals proposed for his second term as Director General of Public Health. The campaign against tuberculosis had waned for lack of resources and political support; regulation of the compulsory vaccine law continued to be delayed. The state oligarchies blocked health actions in their territories, although yellow fever raged in northern and northeastern Brazil, jeopardizing what had been done in Rio de Janeiro.
At the margin of the government, then, the health scientists from Manguinhos would carry out their most spectacular actions in the interior, financed by private contracts, including with the state itself. In 1910 Oswaldo Cruz himself undertook two missions. The first for a bold venture in the Amazon jungle, the Madeira-Mamoré Railroad, known as the “devil’s railroad” for the fame it had to consume the life of a worker for every railway sleeper fixed. In October, he landed in Belém to run the campaign against yellow fever there.
Oswaldo Cruz intended to send researchers and “mobile hospital busses” to various regions of the country to inventory their pathologies, especially Chagas disease. He even built a hospital in Manguinhos to study the most interesting cases collected in the interior of Brazil (Figure 1). Circumstances favored his plan. English-planted rubber plantations in Asia were about to supplant the Brazilian extractive industry. In January 1912, Congress belatedly approved the Rubber Defense Plan in order to modernize not only the extraction and processing of the product, but also the labor process, through measures that reduced “the absurdly high mortality rate.” From October 1912 to March 1913, Carlos Chagas, Pacheco Leão, Joao Pedro de Albuquerque, and a photographer travelled much of the Amazonian river framework aboard a small steamboat equipped with what was needed for the studies they intended to do. At the same time, other expeditions from the Oswaldo Cruz Institute travelled through the Center and Northeast of Brazil, in the service of the Inspection of Works against Droughts, an organ created in 1909.
The Amazon rubber debacle was irreversible, and the old Republic of the colonels did not face the secular tragedy of the northeastern droughts. In this sense, the medical and health commissions were unhelpful. But the Oswaldo Cruz Institute laboratories provided a valuable set of materials concerning Brazilian pathologies. The reports written by scientists, rich in photographs and sociological and anthropological observations, constitute the first modern inventory of the living conditions of rural populations in Brazil. It had great repercussions with the intellectuals of the coastal cities, providing the debate on the national issue, which was beginning to be resized in terms of the dualist view, of long persistence in Brazilian social thought. The ufanist exaltation of Brazil’s “civilization”, inflated after the urban remodeling of Rio de Janeiro, collapsed with the corrosive revelations about that miserable and diseased “other” Brazil, plagued by endemics, including the trypanosomiasis discovered by Chagas (Figure 2)
Medical Theories: “Pasteurian Revolution” and Tropical Medicine from the 19th to the 20th Century
Jaime L. Benchimol
Casa de Oswaldo Cruz/Fiocruz
The creation of the Manguinhos Sorotherapic Institute (1899) and the discovery of Chagas disease (link to another text: “Discovery”) (1909) lead us to two interlinked ‘revolutions’ within laboratories and other domains of social life, such as clinical and hospital medicine, public health, and countless economic activities and everyday practices that were modified by the effects of microbes, insects, and other parasites and hosts, now recognized as hardly preventable ‘parts’ of men’s relations with one another and with one another. the nature.
In a schematic way, we can relate the first revolution to discoveries that incriminated increasing numbers of microorganisms as causing infectious diseases, and which led to the development of techniques to obtain vaccines capable of immunizing people and animals against them, and serums capable of healing individuals already affected by these diseases. The second revolution is closely related to the first: it has to do with the discovery that insects and other invertebrates could host pathogenic microorganisms to humans, animals and plants, thus explaining the mechanisms of disease transmission that for a long time they had remained enigmatic.
“Pasteurian revolution” is the term often used to refer to that of microbes, vaccines, and serums. It brings to the foreground France and the fundamental work of Louis Pasteur (1822-1895), his disciples and successors, but leaves in shadow the equally important contribution of other characters and countries, in particular Robert Koch (1843-1910) and other researchers from Germany. One aspect of the pasteurian revolution is precisely the enduring rivalry between the French and Germans, exacerbated during the Franco-Prussian War (1870-1) and the twentieth-century world wars.
The authors who wrote on the subject characterize in different ways the origins of this revolution. One approach starts from chemistry and controversy about the fermentation and putrefaction processes that permeated various life sciences, not to mention agro-industrial activities related to food and beverages. Such processes are a good guideline because infectious diseases were supposed at the time to be caused by miasmas, that is, gases from dirt and organic matter that rotted in the soil of cities and the soggy coastal plains. In the first half of the nineteenth century, the Swedish Jöns Jakob Berzelius (1779-1848) and the German chemists Friedrich Wöhler (1800-82) and Justus von Liebig (1803-73) were the most renowned representatives of the then hegemonic current which he attributed. these processes to the interaction only of chemical and physical forces. Liebig, for example, viewed fermentation and decay as chemical instability caused by the presence of an organic matter in the process of decomposition, in a state of internal molecular vibration that could be communicated to other materials, causing them to disintegrate as well. The French Cagniard de Latour (1777-1859) and Theodor Schwann (1810-82), and the German Friedrich Traugott Kutzing (1807-93) stood out in the opposing stream that historiography led to Pasteur. In concomitant and independent works published in the 1830s, they sought to demonstrate that the fermentation of beer and wine was the result of the activity of living cells or corpuscles that they classified as fungi or algae.
Pasteur approached the complex problem of fermentation from a discovery that restructured the perception of two strands of chemistry, organic and inorganic. In 1848, he demonstrated that racemic acid could be separated into two chemically identical (tartaric acid) but physically unequal components. Such molecular inequality or asymmetry was revealed by the way they behaved under a polarized beam of light: only one of the isomers deflected it. The relationship between this structural particularity and plant or animal life led Pasteur to migrate from this first object of study, which combined crystallography, chemistry and optics, to the controversial territory of fermentation, beginning with amyl alcohol, which had that intriguing property of diverting the plane of light polarization.
In 1857, Pasteur presented his first communication on lactic fermentation to the Lille Society of Sciences, Agriculture and Arts. In 1861, he turned to butyric and acetic fermentation, publishing five years later Studies on Wine, in which he correlated the diseases that afflicted industrialists and winemakers with the invasion of microorganisms that altered drink properties. Fermentation studies were discontinued during the period in which he considered the diseases caused to the silkworm (1865-1871). In 1876, he published Studies on Beer, which contained a more mature view of fermentation processes, with observations and concepts fundamental to the constitution of bacteriology as a discipline capable of explaining, in a new light, the origin and development of human disease. In these studies, Pasteur revealed a world populated by microscopic beings capable of surviving at the expense of mineral matter, with or without oxygen, using the simplest forms of carbonic compounds such as alcohol, acetic acid or sugar, and ammonia as a source of nitrogen. Each type of fermentation was related to the life of a specific microorganism that multiplied with incredible speed.
Between 1877 and 1887, aged 55-65, Pasteur led microbiology into medicine by discovering septic vibrium, the staphylococci responsible for boils and osteomyelitis, the streptococcus that caused puerperal infection, pneumococcus. During this period, due to pioneers such as Joseph Lister (1827-1912), asepsis and antisepsis began to become mandatory procedures not only in surgery but also in laboratories.
