Insects, people and disease: Adolpho Lutz and tropical medicine

These physicians, especially those from the São Paulo commission, made daily house calls to the sick in the city's four districts. They inspected swamplands, latrines, wells, and deposits of used water, closing some down and spreading large amounts of antiseptic

agents (mainly ferrous preparations, sulphurous gas, 29 and carbolic acid) over all possible sources of yellow fever, including victims’ caskets. The Municipal Chamber even threatened to break into the houses of those who had fled in order to disinfect them (Santos Filho and Novaes, p.45).

“A great deal of money was spent (not only in Campinas but in other towns as well) on disinfectants that were poured into latrines, and drinking water was brought in from other places, while mosquitoes were allowed to breed as they liked,” Lutz would later write, when views on transmission of the disease had already changed radically (Lutz, 1930, p.142).

At that time, water was incriminated as a possible etiological agent. As water lines had yet to be laid in Campinas, starting on 17 April, the Companhia Paulista de Estradas de Ferro shipped 24,000 liters per day from Valinhos to the tanks that fed the city's public water fountains, and the Municipal Chamber provided water trucks to transport it to outlying areas. According to Santos Filho and Novaes, the São Paulo commission signed twenty-seven death certificates in April and May, a very small number in comparison with the overall number of lives claimed by the epidemic. This total displayed the signatures of only four physicians, most (i.e., fifteen) signed by

Adolpho Lutz, “who attended the greatest number of patients.”30 The cited authors argue that the first number was so low because those doctors’ job was “essentially prevention and disinfection.” They also note that the number of patients admitted to hospitals was low as compared to those treated at home; people were terrified of hospitals and, as in many other towns, regarded them as “death chambers.” Consequently, some doctors made “about ninety house calls a day” (Santos Filho and Novaes, p.10).

As the epidemic wound down, only Góis, Homem de Melo, and two disinfectors remained in Campinas. Of the group sent by the central government, those who stayed behind were Correia Dutra (who had taken over as head of the commission following the return of José Maria Teixeira) and Eufrásio José da Cunha, as well as the academics Vito Pacheco Leão and Alberto de Castro Meneses (Santos Filho and Novaes, p.57). They were the last to leave the town, in late June or early July. The district judge reopened the court that month, and on 15 July classes resumed. Campinas “arose from the ashes, and the risen phoenix was purposely chosen as the city's

symbol”.31

 

Yellow fever spreads through Southeastern Brazil

In the modern history of yellow fever in Brazil [wrote Adolpho

Lutz (1930)] the most ill-fated year was 1889, when it hardly

ever rained for three months during the hot season and the

temperature reached highs not seen other years. In Rio and in

Santos, severe and rapidly fatal pyrexias appeared in epidemic

form. Never seen before, these fevers were generally classified

as “pernicious fits” or, more rarely, as “fulminating yellow fever.”

Only after much discussion was it recognized that the fevers

were caused solely by the high temperatures – called heat

stroke in the vernacular.

That same summer … in Santos, where there had been no

yellow fever for ten years, the epidemic was very severe. In

fifteen days, the German Club lost one-fourth of its members.

In the month of March alone, the city saw 580 deaths due to yellow fever, according to Santos Filho and Novaes (p.38), or 650 according to Freire (1890a), 500 of whom were recent immigrants. In Rio de Janeiro, 2,408 people perished in 1889 (1,926 immigrants), according to this same source. The first authors put the number of deaths at 2,156. The figure rises if we include deaths in Niterói, across the bay from Rio: 177, of whom 63 were immigrants.

Lutz (1930) makes mention of the appearance of yellow fever in Rio Claro and Belém do Descalvado. Other cities invaded by the disease were Cataguases (MG); Barra Mansa, Vassouras, and Resende (Rio de Janeiro); Desengano (Espírito Santo); and Serraria (Rio de Janeiro), once again, part of the population in these places fled,

including physicians. 32

The outbreaks in these cities did away once and for all with the notion that yellow fever was specific to intertropical coastal regions. It was not without reason that physicians searched so persistently for its chemical or biological agent in the holds of ships, comparing these to the unhealthy housing of port cities.

Loading coffee in the port of Santos. Photograph by Marc Ferrez

taken in 1880 (Walker & Braz, 2001, p.45).