Then Pasteur’s studies on vaccines began. Except for the smallpox immunization technique proposed by Edward Jenner in the late eighteenth century, there was no other biological product of this nature for humans. Pasteur discovered the chicken cholera vaccine in 1880, and the following year made a spectacular demonstration of its effectiveness against anthrax. Then, at an International Medical Congress held in London, he defended a new concept of vaccine: immunization by inoculating artificially attenuated virulence microbial cultures in the laboratory. The passage to human pathologies, passing through the pig cholera vaccine (1883), was a technically, ethically and socially complex process that culminated in the application of the rabies vaccine to the Alsatian boy Joseph Meister in 6 July 1885.
In March of the following year, the Paris Academy of Sciences opened an international subscription for an establishment for that vaccine. D. Pedro II, the Brazilian monarch, was one of the first to contribute, and with such expressive sum that they honored him with a bust in the lobby of the Pasteur Institute, inaugurated in the French capital in November 1888. With a repertoire of activities that went beyond rabies prophylaxis, it would be the matrix or model of similar institutions around the world.
The Pasteur Institute of Rio de Janeiro was inaugurated, even shortly before the Parisian, but was restricted to the treatment of hydrophobia.
At that time, several Brazilian doctors had already turned to the investigation of pathogens, especially the cause of yellow fever, one of the most serious health problems in Brazil. Great stir caused, for example, Dr. Domingos José Freire (1843-1899), professor of organic chemistry at the Faculty of Medicine of Rio de Janeiro, who related the disease to a microscopic alga called Cryptococcus xanthogenicus, by analogy with the anthrax bacteria, whose Koch spores had recently discovered in the graves of animals victimized by the disease. Throughout the 1880s and 1890s, thousands of people in Rio de Janeiro and other cities in Brazil and even overseas underwent the vaccine that Freire developed with the alleged yellow fever microbe.
In those years, there was growing interest in the transmission mechanisms of diseases with a demonstrated or suspected microbial etiology. Pasteur and Lister’s emphasis on the ubiquity of airborne germs has receded from investigations into other vehicles or carriers: on the one hand, water, sewage, food, body droppings; on the other, dogs, cats, birds and insects. It was considered the mechanical transmission of the “viruses” (a term still used in its Latin sense, as a synonym for poison) caught in stagnant water, putrid matter and droppings, as flies did with the typhoid-causing bacillus. To a lesser extent, it was contemplated the spread of disease by blood-sucking animals, either directly by biting humans, or through the water contaminated by the infected insects that died in it, as Patrick Manson (1844-1922) supposed to occur with the Culex mosquito, which was found to be the transmitter of filaria.
In 1877-1878, this English physician unraveled almost the entire cycle of this worm, concatenating the parts of a puzzle that had begun to be deciphered in Brazil in 1866, when Otto Edward Henry Wucherer (1820-1873) attributed the so-called elephantiasis (filariasis) to a microscopic nematode (Wuchereria bancrofti) found in patients’ urine.
Manson’s work opened the door to other discoveries involving arthropods as intermediate hosts of pathogenic microorganisms for humans and animals. In 1893, Theobald Smith (1859-1934) and Fred Lucius Kilborne (1858-1936) uncovered the tick-borne transmission of the protozoan that caused the cattle fever disease called Texas fever. David Bruce described in 1895-1896 the mechanical transmission of trypanosomes by flies of the genus Glossina.
Malaria and yellow fever remained exposed to great uncertainty, in part due to the unsuccessful attempts to find their supposed microbial agents outside the human body. The hematozoan discovered in 1880 by Charles Louis Alphonse Laveran (1845-1922) – Oscillaria malariae, later called Plasmodium malariae – was found in the body of the sick, but could not be cultivated in vitro or experimentally produced.
From the mid-1890s, information and speculation about the role of insects in the transmission of diseases, especially flies, multiplied in the Brazilian and foreign press, facilitating their incorporation into the imaginary of urban populations as an omnipresent source of danger in the midst of replacing the impalpable miasmas. Doctors assumed they spread the microbes of carbuncle, Egyptian ophthalmia, Biskara bud, piã (bouba) and mormo. Alexander Yersin (1863-1943) found that dead flies in his laboratory contained the bubonic plague bacillus and could infect drinking water. E Joly (1898-1899) confirmed that they deposited on food and drink the tuberculosis bacillus discovered by Koch in 1882.
When Ronald Ross (1857-1932) unveiled, in 1898, the cycle of the bird malaria parasite in the Culex mosquito, and Giovanni Battista Grassi (1854-1925), Amico Bignami (1862-1919) and Giuseppe Bastinelli revealed the following year, the human malaria parasite cycle in Anopheles mosquitoes, the assumption that they played the same role in yellow fever became inevitable, the diagnosis of which fused with some of the fevers now interpreted as clinical signs of different species of Plasmodium .
Ross’s consecration as a British competitor to the French Pasteur and the German Koch was decisive for the realization of the project that Patrick Manson had defended in October 1897 at conferences at St. George’s Hospital: to invest in the training of physicians qualified to deal with, what he called, “tropical medicine”.
The expression is as problematic as the ‘pasteurian revolution’, and Manson was aware of it: the diseases found in the regions of the globe limited by these parallels also rage in temperate zones. Many Brazilian doctors would object to this concept that seemed to perpetuate the stigmas of unhealthiness and backwardness that originated in the eighteenth and nineteenth centuries, when medical theories that attributed infectious diseases to hot climates and their miasmas served to produce Eurocentric ideologies designed to legitimize the colonial expansion of European states. For Manson and his followers, climate and other environmental factors were relevant only to the extent that they influenced the living and reproductive conditions of pathogenic parasites and their hosts. The term “tropical medicine” came to be used to delimit a research territory that required doctors to have a different background from the faculties of medicine: knowledge of anatomy, physiology, clinic and therapy had to be combined with the tools of zoology and microbiology, so that doctors could understand and investigate the complex life cycles of worms and microbes and the vertebrate and invertebrate animals that hosted them.
In June 1899, the Liverpool School of Tropical Diseases started to operate; in October, the largest London School of Tropical Medicine was inaugurated. In June 1900, Drs. Walter Myers and Herbert. E. Durham, from the Liverspool school, headed to Brazil to investigate yellow fever. They hypothesized its transmission by a blood-sucking insect, already formulated in 1881 by the Cuban doctor Carlos Juan Finlay. It has gained greater consistency with the information provided to Myers and Durham by doctors linked to US troops who had just conquered Cuba from its former metropolis, Spain. If the Americans had not gone this way, perhaps Finlay’s theory would have been confirmed by the English in northern Brazil.
The conclusions of the commission headed by Dr. Walter Reed – demonstrating the mosquito’s role as a vector of yellow fever – were presented to the 3rd Pan American Congress in Havana in February 1901, at the same time that William Gorgas was launching in that city the campaign against the soon-to-be mosquito classified as Stegomya fasciata and later Aedes aegypti (the great dengue fever spreader today in Brazilian cities).
Then began the golden age of medical entomology. If at the previous conjuncture of the Pasteurian Revolution, carbuncle and then cholera and typhoid served as models for microbial hunters, now physicians dedicated to clinic and bacteriology, zoologists who had studied other groups of animals, veterinarians, botanists and even lay people fascinated by the study of nature reconfigured the network of actors that would collaborate or compete in the search for winged transmitters of malaria-like diseases and yellow fever.