Accompanying the tide of immigration that swept into Brazil following the collapse of slavery and the upsurge in economic prosperity during the passage from monarchy to Republic, the spread of yellow fever placed on the agenda a controversy that would only grow more heated with each successive epidemic peak in the 1890s: was this “American typhus” an illness deeply entrenched in Brazil or a constantly imported ‘pestilence’, a disease that could be yanked out by the roots through drastic environmental intervention, or a contagious illness that would only respond to palliative measures or attenuating agents?

“Back then,” wrote Lutz (1930), “many people still believed in direct contagion, and black vomit was deemed a kind of essence of yellow fever.” No other infectious disease was so easily transmitted via inanimate bodies, stated João Batista de Lacerda. Dr. Antônio Caio da Silva Prado, president of the province of Ceará (1888-1889), represented the paradigmatic case of this viewpoint: he died on 25 May 1889, after receiving letters and newspapers from infected Campinas. This and similar cases would often be posited as unquestionable proof that the yellow fever germ was transported by a wide gamut of objects: the infective matter clung to clothing, to coal, to fruit peels, to stationery; entering the holds of ships and train cars, it could travel great distances (Lacerda, op. cit., p.16-30; Brazil-Me- dico, 8 Jun. 1899, p.212-4).

Proponents of the idea that yellow fever was transmitted by mosquitoes would later have to work hard to refute the “monolith that is constantly hurled against the new doctrine” – the case of Caio Prado and similar others (Quinto Congresso, p.36, 150).

Adolpho Lutz's Reminiscências was written when mosquito transmission had already become established. For him, propagation of the disease after being ‘exported’ from Rio de Janeiro to Campinas could be explained by the following set of factors: Stegomyia fasciata had been disseminated, and infected people were moving into or through regions inhabited by people lacking immunity to the disease.

Campinas saw outbreaks in 1890, 1892, 1896, and 1897. The worst took place in 1896, but “it no longer elicited the same manifestation of solidarity. Everyone accepted things. There was no longer a stampede of physicians or any charity drives” (Santos Filho and Novaes, p.35, 10).

For Adolpho Lutz (1930), infected mosquitoes carried by rail lines accounted for the 1889 outbreaks in Rio Claro and Belém do Descalvado, and also for a number of isolated cases among mail carriers and railroad workers, including “a lady in Valinhos, who was married to the stationmaster and lived in the stationhouse. She had never been to Campinas while yellow fever was there.” In subsequent years, in the words of Lutz, the disease:

invaded the state of São Paulo, primarily following the Paulista

railway. It ravaged Limeira, where I had maintained a private

practice for five years without ever seeing Stegomyia but it

spared Araras and Jundiaí, where the villages are located quite

far from the train stations. After the Paulista [railway], the

Mogiana was invaded, and only much later came the

Sorocabana's turn. What unquestionably kept it from spreading

faster was that the numerous cases among those who fled the

centers of epidemics could not spread the yellow fever, without

the prior or simultaneous import of Stegomyia.

Back when these outbreaks were erupting, the explanations that were viewed as the most innovative no longer associated the disease with miasmas inseparably tied to certain environments; instead, it was believed to be associated with microorganisms that could travel through different environments and from person to person, airborne or by other means. The overriding belief was that the germ underwent some kind of transformation in the external environment before it became infective, yet only in some geographical zones and during a certain season of the year.

 

In search of the yellow fever microbe

When Adolpho Lutz began his career in the early 1880s, the issue of microbes was kindling heated discussions over the disease that was then Brazil's number-one public health problem. December was the month when the merciless sun of the ‘muggy season’ beat down on the streets and houses of Rio de Janeiro, or when these were submerged under torrential rains. It was in that month in 1879, that Dr. Domingos José Freire, who held the chair in organic chemistry at

Rio's School of Medicine,33 announced in the papers his discovery of a microbe which he believed to be the cause of yellow fever. In the “humors” of sick people he had found granules and Vibrio that took the form of black corpuscles as they developed. He contended that the detritus and countless spores released by them lent the patient's vomit its characteristic black color (Gazeta de Noticias, 23 Feb. and 29 Feb. 1880).

In the first half of 1883, using techniques recently discovered by Louis Pasteur, Freire developed a vaccine against the disease by attenuating the microscopic algae that he called Cryptococcus xanthogenicus. The only other prophylactic measure of this kind then applicable in fighting human diseases was the smallpox vaccine. Pasteur's achievements in this area were still limited to vaccines against chicken cholera (1880) and anthrax or haematic carbuncle (1881). Pasteur's debut in the realm of human pathologies, with the anti-rabies vaccine, would involve complex social and technical constraints overcome only in 1886, as Geison (1995), Debré (1995), Salomon-Bayet (1986), and others have shown.

A crisis involving the smallpox vaccine in Bahia catapulted Freire to the presidency of the Central Board of Public Hygiene in late 1883, facilitating dissemination of his vaccine against yellow fever among

Rio de Janeiros tenement dwellers. 34 He enjoyed a surprisingly warm welcome among immigrants and then among native-born Brazilians, not only because the disease had incited such fear but also thanks to support from republicans and abolitionists with whom he had ties.

Reactions were contradictory both in the press and at the Imperial Academy of Medicine, especially after the vaccine received the tacit support of Emperor Dom Pedro II and the enthusiastic backing of one of Pasteur's ‘disciples’, Claude Rebourgeon, a French veterinarian hired by the Brazilian government to begin production of an animal vaccine against smallpox in Rio Grande do Sul. Rebourgeon presented Freires discovery before the academies of medicine and of science in Paris (Freire and Rebourgeon, 1884). Important figures in French medicine responded favorably, including the pathologist Alfred Vulpian and the veterinarian Henry Bouley.

Caricature of Dr. Domingos Freire, the physician who invented a

yellow fever vaccine, by Angelo Agostini (Revista Illustrada, 1889,

year 14, n.533, p.8. Arquivo Geral da Cidade do Rio de Janeiro).

It should be mentioned in passing that both Pasteur's 1881 efforts to identify the yellow fever microbe as well as Emperor Dom Pedro II's efforts to entice him to Brazil to decipher the disease met with failure

(Vallery-Radot, 1951). 35

Between 1883 and 1894, at least 12,329 immigrants and native-born Brazilians in Rio and other cities around the country were inoculated with Freire's vaccine, which reached Puerto Rico, Jamaica, the Guianas, and other French colonies too (Benchimol, 1999, p.119-68). The dissemination of this invention was partly due to the increasingly complex web of relations entwining the Brazilian bacteriologist with a number of other actors: colonial and business interests, other microbe hunters, medical and scientific associations, and the authors of treatises systematizing achievements in microbiology.

During his stay in Europe between December 1886 and July 1887, Freire submitted two special communications to the Academy of Sciences in Paris, co-authored with Rebourgeon and with Paul Gibier, a researcher from the Natural History Museum in Paris (Freire, Gibier, and Rebourgeon, 1887a and b). This and other events in the French capital made a strong impact in the Brazilian capital, and upon his return Freire was received as a hero of Brazilian science by students and professors at technical schools and universities in Rio de Janeiro, Minas Gerais, and São Paulo, by journalists from a variety of periodicals, and by militant members of republican clubs and abolitionist societies. Weeks later he traveled to Washington to participate in the 9th International Medical Congress, which approved a resolution recommending his vaccine for all

countries afflicted with yellow fever.36

A measure of the vaccine's social and geographic reach is apparent in the quantity and quality of the names that certified Freire's statistical data or that reported on post-vaccine symptoms, endorsing the immunizing action of his prophylactic liquid; it is further reflected in the number of physicians and authorities involved in its dissemination.

During 1883-84, a handful of people from Vassouras were

vaccinated.37 On 6 February 1889, when the city's Municipal Chamber met to decide what means should be used to keep the disease from invading once again (the city had already been hit twice), the decision to employ the vaccine was unanimous. The terms of the letter to Freire show how far his reputation had come. They entreated him to give the frightened population access to “individual means of prevention, unquestionably more reliable than general means, and whose discovery and popularization are due to … your immeasurable talent, [as you knew how] to earn not only the blessings of the fatherland … but likewise an eminent place among

humanity's benefactors.” 38

Joaquim Caminhoá (son), Freire's assistant, vaccinated 199 people there.

The appeals sent by the Chambers of Pomba, Macaé, and Niterói were no different. The first city requested a shipment of the vaccine liquid in June, after the disease had struck neighboring Cataguases (MG), where vaccination was performed by Dr. Araújo Lima. In Macaé, Dr. Carneiro Mattoso, physician for the Chamber and public hygiene delegate, undertook the task. In Niterói, 163 vaccinations were administered, a good share by Freire himself, right inside the Chambers in the presence of its president, Prosper David, and of the physician Victor David and the city aldermen. The hygiene inspector for the province of Rio de Janeiro, Dr. Henrique Baptista, was responsible for going from residence to residence. At the end of the campaign, the Chamber offered use of one of its rooms so the scientist could continue his “humanitarian work” throughout 1889. In Juiz de Fora and Serraria (MG), a local physician, Dr. Avelar Andrade, was responsible for vaccinating 30 and 50 people, respectively. The 54 inoculations in Resende (Rio de Janeiro), all involving native-born Brazilians, were also performed at the initiative of two local physicians, Drs. Gustavo Gomes Jardim and Carlos Augusto de Oliveira e Silva. In Desengano (Espírito Santo), the epidemic was combated by Dr. Henrique Baptista, with two other physicians assisting: Rodrigues Guião, public hygiene delegate, and Edmundo Lacerda, local clinician. Of the city's 425 inhabitants, 102 received what was allegedly an ‘attenuated yellow fever virus’ (24%).