One of the major problems they faced was a lack of knowledge about mosquitoes and other dipterans. Throughout the 19th century, only 42 species had been described within the Culicidae family established by Johann C. Fabricius in his Entomologica systematica (1794). In the first decade of the twentieth century alone there were more than two hundred new species, mostly by the English Frederick Vincent Theobald (1868-1930), the North American Daniel William Coquillett (1856-1911) and the Brazilian Adolpho Lutz (1855-1940), since 1893 director of the Bacteriological Institute of São Paulo.
Lutz’s first systematic observations concerned the mosquito as agent of the spread of yellow fever (1901). Although it was claimed, then, that Stegomyia fasciata was the sole transmitter of the disease, Lutz maintained that wild mosquitoes could also transmit the still unknown germ of the disease, a hypothesis that Fred L. Soper (1893-1977) and his staff at Rockefeller Foundation, would confirm, in Brazil, in 1932.
In 1903 Lutz published a fundamental study on forest-ridden malaria transmitted by mosquitoes that reproduced on water-bearing plants such as bromeliads. He had become the cluster of doctors in the country turning to this emerging research field, closely related to another, equally recent: the search in humans and other animals for protozoa, a group of unicellular microorganisms of great variety, in ways similar in which Plasmodium malaria agents had been described, which would soon cover the trypanosomes responsible for sleeping sickness and Chagas’ disease, among others.
Celestino Bourroul defended, in 1904, at the Faculty of Medicine of Bahia, the first thesis of Brazilian medical entomology (he would later become a professor of parasitology at the Faculty of Medicine of São Paulo); Lutz’s other interlocutor in studies on mosquitoes and protozoa was Francisco Fajardo, professor at the Rio de Janeiro School of Medicine, where he directed Carlos Chagas’ thesis on malaria, defended in 1903.
In 1901 came the contribution to the study of the culicidae of Rio de Janeiro, by the young Oswaldo Gonçalves Cruz, then technical director of the Federal Serotherapic Institute of Rio de Janeiro (Institute of Manguinhos). He had studied mosquitoes from some outbreaks of malaria on the outskirts of the capital – the far-off Botanical Garden, which the tram lines had just connected to the urban area; and Sarapuí, at the Baixada Fluminense, on the banks of the Central Railroad of Brazil. Excursions to these outbreaks of malaria were made with the technicians of Manguinhos. Henrique da Rocha Lima, who would join the institute in 1903. Also, Figueiredo de Vasconcellos, Antonio Cardoso Fontes, Ezequiel Dias and even the architect Luiz de Morais, hired to build the monumental buildings that would house the Oswaldo Cruz Institute.
One of the areas most invested in this inaugural phase of the Institute was entomology, under the responsibility of Oswaldo Cruz, Arthur Neiva and Carlos Chagas himself, devoting the last two intensely to the study of the life and habits of malaria transmitters.
The discovery of Trypanosoma cruzi and trypanosome studies in the early twentieth century
Magali Romero Sá
Casa de Oswaldo Cruz/Fiocruz
Animal parasitic trypanosomes have been known since 1841 through the work of Gustav Valentin, a professor at the University of Bern, who found them in trout. In 1843, David Gruby first described a trypanosome discovered in frog blood: the Trypanosoma sanguinis. However, it was not until the late nineteenth century that this group of protozoa was associated with diseases of domestic animals and later on of man. In 1880, Griffith Evans discovered Trypanosoma evansi, agent of a fatal disease that affected horses and camels known as “surra”. A few years later, between 1895 and 1896, David Bruce found that trypanosomes (Trypanosoma brucei) were agents of the disease known as nagana, a disease that affects equines and other animals. At the beginning of the twentieth century, Trypanosoma gambiense, which causes African trypanosomiasis or sleeping sickness, which affects the African population is discovered.
The first observations on trypanosomes made in Brazil were from Adolpho Lutz in the 1890s, when in his studies on hematozoa he observed the occurrence of these protozoa in rats and frogs. Years later, in 1907, Vital Brasil and A. Lutz recorded the occurrence of an epizootic trypanosomiasis in the states of Sao Paulo and Pará. The disease known as butt-break (“quebra-bundas”) or hindquarters disease (“mal-das-cadeiras”), affected mainly equines and was caused by a trypanosome discovered in 1901 by the then director of the Bacteriological Institute of Asuncion, Paraguay, Miguel Elmassian. In the same year, this species was named Trypanosoma equinum by O. Voges. The work of Lutz and Vital Brazil has contributed to extending the known geographical distribution of the disease – previously registered in Argentina, Uruguay, Paraguay and the Pantanal region – to southeastern Brazil and the Amazon region. Lutz further strengthened the hypothesis that capybara (Hydrochaeris hydrochaeris), the largest South American rodent, was the natural reservoir of the trypanosome and a possible diptera insect (fly) as its vector, similar to African trypanosomiasis.
Less than a year after the contributions of Lutz and Vital Brasil, three new forms of trypanosomes from Brazil are discovered: two in monkeys and a third, the cause of American trypanosomiasis or Chagas disease, which will boost subsequent protozoology studies in Latin America. and add a new human disease caused by protozoan to medical and scientific textbooks.
During his work on malaria control in the Lassance area of Minas Gerais, Carlos Chagas finds a new form of trypanosome by analyzing the blood of the marmoset Callithrix penicilata, describing it as Trypanosoma minasense in 1908 (the work was published in Brazil-Medico in 1908 and in 1909 at the Archiv fur Schiffs- and Tropenhygiene, Germany). Months before Chagas’ discovery, another South American monkey trypanosome had been discovered by Herbert von Berenberg-Gossler while searching for malaria parasites in the Amazonian monkey Brachyurus calvus, commonly known as “cacajao”. To this new species, Berenberg-Gossler named Trypanosoma prowazekii, in honor of Czech protozoologist Stanilas von Prowazek.
Still in Lassance, shortly after the discovery of the trypanosome in marmosets, Carlos Chagas had his attention turned to a hemipterous insect that hid during the day in the cracks of the muddy walls of local dwellings and only went out at night to feed. For bitinh the inhabitants in the face while sleeping, this hemipter was commonly known by the name of “barber”. Examining the insect, Chagas found “numerous flagellates with morphological characteristics of critidia” and inferred that they were intermediate forms of the trypanosomes previously discovered by him in the marmosets. To confirm his hypothesis, he sent the parasitized insects to Manguinhos to be used in experiments on monkeys of the same species, but free of parasites. The experiment, conducted by Oswaldo Cruz, resulted after 20 to 30 days in a large number of trypanosomes in the monkey’s peripheral blood, but with a completely different morphology from the trypanosome previously found by Chagas in the marmoset. Chagas even found that it was distinct from any previously known trypanosome species, which led him to describe it as a new species, which he named Trypanosoma cruzi after Oswaldo Cruz.
Chagas’s new discovery triggered a radical change in the history of tropical medicine in Brazil. Soon after the description of the new trypanosome, the species will be identified as a pathogen of a new human trypanosomiasis unknown to science until that time. In addition to identifying this new pathogen and a new disease, Chagas will also discover a new group of insect vectors, the hemiptera. A group composed mainly of phytophagous species, hemiptera have only one subfamily of hematophagous species (Triatominae), a very important subgroup for medical research. The vast majority of Triatominae are native to the Neotropical and Neartic regions. The geographical distribution of Triatominae extends from Salt Lake City in the United States (41º N) to the north to Patagonia in southern South America. The Chagas discovery has definitely demonstrated the importance of tritomines in vector insect studies, especially in the Americas.