The disease reached Santos. At the Municipal Chambers, under the eyes of the town's most prominent citizens, 133 people were inoculated in February 1889 by Dr. Barata Ribeiro, professor from

Rio's School of Medicine.39

On 9 March, José Paulino Nogueira (mentioned earlier), president of the Campinas Municipal Chamber, asked that the Inspector of Public Hygiene for the Province of São Paulo send, “as urgently as possible, a quantity of vaccine fluid against yellow fever, which has been requested by some municipalities” (Santos Filho and Novaes, p.46).

Angelo Agostini uses humor to decry water shortages, which

became acute in the Summer months, yellow fever season. Yellow

Fever observes a discussion of “microbe vaccination” between the

president of the Board of Hygiene (Freire) and the health

commission. Agostini makes fun of the precautions against

contagion from Brazil taken by neighboring countries on the Rio de

la Plata. Passengers are sprayed with phenol and Labarraque's

solution and left to dry on aromatic plants and disinfectants.

Prisoners in shackles and those with death sentences open letters

from Brazil and show them to their addressees from a distance.

When a northern wind blows, alarm bells ring so inhabitants can run

for cover. They jump over bonfires to purify themselves of miasmas

(Revista Illustrada, 1889, year 8, n.362, p.4-5. Arquivo Geral da

Cidade do Rio de Janeiro).

Campinas was site of the largest number of vaccinations: 651. This was because the public health crisis there was quite serious and the city lacked efficient resources for treating victims, but most certainly also because of the support Freire enjoyed among the city's republicans and liberals. He was there with Clemente Ferreira and Azevedo Correa, the physicians on the commission sent by the Imprensa Fluminense. Records in fact indicate that republicans held a banquet in the physicians’ honor in June 1889. At the height of the epidemic, vaccinations were performed by Soares da Camara, a pharmacist assigned by the central government, and mostly by Dr. Angelo Simões (1860-1907), clinical director of Santa Casa de Misericórdia and a physician at Benificiência Portuguesa Hospital; in the opinion of Santos Filho and Novaes (p.81-2), he was a “preeminent figure” in Campinas medicine in the 1880s. Simões was to stand among the most faithful followers of Freire. His data supporting the vaccine were endorsed by the president of the Chamber, the police commissioner, a priest, a canon, the director of the newspaper Correio de Campinas, and the editors of the Gazeta

de Campinas 40 and Diário de Campinas.

GEOGRAPHIC DISTRIBUITION OF INOCULATIONS BY FREIRE

 

Source: Freire (1896).

From December 1888 through June 1889, when yellow fever spread throughout these rural parts – many affected for the first time – a total of 3,576 people were vaccinated, 988 of whom were immigrants and 2,537, Brazilian (70.94%). Average mortality among those vaccinated was 0.79%, a figure that fell to zero in Santos, Resende, Serraria, and Cataguases. “Given these clear successes … who would dare to doubt the efficaciousness of our prophylactic measure and the truth of the fruitful doctrines formulated by our eminent master, Pasteur?” asked Freire (op. cit., p.22, 25).

The more the urban middle layers accepted his new invention, the more he was vulnerable to criticism from his adversaries, since the statistical gap was widening between the vaccinated population – native-born, blacks, and immigrants considered ‘acclimated’ and thus immune to yellow fever -and the population still susceptible to the disease, made up mostly of recent immigrants. Changes in the social composition of those vaccinated reflect changes in how the vaccine was distributed. During an era of heightening skepticism not only about yellow fever remedies but also about the feasibility of sanitizing the Brazilian capital, this biological product became a most welcome component of the doctor/patient relationship and of relations between philanthropical institutions and the needy.