At the time, Carlos Chagas’ new discoveries in the field of protozoology were being followed in Manguinhos by researchers at the Hamburg Institute of Maritime and Tropical Diseases, the protozoologist Stanilas von Prowazeck Edler von Lanow (1875-1915) and the German chemist and pharmacist Gustav Giemsa (1867-1948). The two researchers had arrived in Brazil on July 3, 1908, invited by Oswaldo Cruz to teach protozoology and chemistry courses respectively, and to collaborate with the researchers of the institution. Prowazek, a disciple of Fritz Schaudinn and his replacement at the Hamburg Institute, came to Manguinhos with extensive experience in the study of Protists, especially trypanosomes. In his luggage, he brought animals infected with different species of trypanosomes such as T. equiperdum, which caused the horse disease known as “durina”, T. gambiense, which caused the sleeping disease, and T. congolense, which mainly affected cattle, to be studied by the Manguinhos researchers.
Prowazek followed Chagas’s work closely, sending information to Hamburg about the new trypanosomes discovered and encouraging Chagas to submit his findings for publication in a German journal. On December 17, 1908, shortly after publication in Brazil-Medico, the new trypanosome species described by Chagas were sent to the Archiv fur Schiffs- and Tropenhygiene and were published in the first issue of 1909.
Chagas’s observations about the development of T. cruzi in the intermediate host left a deep impression on Prowazek, leading him, as soon as he returned to Hamburg in February 1909, to publish work entitled “Critical Observations on the Trypanosome Problem”. In it, Prowazek makes the following observations about Chagas’s work: “With regard to the development of trypanosomes in intermediate hosts, we can finally cite C. Chagas’s observations on Trypanosoma cruzi n. sp. (Archiv fur Schiffs-Tropenhygiene, volume XIII, no. 4), which is transmitted through a bed bug (Conorrhinus)”. Regarding the morphological changes of the parasite, we refer to the communication itself. Particularly important to me is the (following) observation: ‘In the Conorrhinus celeloma I found adult forms of parasites that differed from those of the intestinal canal by presenting characteristics of the adult trypanosome’. “These are the facts that, obtained in part on an experimental basis (Manteufel, Kleine, Baldrey and Chagas), speak in favor of an intermediate host trypanosome development.” Prowazek ends his work with the following comment:
“For pathogenic trypanosomes, development in an intermediate host is not yet definitively proven; yet, in recent times, evidence has accumulated in this direction and it is to be expected that the coming years will bring us the ultimate solution to this problem.”
The evidence Prowazek was referring to was published by German researcher Friedrich Kleine, who had been studying African trypanosomiasis (sleeping sickness) since his trip to Africa as a member of the First German East African Sleep Disease Commission in 1906- 7 In 1909, Kleine published the development of Trypanosoma gambiense, the agent of human African trypanosomiasis on the fly. To this end, he conducted experiments on the transmission of human patients to large and small apes, proving that the parasite had been present in glossine flies for a minimum period before causing infection. Kleine further showed that only the metacyclic forms in the insect’s salivary glands were infectious.
Soon after Kleine’s work, Chagas will identify at the same place (Lassance) where he found the infected bedbugs, a young girl infected with Trypanossoma cruzi and thus prove the pathogenicity of the protozoan he discovered in the insect. It will then finally describe the complete development of the pathogenic protozoan in the intermediate host – the barber – and the definitive host – the man. As Prowazek had predicted, evidence of pathogenic trypanosomes in intermediate hosts didn’t take long to happen.
The story of the discovery of Chagas disease differs completely from its African counterpart – sleeping sickness. The study of African trypanosomiasis was developed through simultaneous veterinary and human investigations in close harmony with the colonial expansion of European countries into African and Asian territories. The diseases that afflicted animals and people were gradually being identified and involved different actors at different times. During the process, English, French, Belgians and Germans swept their territories for parasites and vectors, with field research and in local or metropolitan laboratories. Both the new discoveries and the intense circulation of ideas among scientists were fundamental factors for the progressive advancement of the knowledge of trypanosomes and trypanosomiases that occurred in the African continent.
The opposite occurred in relation to the New World. The search for parasites in wildlife eventually led to the discovery of a new trypanosome (T. minasense) in an endemic species of South American ape. Subsequently, an “unusual” insect (barber) was identified hosting an intermediate form of a trypanosome (critidia). Initially judged to be co-specific with the newly discovered marmoset trypanosomide, it turned out to be a distinct new species from T. minasense and pathogenic to humans. All of these great discoveries were made by a single scientist – Carlos Chagas – who through his search for new parasites discovered a new pathogenic protozoan (Trypanosoma cruzi), a new group of vector organisms (Triatominae subfamily hemiptera) and a new human trypanosomiasis (Chagas disease).
Carlos Chagas and the discovery of a new human trypanosomiasis
Simone Petraglia Kropf
Casa de Oswaldo Cruz/Fiocruz
In June 1907, Carlos Chagas was appointed by Oswaldo Cruz, director of federal public health, to combat a malaria epidemic that paralyzed the extension works of the Central Railway of Brazil in Minas Gerais, in the region of Rio das Velhas, between Corinth and Pirapora (Figures 1 and 2). In the municipality of Lassance (Figure 3), where a railway station was being built (Figure 4), he set up a small laboratory in a train car, which he also used as a dormitory. While coordinating the prophylaxis campaign, he collected species of Brazilian fauna, motivated by his growing interest in entomology and protozoology. In a context of international diffusion of theories of tropical medicine, these were areas of great importance in Oswaldo Cruz’s project to transform the Manguinhos Institute into a renowned center for experimental medicine. In 1908, when examining the blood of a marmoset, Chagas identified a protozoan of the genus Trypanosoma, which he named Trypanosoma minasense. The new species was a usual non-pathogenic monkey parasite.
At that time, the study of trypanosomes attracted the attention of researchers in the field of tropical medicine, especially since it had been shown that, in addition to animal diseases, protozoans caused human disease, such as African trypanosomiasis. Traditionally known as sleeping sickness, this disease caused great concern among European countries that had colonies on that continent.
In addition to searching for new parasites, Chagas was alert to arthropods that could serve as vectors. On a trip to Pirapora, he and Belisario Penna (his associate in the malaria mission) stayed overnight, along with the railroad engineers, on a ranch on the banks of the creek Buriti Pequeno. The head of the engineers, Cornelio Homem Cantarino Mota, then showed them a very common hematophagous bedbug in the region, commonly known as a barber (Figure 5), for the habit of stinging the faces of their victims while they slept. It was abundant in the region’s cob wall huts (“cafua”) (Figure 6), hiding in the cracks and holes in the mud walls during the day and attacking its residents at night.
Knowing the importance of blood-sucking insects as transmitters of parasitic diseases to humans and animals, Chagas examined some barbers and found in their gut flagellated forms of a protozoan, with certain features that made him think it might be a natural insect parasite or an evolutionary phase of the vertebrate trypanosome. In the case of this second hypothesis, it could be T. minasense himself, being the barber the vector that would transmit it to the marmosets.