There is no way of knowing Adolpho Lutz's opinion of Freire's vaccine. It is certain that he witnessed its use in Campinas, and all indications are that he began analyzing the question, with his typical painstaking rigor, in an unsigned article attributed to him by the organizers of his archive, his children Bertha and Gualter Adolpho Lutz. “On the question of the efficaciousness of vaccination against yellow fever” [in Port.] would appear to be the first article in a series, but we were unable to locate any subsequent editions of the periodical in which it was published and therefore unable to ascertain whether Lutz continued the analysis initiated in São Paulo on 11 May 1889.

The article came out in the Freie Presse: Zeitung für Deutsche in Brasilien, a periodical founded that same year and put out three times a week. It had representatives not only in Campinas (Guilherme Trippe, resident and/or with a business at 99 Lusitana Street) but in nine other cities in São Paulo too (Araras, Botucatu, Piracicaba, Pirassununga, Ribeirão Preto, Rio Claro, Santos, São Carlos do Pinhal, and Sorocaba), as well as Curitiba, Joinville, and

Leipzig, home to Germany's major publishing houses.41

In 1889, Freire and his allies endeavored to convince the central government to back generalized used of the vaccine. On several occasions, in an effort to lend legitimacy to a final test on the entire population, allusion was made to the resolution approved in

Washington. 42 Vaccination was pushed heavily by the abolitionist and republican movements, its organized groups, and its broad network of supporters. The backing of Rio's Society of Medicine and Surgery did not reflect the authorities’ favorable acceptance of the vaccine so much as doctors’ adoption of it in their contact with patients.

The Proclamation of the Republic in November of that year coincided with the outbreak of another yellow fever epidemic, and during the new government's negotiations over the federalization of health services, the vaccine issue led to creation of a new governmental

institution: the Domingos Freire Bacteriological Institute. 43

The microorganism attenuated by Freire was, however, not the only one incriminated as a yellow fever agent. The transition from monarchy to republic actually coincided with a transition between two cycles of theories about the etiology of the disease, a transition not limited to Brazil and in no way related to the processes leading up to a regime change there. Nevertheless, the bacteriological institutes that came to life in Rio de Janeiro and in São Paulo during the early years of the new regime were to take stands on opposite sides of this issue.

Manoel Carmona y Valle, a Mexican, was one of the Brazilian bacteriologist's opponents; using a fungus he found in sick people's urine, he developed a vaccine that was put to wide use in his native

country. 44 In Cuba, Carlos Juan Finlay used mosquitoes infected by yellow fever sufferers as live immunizers against the disease; he suggested an alternative to Freire's alga: the Micrococcus

tetragenus.45

In Brazil, Freire's chief opponent was João Batista de Lacerda, who served as director of the Museu Nacional in Rio de Janeiro from

1895 through 1915. 46 In 1883, when Freire was finalizing preparation of the vaccine, Lacerda incriminated Fungus febris flavae as the true yellow fever agent. The latter microorganism and other, similar ones then described had one characteristic in common: polymorphism, that is, the ability to change shape and function in response to their environment, above all to climatological factors. Zoologists,

botanists, and bacteriologists had differing opinions on the matter.47 Pasteur and Koch felt that polymorphism occured only in the absence of rigorous experimental procedures and was incompatible with the notion of etiological specificity (to put it simpler, with the notion that one single microorganism could be the agent of each disease), but many investigators recognized this property in the fungi, algae, and bacteria they were studying. The issue had to do with the still problematic classification of these “infinitesimal” entities. The generic term ‘microbe’ had in fact just been coined, precisely with the purpose of addressing the confusing taxonomic categories then being used in scientific texts, which complicated discussions of germ theory among non-specialists, including physicians and hygienists (Benchimol, 1999, p.191-200).

Polymorphism was the cement Lacerda used when drawing up his most comprehensive theory on “The pathogenic microbe of yellow fever” [in Port.], read before the National Academy of Medicine and the Panamerican Medical Congress in 1892-93. All descriptions presented up until then only accounted for different phases or forms of an extremely protean fungus.

The cycle of discoveries of these microplants began to ebb when a number of microbe hunters were converted to the hypothesis apparently formulated by Robert Koch that yellow fever was produced by a bacillus similar to the cholera bacillus, discovered by him in 1883 in Egypt and in India. His reasoning was that the prime symptom of yellow fever – so-called black vomit – was also located in the intestine.

 

João Batista de Lacerda in the physiological laboratory at the

National Museum, in 1902 (Acervo Iconográfico, Museu

Nacional/UFRJ).

At the same time that Lacerda was defending the ever-morphing fungus, George Sternberg, chairman of the American Public Health Association and Surgeon General of the United States, was conducting refutative fieldwork and laboratory research into the theories and vaccines then in fashion in the Americas (United States Marine Hospital Service, 1890). He was also searching for evidence in support of a microorganism similar to the Vibrio comma. He wiped the slate clean in a field then pervaded by fungi and algae, opening the way for bacilli to compete in the 1890s for a place as the

causative agent of yellow fever.48

The Pasteur Institute, which had been prudently holding back, corroborated the U.S. investigation (Annales de l'Institut Pasteur, no. 4, 25 Apr. 1890, p.253), and a large part of the international scientific community saw this as proof that the South Americans had failed in their attempts to isolate the microbe and produce an efficacious vaccine. Yet other sources show that Sternberg was so inept in conducting his research in Rio de Janeiro that he helped strengthen Freire's prestige among Brazilian nationalists, positivists, and republicans.

One of the microbe hunters trying to prove Koch's hypothesis was Felix Le Dantec. A physician with the French navy, he had been in Cayenne in 1887 during an epidemic of vomito. The culture from this organic liquid provided him with three varieties of bacilli, which he rediscovered in stomach mucous and in the large intestine. So he raised the question: “Is yellow fever a microbial disease located in the stomach? Are these stomach microbes merely by-products?” Le Dantec knew he had not complied with Koch's postulates for proving a causal relation between the microbial agent and the disease, so he limited himself to affirming “the substantial role played by the digestive tract in the evolution of yellow fever” and to declaring that this in itself afforded “valuable indications regarding treatment” (cited in Bérenger-Féraud, 1890, p.733).

On 15 December 1892, Le Dantec took office as director of the Bacteriological Institute of São Paulo, one of the divisions of the state's Sanitation Service inaugurated six months earlier. His name had been suggested by Pasteur himself, through the French scientist Henrique Gorceix, director of the Ouro Preto School of Mines. Le Dantec promised to implement an ambitious program inaugurating bacteriology in São Paulo; however, less than a year later (5 Apr. 1893), he returned to Europe “without having done anything” -Cesário Mota Junior, secretary of the interior, observed caustically – “other than making some preparations on the topic of yellow fever, which he took with him when he went, leaving the impression that

this was his only intention in coming to Brazil” (Lemos, p.16-9). 49

Felix Alexander Le Dantec, in a drawing by Alicia Büller Souto

 

(Museu Emílio Ribas).

When Le Dantec returned to France, Adolpho Lutz, appointed under-director on 18 March 1893, took charge of the small team comprising three aids and two helpers who were to assist him in tackling some demanding missions:

the study of microscopy and bacteriology in general and,

particularly, as regards the etiology of the state's most common

epidemics, endemic diseases, and epizooties; the preparation

and packaging of the products needed for preventive

vaccination and any therapeutic applications that may be

indicated; the microscopic examinations needed to clarify

clinical diagnoses. (Lemos, 1954, p.16)

Sworn into office only on 18 September 1895, Lutz remained in this position for 15 years, until transferring to the Oswaldo Cruz Institute in November 1908. With the aid of his assistants, he carried out valuable research on the infectious diseases that were endemic to the state or erupted in the form of epidemics. He also faced harsh opposition from a majority of those within the medical field and from other social actors.

Yellow fever was one of his topics of study, guided by the conviction that the causative organism would “quite likely” be found in the digestive tract.

At first Lutz followed in his predecessor's footsteps. Histological and bacteriological research from 1893, which had used material collected during the autopsies of five yellow fever victims, led him several times to “a bacillus of the gastrointestinal tract, which [seemed] to be the one that Le Dantec isolated earlier from black vomit in this same laboratory.” Lutz and his aids found very similar types in the stomachs and intestines of corpses; they cultured these organisms and analyzed them at length in an attempt to differentiate them. As director of the Bacteriological Institute, Lutz wrote:

 

São Paulo Bacteriological Institute at the beginning of the 20th

century (Coleção Secretaria da Agricultura Comércio e Obras

Públicas do Estado de São Paulo, Centro de Memória, Unicamp).

We can state that so far Le Dantec's bacillus has not been found

except in cases of yellow fever. But only another epidemic of

this ailment can provide us with enough material to clarify this

important question once and for all.50

In early 1894, 51 the Isolation Hospital in the capital of São Paulo admitted a number of cases, mostly from Rio de Janeiro, Santos, and Porto Ferreira. Autopsies were performed on eight corpses from São Paulo, one from Belém do Descalvado, and another from Santos.