Since he had no experimental conditions in Lassance to elucidate the issue, beacuse the monkeys in the region were contaminated, Chagas sent some of those insects to Manguinhos. Oswaldo Cruz fed them on laboratory-bred marmosets (and thus free of infection) and about a month later reported to Chagas that he had found trypanosome forms in the blood of one of the sick animals. Returning to the Institute, Chagas found that the protozoan was not T. minasense, but a new species of trypanosome, which he named Trypanosoma cruzi in honor of the master. The note announcing this discovery was written in Manguinhos on December 17, 1908 and published in the journal of the Hamburg Institute for Tropical Diseases.
In Manguinhos, Chagas began systematic studies on the evolutionary cycle of the new parasite (Figures 7 and 8), which, in compliance with two of Koch’s postulates, proved to be able to experimentally infect dogs, guinea pigs and rabbits and to be grown on agar-blood. The barber, in turn, was thoroughly investigated by Arthur Neiva, also a researcher at the Oswaldo Cruz Institute. In search of other T. cruzi vertebrate hosts and suspecting that the man might be one of them – hypothesis reinforced by his knowledge of malaria, also transmitted by a home-grown hematophagous insect and caused by a hematozoan -, Chagas returned to Lassance.
“We had taken, as a guiding idea, the notion that human households constitute the favorite, if not exclusive, habitat of the hematophagous, as well as the fact, widely verified, that human blood is its quintessential food. It would be reasonable to think, therefore, of an infectious condition within the household and that the parasite’s host vertebrate was some domestic animal or man himself”. – Carlos Chagas.
This hypothesis would also explain certain morbid phenomena he had observed in the region that did not fit the known nosological picture.
In Lassance, Chagas undertook systematic blood tests on residents and sought “the existence of characteristic morbid elements of trypanosomiasis” (Figure 9). Examining domestic animals, he verified the presence of T. cruzi in the blood of a cat. On April 14, 1909, he finally found the parasite in the blood of a feverish child. In a previous note sent to Brasil Médico, one of the country’s leading medical journal, announced the discovery:
“In a feverish patient, deeply anemic and with edema, with Pleiades engorged ganglionic, we find trypanosomes, whose morphology is identical to that of Trypanosoma cruzi. In the absence of any other etiology for the observed morbid symptoms and according to previous animal experimentation, we believe it is a human trypanosomiasis, a disease caused by Trypanosoma cruzi, whose transmitter is Conorrhinus sanguissuga.”
Berenice, a two-year-old girl, was the first case of what would henceforth be considered a new human disease. The fact was also disclosed through publications in the Archiff fur Schiffs-und Tropen-Hygiene and in the Bulletin de la Société of Pathologie Éxotique.
On April 22, at the same time that Medical Brazil was bringing in its pages the discovery made in the north of Minas Gerais, the fact was reported, in session of the National Academy of Medicine, by Oswaldo Cruz, who read a work written by Chagas. The press also highlighted the episode, revered as one of the “Glories of Manguinhos”.
The discovery and early studies of the new morbid entity had a decisive impact on Chagas’ scientific career, which reached great prominence in the scientific world, with direct effects on its insertion in the institutional life of Manguinhos. In March 1910, Oswaldo Cruz opened a contest to fill the vacancy of “Head of Service” opened with the departure of Henrique da Rocha Lima. This was an event of great importance to the institution, as the position’s occupant was seen as the most likely candidate for Oswaldo Cruz’s succession. Chagas took first place and the papers he had published on the new disease had a great weight on the outcome.
On October 26, 1910, Chagas was solemnly admitted as a full member of the National Academy of Medicine, where he gave a lecture presenting his clinical studies and presenting abundant material on the disease, including cinematographic images taken at Lassance. The following year, an event marked the dissemination of the discovery and of the new disease in the international scientific scenario. At the Brazilian pavilion of the International Hygiene and Demography Exhibition held in Dresden, Germany, Chagas disease was featured prominently, arousing great public interest. This projection expressed the importance that the theme assumed as the flagship and showcase of research at the Oswaldo Cruz Institute. Another important milestone in the international repercussions of the discovery was Chagas’s 1912 achievement of the Schaudinn Prize (Figure 10), awarded every four years by the Hamburg Institute of Tropical Diseases for the best work in protozoology.
Due to the repercussions of Chagas’ discovery and studies, Oswaldo Cruz obtained from the federal government special funds to equip a small hospital in Lassance (Figure 11) to host clinical studies on the new disease and to initiate in Manguinhos, the construction of a hospital for research and monitoring of clinical cases identified in northern Minas Gerais and other regions of the country. Under the leadership of Chagas and with the collaboration of several researchers from the Oswaldo Cruz Institute, the new trypanosomiasis began to be studied in its various aspects, such as the biological characteristics of the vector, the parasite and its evolutionary cycle, the clinical picture and the pathogenesis, epidemiological characteristics, transmission mechanisms and diagnostic techniques.
Becoming central in the institutional agenda of the Oswaldo Cruz Institute and in the very process of institutionalizing scientific activity in the country, the discovery of Chagas disease has been treated by contemporaries and medical memorialists to the present day as a glorifying myth of Brazilian science. One of the considerations that would become more recurrent as to the importance of the discovery as “one-off” of national science was the unusual character of the sequence in which it occurred, since it started from the identification of the vector and the causal agent to then determine the associated disease. Another singular aspect was the fact that the same researcher discovered, in a short period of time, a new vector, a new parasite and a new morbid entity.
The historiography on the discovery of Chagas disease highlights its inscription in the context of the affirmation and institutionalization of European tropical medicine, both due to the theoretical references that made it possible, as well as by the contribution that the discovery itself had in consolidating the new specialty created by Patrick Manson in the last years of the nineteenth century.
Another aspect highlighted by historians is the importance of the discovery as a source of legitimation, visibility and resources – material and symbolic – for Oswaldo Cruz’s institutional project. Benchimol and Teixeira emphasize that the main effect of the discovery was the consolidation of protozoology as a focus area of the Institute’s research, as well as the drive to recognize Manguinhos in the international scientific community as a center for research on tropical diseases. Kropf points out that if, on the one hand, the discovery contributed to make sense and reinforce Manguinhos’s institutional project, it also gained particular meanings as a “great achievement of national science” due to the meanings associated with this project, which is it publicly presented as designed to link academic excellence and social commitment to identifying and solving the country’s health problems.
Carlos Chagas e a caracterização clínica da tripanossomíase americana (1909-1934)
Simone Petraglia Kropf
Casa de Oswaldo Cruz/Fiocruz.
The first characterization of the clinical picture of American trypanosomiasis, discovered in 1909, was presented by Carlos Chagas in October 1910, in a conference at the National Academy of Medicine. In addition to the clinical observation data performed in Lassance, the histopathological data produced by Gaspar Vianna, also a researcher from Manguinhos, were fundamental to its composition.
Chagas divided the infection into two modalities: acute and chronic. The acute phase was classified into two forms: 1) cases with severe brain disorders, such as meningoencephalitis, derived from the action of T. cruzi on the central nervous system, and usually composed of children under one year old, who almost never survived; 2) cases without such manifestations, with a more benign prognosis, that, between 10 and 30 days, evolved to the chronic state, with the regression of the symptoms of the initial period. Due to the abundance of trypanosomes in the blood circulation during the acute period, the parasitological diagnosis was made by direct observation of the blood.