The examination of tissue slices from the viscera of these corpses and also of sick people's vomit and feces almost always produced negative results. Lutz gave no importance to the bacteria found, assuming they had invaded the tissue after death. Numerous cultures were made with blood from the viscera and with the contents of the stomach and intestines, but no germ new to science was detected. Lutz in fact concluded that Le Dantec's bacillus – always absent – was “introduced via certain food (milk?) or medication.” Colonies similar to Bacterium coli commune were isolated on several occasions.

 

São Paulo Isolation Hospital. Observation Ward seen from the side

(Algumas instalações do Serviço Sanitário de São Paulo. São Paulo:

Vanorden, 1905. Museu Emílio Ribas).

Because there were not enough sick people in São Paulo, studies only proceeded in February 1895, at the Isolation Hospital in Santos, where Arthur Vieira de Mendonça stayed for ten days and Lutz,

five. 52 There they could observe people just coming down with the disease and could culture material from the organs of those who perished.

They once again failed to find any “constantly present” parasite either through direct microscopic examination or after subjecting preparations and histological slices to known staining processes, as well as to some recently discovered ones, “used for the first time to study yellow fever.” Inoculated into a number of culture media, the blood most often would remain sterile for over fifteen days. “On rare occasions, varieties of white or yellow sarcines would develop, which can be considered accidental contaminations.” Cultures made from the blood of yellow fever sufferers in the final stage of the disease would at times produce microorganisms resembling Bacillus coli communis and also streptococci and other varieties of cocci “not yet determined.”

In tissue slices from the stomach and intestinal walls and also in the mucous membrane of the duodenum and the ileus, “a large number of bacilli [were often verified to be] invading the epithelium (which displayed a greater or lesser degree of necrosis) and not rarely the submucous membrane as well.” These were mainly the Bacillus mesentericus vulgatus, Bacillus subtilis, and Bacillus albuminis.” The scientists concluded that this constituted a

post mortem invasion by common species whose resistant

spores are always present in the stomach and that develop

chiefly where the mucous membrane suffers peptic softening …

We have encountered similar processes in illnesses that differ

entirely from yellow fever.

In his February 1895 report, Adolpho Lutz stated that he still thought it likely that the yellow fever agent resided in the digestive tract, like the cholera agent, but so far he had failed to isolate any organism different from those found in other diseases.

We paid the price of much thankless work to obtain these

results, most negative, in perfect agreement with Sternberg's. It

is our opinion that the yellow fever problem not only still awaits

solution but will prove quite challenging … Either its germ is so

poorly characterized that it blends in with common germs, or it

can only be found in significant abundance during a very limited

time period, or, lastly, we as yet lack any method for recognizing

and culturing it.

In 1897, the incidence of yellow fever dropped off in the state of São Paulo, with only forty-one patients admitted to the Isolation Hospital during the first five months of the year. Lutz and his aids autopsied seven of the twenty-eight people who died there; they came from Rio Claro (three), Dois Córregos (two), Araraquara (one), and Leme (one). Another five cases were cured and provided material for bacteriological examinations of the contents of the stomach and intestines, and also of the bile, urine, spleen, blood, and other organic liquids (Lutz, 1898).

The results were as frustrating as before.

 

Sanarelli's bacillus on the agenda

On the façade of the Domingos Freire Bacteriological Institute in Rio de Janeiro waved a tri-color flag, black symbolizing vomit; yellow, jaundice; and red, hemorrhaging. This emblem brought home the image of a bulwark erected to defend a discovery coveted by so many. The flag was hoisted at the moment when the press was stirring up expectations that yellow fever's secrets were about to be revealed by Giuseppe Sanarelli, a renowned bacteriologist hired by the Uruguayan government to establish and direct the Institute of Experimental Hygiene, inaugurated in Montevideo on 16 March 1896. Sanarelli, 31, had previously worked in Camilo Golgi's laboratory at the University of Pavia, at Max von Pettenkofer's lab in Munich, and at Elie Metchnikoff's lab at the Pasteur Institute, in Paris. There he had conducted studies on immunity in typhoid fever and cholera, earning himself a respected name within the international scientific community (Brazil-Medico, no. 24, Jun. 1896, p.218).