Of the symptoms of the acute period – continuous and intense fever, ganglia in the cervical region, armpits and inguinal region, splenomegaly, hepatomegaly, nervous system disorders (meningism phenomena), cardiac disorders and eye disorders – Chagas highlighted some signs that, by their constancy should be privileged as elements of disease specificity and, consequently, as a basis for clinical diagnosis. Expressing what, according to him, was a thyroid disorder derived from the pathogenic action of T. cruzi on this gland, the main one of these signs would be facial swelling (myxedema), which is very common in children since the early days of infection and conferred to the patients characteristic facies.
The chronic phase comprised most patients and consisted of endocrine, cardiac and neurological elements. For Chagas, the most constant and salient clinical feature of the new trypanosomiasis was the functional thyroid disorder, expressed mainly by hypertrophy of the gland (goiter or “maw”) (Figures 1 and 2). In May 1910, he had published a note formulating the hypothesis of parasitic etiology of endemic goiter.
This thyroid disorder, which was associated with physical and mental disorders constituting endemic cretinism, has been known since ancient times and has been described above all in the mountainous regions of the European Alps. By the end of the XIX century, its etiology had not yet been fully elucidated. Some credited it with the chemical deficiency of iodine in water, while others considered the action of microorganisms. Endemic goiter had a high prevalence in Minas Gerais and, since the XVIII century, attracted the attention of naturalists, travelers and doctors. The physical disfigurement it caused, especially when it reached large volumes, and the association with cretinism, was considered one of the main reasons for the backwardness of mining peasants.
According to Chagas, in Minas Gerais and other regions where there was T. cruzi transmission, endemic goiter was not the same nosological entity as in Europe, but a consequence of the action of this parasite on the thyroid. His conviction was based on three orders of evidence. First, he observed clinical signs of hypothyroidism in individuals with other signs of trypanosomiasis, both in the acute and chronic phase (including exclusively breastfed infants, which, he said, disproved the hypothesis related to chemical deficiency of water). In addition, autopsies revealed thyroid lesions that, according to him and Vianna, would be caused by the parasite. Finally, the epidemiological data: “So far, from personal observations and information gathered, in the regions of Minas, where goiter exists, there is also the insect transmitting schizotrypanosis”. Based on these arguments, he concluded:
“Whether the European endemic goiter of water or infectious origin, the one we have been studying in our home state, is undoubtedly a parasitic thyroiditis syndrome, a very happy name created by the illustrious Professor Miguel Pereira.”
Considering the effects of thyroid impairment on the organic development of individuals, this has become one of the main ways in which Chagas would affirm the medical and social importance of the disease, as a “chronic morbid condition that renders the individual unusable for vital activity” and as “an important factor of human degeneration.”
Endocrine disorders of the chronic phase, according to Chagas, varied in intensity and so he classified them into two clinical forms: pseudo-myxedematous and myxedematous. The first would be the most prominent, comprising the vast majority of carriers of the infection. These were children or young people who, having survived the acute phase, suffered the still mild effects of hypothyroidism. The thyroid enlargement was still incipient, not characterized by the large volume that, after a progressive evolution, would have in some adults. The myxedematous form would cover the less common cases of greater severity of thyroid involvement. Instead of hypertrophy of the gland, its atrophy was observed, that is, the total destruction of the function, with extremely debilitating effects.
The third form of chronic infection would be the nervous form, whose signs, especially in children, would be motor disorders (such as diplegia), language (such as aphasia or dysarthria) and intelligence, such as idiocy (severe mental retardation) and dementia. Along with the thyroid enlargement, such disorders, attributed to the action of the parasite on the central nervous system, would take great prominence in Chagas’ statements on the severity of the physical and social effects of the disease. Just as in the acute meningoencephalic form, the allusion to “creatures condemned to the existence of monsters” would become frequent in this respect as well.
Another clinical syndrome of the chronic phase was the cardiac form. The most characteristic signs derived from parasitic localization in the “noble element of the myocardium” would be certain changes in heart rhythm, such as extrasystoles (excitability disorder) and, to a lesser extent, disturbances in stimulus conduction, such as heart block. Unlike other forms, which preferentially affected children, Chagas observed the presence of these phenomena in individuals from about 16 years. The prognosis was generally severe, leading to heart failure and, in some cases, sudden death from asystole. This was one more aspect of the medical-social impact of the disease, he stressed, as it compromised the vitality of individuals at full working age.
As for the diagnosis, in the chronic modality, unlike in the acute phase, the parasites were not in the bloodstream, which prevented the parasitological demonstration by direct observation of the blood. The procedure used in these cases was the inoculation of the “suspicious” blood in guinea pigs. Once the animal died, the identification of schizogonic forms in its lung (which Chagas considered evolutionary stages of T. cruzi) would determine the positivity of the diagnosis. This method would be abandoned in 1913.
Despite the incipient stage of the research, as early as 1910 Chagas pointed out that the presence of the barber had been attested in “almost the whole of northern Minas Gerais, in vast regions of the west of the same state, and also in the states of Mato Grosso and Goiás”, which allowed him to speculate that “the extent of the country where schizotrypanosis will rage” will be vast. Such data came mainly from the studies of Arthur Neiva, who was dedicated to entomological studies in Manguinhos.
From this first clinical design of the disease, the following fundamental features stand out: it was an essentially chronic infection, with progressive evolution, contracted in the early ages, by practically all those who lived in barber-infested dwellings and that, by reaching the individuals in the midst of physical and mental development produced permanent impacts on their vitality and organic development. Its main clinical manifestations were endocrine (mainly thyroid), nervous and cardiac disorders.
Despite attaching importance to these three axes of the clinical picture, Chagas gave a clear emphasis to the first of them. One of the main indications of this primacy was the name, proposed by Miguel Pereira and widely used by Chagas, to refer to the disease: parasitic thyroiditis. In the expression of another renowned physician of the time, Miguel Couto, thyroid hypertrophy was the hallmark of the disease and became the most prominent feature in the visualization of the new medical entity. Thyroid enlargement was thus seen as the primary sign for the clinical diagnosis of infection.
Since 1910, Chagas publicly defended the notion that the new trypanosomiasis was a disease of great medical and social importance. Using a rather recurring term in the intellectual debate of the time, it would lead to the physical and mental “degeneration” of rural populations, undermining the country’s productivity and progress. It should therefore be firmly fought by the public authorities. At his conference at the National Academy of Medicine, he warned:
“It is very painful the impression brought by the morbid facts observed in those zones; painful for the doctor, who in the current resources of science does not yet find an effective means of combating the terrible enemy; painful for the statesman who is slow to reason about the obstacle fatally brought by that morbid condition to any attempts at collective progress; painful, finally, for the altruist, who will observes human misery there in its fullest expression, whatever the fatality of a chronic disease, capable of rendering mentality, intelligence, vital activity, life normal condition necessary for human happiness.”
His statements had a big impact. They unveiled, before the medical and political elite of the federal capital, the portrait of the disease and the poverty in the interior of Brazil. The fundamental precept was then stated that, throughout the 1910s and especially after the outbreak of World War I, would be amplified in the so-called sanitary movement: the idea that overcoming the ills of Brazil depended on state intervention for the sanitation of their backlands. By the end of his life, Chagas would emphasize the need to prevent and combat this and other inland endemics as a path to “health redemption” and the economic progress of the country’s rural populations.
In 1911, Chagas deepened his clinical classification, reiterating the primacy given to endocrine elements and his conviction regarding the parasitic etiology of endemic goiter. In addition to thyroid disorders, he pointed to the presence of ovarian and adrenal deficiencies, even proposing, for this last aspect, the creation of a specific clinical form.
From 1913 onwards, the process of defining and recognizing the new trypanosomiasis as a specific nosological entity would take a new course. Studies started by Henrique Aragão proved that the schizogonic forms found in the lung of experimentally infected guinea pigs (which Chagas thought were evolutionary stages of T. cruzi) corresponded to another parasite, Pneumocystis carinii. Besides leading to a review of the parasite’s cycle, such studies invalidated the main parasitological diagnostic method used by Chagas for chronic forms of trypanosomiasis. From then on, despite the proposition of new diagnostic methods – such as the complement fixation-based serological test, developed by César Guerreiro and Astrogildo Machado in 1913, and the xenodiagnosis, proposed by Émille Brumpt in 1914 – the uncertainties regarding the parasitological confirmation of chronic cases would raise questions about the clinical definition of this modality of infection.
In 1915/1916, studies in Argentina under the leadership of microbiologist Rudolf Kraus of the University of Vienna confronted some statements by Chagas for the chronic forms of trypanosomiasis, especially the hypothesis of parasitic etiology of endemic goiter. Despite the proven distribution of infected “vinchucas” in Argentine territory, the researchers were concerned that no human cases of the disease were diagnosed. They reported that in provinces where vectors were present, goiter was often not identified; or when they were found, infection with that parasite could not be proven. Kraus and his colleagues then argued that the thyroid and nerve manifestations attributed to American trypanosomiasis corresponded in fact to the endemic goiter and cretinism already described in Europe, attributed by many to iodine deficiency.
In response to these questions, Chagas published in 1916 three important papers in which he reiterated his convictions about endocrine and neurological impairment in trypanosomiasis. However, even reaffirming his statements, Chagas began to give them new emphases and meanings, minimizing the primacy attributed to thyroid signals and reinforcing the importance of cardiac elements. In an extensive work published in 1916, he established new terminology for the classification of chronic forms, replacing the “pseudo-myxedematous” and “myxedematous” forms, respectively, with “indeterminate form” and “hypo-thyroid form”. In the first case, relatively recent chronic cases would be assembled, which did not yet manifest “the profound anatomical alterations that determine definitive clinical syndromes”. They would constitute, according to him, “forms of passage”, by indeterminacy in their clinical physiognomy.
Affirming that “in trypanosomiasis thyroid insufficiency is only one of the elements of the disease and is not in itself the nosological entity”, Chagas endeavored to ensure that even if such an aspect were discarded, this would not rule out the disease. existence of the disease as an “autonomous disease (…) characterized by well-determined symptomatology and well-grounded in histopathological lesions”.
In very significant discursive operations of the movement whereby American trypanosomiasis was no longer characterized as a fundamentally endocrine disorder, endemic goiter – hitherto seen as a ‘seal of the disease’ – has come to be described as “a debatable problem attached to the clinical history of the disease. trypanosomiasis”. From then on, Chagas stopped using the term parasitic thyroiditis to refer to the disease.
The guideline adopted in this “new framework of the clinical picture of the disease”, begun in 1916, was the progressive appreciation of cardiac aspects. In 1922, in partnership with Eurico Villela, Chagas published extensive work on heart shape, which, according to the authors, should be seen as “the quintessential clinical feature of American trypanosomiasis.”
Ironically, in the same year of 1922, an intense controversy began at the National Academy of Medicine (Academia Nacional de Medicina), in which a group of physicians challenged various aspects of Chagas’s work, restating the doubts cast in Argentina, especially the correlation with goiter and the idea derived from it, that the disease was a vast endemic of great medical and social impact. Although Chagas has come, since 1916, stating that the hypothesis about goiter could be revised, the great political visibility given to the American trypanosomiasis, between 1916 and 1919, within the scope of the sanitary movement had reinforced, by the social dramatic that imposed to the clinical design. that endemic, precisely the aspects that were most objected in the field of scientific discussion: the thyroid enlargement and nervous disorders.
At the conference at the closure of this controversy, Chagas continued by stating that, even if one refuted the goiter statements and other formulations, one could not doubt the “inescapable signs” that grounded American trypanosomiasis as a real and specific clinical entity. He again pointed to the heart shape as “the most interesting and characteristic feature of American trypanosomiasis.”
Although less intense than the cardiac form, the nervous form, although contested, would still motivate the research of Chagas and his collaborators. Beginning in 1923, experiments by Eurico Villela and other researchers, who reproduced paralysis and other neurological disorders in dogs inoculated with T. cruzi, were seen as reinforcing the thesis of this protozoan’s special “predilection”, at least of some strains by the nervous system. Animal studies also demonstrated congenital intrauterine transmission of T. cruzi. At a time when the doctrines in neurology postulated that congenital infections were the most conducive to nervous system impairment, the notion that the pathogenic action of that parasite on such an organic system took place from embryonic life was strengthened.
In 1932, in his last scientific presentation on the disease, Chagas presented a systematization of the “current state of American trypanosomiasis”, whose objective was to highlight precisely the advances in the understanding of the nervous form. After expressing his enthusiasm with the impetus given to this aspect, the work approached the heart shape, reaffirming its central importance:
“The varied alterations of the heart rhythm constitute the most valuable symptomatic characteristic for the clinical diagnosis of this infection; (…) The endemic index of American trypanosomiasis should be appreciated mainly by the ever-high percentage of individuals with heart rhythm disturbances.”
The other clinical modalities of the disease, including endocrine syndromes and goiter, were, according to him, “less enlightened aspects”. He said:
“Although persistent in the previous conviction, we must confess that the subject offers room for disagreement, being subject to challenge to the formulated doctrine. … It is an open question, worthy of study and insight.”
Following the death of Chagas (1934), it was confirmed that American trypanosomiasis and endemic goiter were overlapping and totally distinct endemics. As well as his statements about endocrine forms, the chronic nervous form would also be abandoned.
However, his formulations of the heart form of the disease would be widely confirmed and expanded, especially from the research of his followers in Manguinhos, such as Evandro Chagas and Emmanuel Dias. The latter, director of the Chagas Disease Research and Prophylaxis Center – an IOC advanced post established in 1943 in Bambuí, Minas Gerais – produced, along with the cardiologist Francisco Laranja, works that would consolidate the characterization throughout the 1940s of chronic chagasic heart disease as the main clinical expression of Chagas disease.
In the 1950s, based on the work of Joffre M. de Rezende and Fritz Koeberle, another statement that Chagas had proposed in 1916 (albeit deepening later) was proved: that the “choking disease” or megaesophagus is due to pathogenic action of T. cruzi. The digestive form (megaesophagus and megacolon) then became, together with the cardiac form and the undetermined form, the clinical picture of chronic infection.
The Centenary of the Patient Berenice (1907-1981)
João Amílcar Salgado
Faculdade de Medicina, Universidade Federal de Minas Gerais
In 2007 we celebrated two centenarians that should be considered symbolic in the history of Chagas disease. If alive, they would be one hundred years old the patient Berenice, through whom Carlos Chagas discovered the disease that bears his name, and Professor Amílcar Viana Martins, the remarkable parasitologist who, in 1961, referred us to the same patient for complete clinical reevaluation.
At the beginning of 1961, in a meeting of Chagas disease researchers, Professor Amílcar Viana Martins lamented that in the fiftieth anniversary of the disease, celebrated two years earlier, there was still no real survey of acute cases. He regretted, therefore, the absence of field-willing clinicians who would be the ideal investigators for such survey. He asked me if I was willing to perform such task. I accepted with enthusiasm and soon presented a detailed project.
The conditions were favorable, as Martins had commanded both the National Department of Rural Endemics and the Oswaldo Cruz Institute, while Celso Afonso de Oliveira and I, a recent graduate, were in charge of integrating the University of Minas Gerais (now Federal University of Minas Gerais) and the Research Center of the former National Institute of Rural Endemics (now the René Rachou Research Center of the Oswaldo Cruz Foundation). Unfortunately, the resignation of President Jânio Quadros brought severe political crisis that made that initiative unfeasible.
Soon the discouragement was replaced by new enthusiasm. Dr. Paulo Nogueira Garcez, from Pirapora and doctor from the Oswaldo Cruz Institute, refer to Professor Amílcar Martins a lady that he was almost certain was Berenice, the girl whose blood was analyzed by led Carlos Chagas leading to the discovery of the disease that bears his name, in 1909. Martins asked me to admit her directly to the university hospital and to protect her from any sensationalism.
She told Dr. Garcez that she herself was the patient examined by Dr. Carlos Chagas. Other details that she provided led him to near certainty. We soon took steps to fully identify her, which, however, took longer than expected. Finally, the collected data allowed to transform the near certainty in certainty. This investigation, parallel to clinical and parasitological investigations, eventually turned me into a specialist in medical history.
The hospitalization of the patient Berenice couldn´t be done better, since the Chair of Medical Propaedeutic Clinic of the current Federal University of Minas Gerais, headed by Professor João Galizzi, enjoyed great ethical and scientific respectability. In addition to this famous semiologist, who has trained generations of excellent clinicians, I counted on the researcher and professor Celso Afonso de Oliveira, already mentioned, the PhD student Adaílton de Campos Belo and all the helpful staff of the Red Cross Hospital, at the time an annex to Clinical Hospital.
From the first xenodiagnosis, it was possible to isolate the trypanosome we call the sample or strain Berenice. This rare fact in xenodiagnosis caused, beyond surprise, great emotion, because we were probably observing the same parasite observed by Carlos Chagas at the time of his discovery. Xenodiagnosis and isolation were made with the essential participation of the parasitologist Helio Espinola and with the supervision of Dr. Aprigio de Abreu Salgado, national expert on xenodiagnosis. The names of these two researchers and Professor Amílcar Martins would appear in the second publication to be made, with the exclusive data from the Berenice sample. Unfortunately, it did not occur, but the sample was better characterized by comparative studies with other samples. Thus, the initial publication was restricted to the clinical report entitled Current Clinical Review of the First Described Human Case of Chagas Disease, published in the Journal of the Institute of Tropical Medicine of São Paulo, September-October 1962, by authors João Amílcar Salgado, Paulo Nogueira Garcez, Celso Afonso de Oliveira and João Galizzi. In the centenary of Carlos Chagas, in 1979, I participated in the celebration with the article The Centenary of Carlos Chagas and the Girl Berenice, published in the Memórias do Instituto Oswaldo Cruz.
The patient Berenice was followed clinically for twenty years until her death in 1981, with no evidence that her death could be attributed to Chagas disease. Full details of the medical observation will be included in the book set to commemorate the hundred years of discovery. It was emphasized the identification of the patient, the clinical and parasitological aspects, as well as the ethical care applicable to this specific type of doctor-patient relationship and the special character of the report. Epidemiological data and historical circumstances of the discovery are discussed as well as the evolution of the knowledge about the disease from the initial announcement made by Carlos Chagas and the impact of news about the patient survival.
An example of this impact was our own attempt to systematize the evolutionary alternatives of the disease in order to better follow the patient. In fact, in 1963, a year after our initial publication, and in collaboration with Cid Veloso and Arnaldo Antônio Elian, we presented in Salvador, at the XIX Brazilian Congress of Cardiology, the study entitled Critical review of data that underlies prognosis and therapy. the chronic form of Chagas disease, and we published it in the journal Arquivos Brasileiros de Cardiologia (June 1964). It was the effort to interpret, according to the latest advances in science, the scarcity of manifestations and the long survival of the patient, both observed precisely in this example, where the infection was the longest proven.
Luckily, by this time, the first cardiologic results of the space race were emerging. We sought to apply to Chagas disease such emerging data found in the book Cardiovascular Dynamics by Rupert F. Rushmer. We based on 105 observations of Chagas disease patients, mostly from Minas Gerais, divided into two groups: 80 were hospitalized or were outpatients, some were submitted to pharmacological tests, and 25 were workers, examined in an endemic area of the west of the state (Calciolândia). The doctoral student Antônio Dílson Fernandes accompanied this research, and became later an extraordinary cardiovascular surgeon. The presentation of the data earned us compliments of Luis Venere Decourt, the noted Brazilian cardiologist, who was excited about the line of study and urged us urgently to further develop the research.
Also, I decided that my first thesis, which became a master’s degree, would be on experimental research dealing with the Berenice strain, while the doctoral thesis would cover the respective laboratory, clinical, epidemiological and historical research. The first was entitled “Study by intestinal perfusion method of jejunal absorption of glucose in rats chronically infected with Trypanosoma cruzi”, presented in 1976 including the strains Berenice, Y, PNM, CL and FL. This work had the fundamental support of Zigman Brener, Joao Paulo Mendes de Oliveira, Tarcisio de Campos Ribeiro, Washington Tafuri and Luiz de Paula Castro. The theme of the doctoral thesis was modified, due to academic priority, to the area of medical education, leaving the complete study of the Berenice case for the full professor thesis.
For the post of titular professor in 1981, shortly after Berenice’s death, the thesis presentation, according to the new norms, was transformed into a seminar. I made an oral presentation of the complete study that I had been preparing since 1961 and that would be later published on the centenary of the discovery. I was very honored by the enthusiastic compliment of Fulvio Pillegi, a worthy and righteous man of science, and member of the examining board. I think it is appropriate to say that I included in this seminar my detailed and critical investigation of the hypothesis that Charles Darwin was the victim of Chagas disease. I have been studying this hypothesis since 1961, in response to a personal request made by Saul Adler, who was, at that time, visiting researcher of leishmaniasis, in our aforementioned Research Center.
Finally, let us return to a fact that occurred shortly after the publication of the Berenice case in 1962: an episode described in my memoir entitled The Golden Laughter of the Village. It coincided that, in those days, there was a congress of pathologists in Belo Horizonte, in the very premises of the Faculty of Medicine. They tried to get me ready, because I was likely to be called out to testify on the subject. I followed two sessions until, in the third, a well-known Chagas disease researcher said that, as a Brazilian, he recognized that Brazil had a lot to evolve in science. Since, he continued, an entirely unknown individual from the scientific community had published something about Carlos Chagas’s discovery, which scholars in the field could not give credit for. He regretted that a serious journal had welcomed the text, for all those like him who knew the history of the disease, knew that the first patient had not survived the acute phase. I was so shocked by such declaration that I left the room. Just in the courtyard of the College, I found Professor Amilcar Viana Martins and told him what happened. I expected him to react with indignation, due to this temperament. Instead, he began to laugh and said his phrase often quoted, sometimes attributed to someone else: you are very young, now you know that in Brazil there are more people living than dying of Chagas disease.