Three months after inauguration of the Montevideo institute, the Italian bacteriologist came to Rio de Janeiro in quest of the organic matter he needed in order to study yellow fever. In January 1897, his caldron was bubbling. In the salons and cafes of the Brazilian capital, the topic of the day was the news that Sanarelli had completed his research and had sent a pli-cacheté (sealed communication) to the Academy of Medicine in Rome to guarantee his place as the first discoverer. From the time he took this initiative until the discovery was finally disclosed (postponed more than once), a number of other postulants to the title of discoverer of the cause and/or cure of yellow fever made their way onto the public stage.

General view of Montevideo from the mountains. Drawing by Taylor,

based on a photograph (Reclus, 1894, p.567).

Wolf Havelburg announced his partial results at a conference on 22 April 1897, at Rio's Leprosy Hospital (which, it should be mentioned, had one of the best-equipped bacteriological laboratories in the city). The bacillus he found in the stomachs and intestines of people suffering from yellow fever had produced a typical disease when inoculated in rabbits and guinea pigs. After he injected the blood of convalescing patients into these animals, they displayed resistance to subsequent injection with the deadly culture, proving the feasibility

of serum therapy. 53 Havelburg's conference (1897) was attended by representatives from all of Rio's medical institutions and by government figures, journalists, and other gentlemen likewise interested in keeping abreast of advances in science, which at that point were overwhelmingly complex. The event sparked further research into yellow fever.

Eduardo Chapot Prévost (26 Jan. 1897, Recortes/COC) decided to break the silence he had been keeping; he had been reluctant to release information on studies he deemed “not sufficiently corroborated to warrant publication, especially in regards to such a knotty, controversial, difficult matter.” He had conducted his investigations in collaboration with Francisco Fajardo,

either passing whole days at São Sebastião Hospital performing

autopsies or chemical and microscopic examinations of blood,

vomit, urine, and feces; making cultures of liquids, humors, and

fragments of organs in different media, in plates and in tubes …

or accompanying the march of the illness at the patients bedside

… or spending night after night, until two or three in the morning,

studying under the microscope preparations readied during the

day.

Prévost and Fajardo also verified the constant presence of a bacillus, isolated it in pure culture, and inoculated it into guinea pigs, dogs, and chickens that displayed lesions analogous to those of human yellow fever when they died.

Another to disclose incomplete studies, in March 1897, was Johannes Paulser, assistant at the Bacteriological Institute of São Paulo. In hopes of identifying those germs that appeared on a regular basis, he endeavored to isolate all that he found in the organs of people claimed by the epidemic which had swept through the state in the summer of 1895-96. He eventually incriminated one species of mold and two species of yeast; these had thrived in his cultures and had been found in the twenty-five corpses he autopsied with the help of Arthur Vieira de Mendonça (Jornal do Commercio, 8 Mar. 1897; Brazil-Medico, Mar. 1897, p.78-86). Paulser's mold gave João Batista de Lacerda the opportunity to put back in circulation the question of the polymorphous fungus that he had presented before the National Academy of Medicine and the Panamerican Medical Congress in 1892-93 (Jornal do Commercio, 10 Mar. 1897). Adolpho Lutz dismissed Paulser two months before he released his findings to the press. “Indeed,” wrote O Paiz (18 Mar. 1897), “Dr. Paulser's work had made a poor impression on the group of physicians devoted to bacteriology in Rio, and hence we now rejoice to see him

removed from under the responsibility of Lutz's brilliant name.”54

 

Dr. Eduardo Chabot Prévost (18641907), the Brazilian physician who

became famous for separating twins, Maria and Rosalina, who had

been born joined at the sternum (Acervo COC, DAD, FOC [P],

Chapot-Prévost, E-1).

We now know that this note was written by Fajardo, who on the same date sent the page from O Paiz to his “Friend and Master … with the place of publication marked in blue.” And he inquired: “Could

you please tell me whether you agree? 55 In this same letter, the bacteriologist from Rio informs Lutz that he had received news from Sanarelli: “He is going to make his announcement next May; he is decisive about the microbe. If I had time, I'd go to Montevideo before then.”

In January 1897, the press in Rio de Janeiro started raising the issue. One journalist expressed his “serious anxiousness” to learn the results already achieved by the “wise man from the state of Rio” (11 Jan. 1897, Recortes/COC). But, the journalist went on to state, Lutz was a most cautious investigator and was certainly the most averse to publicity.

One indicator of how seriously yellow fever was taken at the institute headed by Lutz are the data on post-mortem examinations: from 1893 to 1908, the lab's bacteriologists cut open 121 corpses of yellow fever victims and 92 of typhoid fever victims (cholera morbus ranked third, at 62). The figures are even more impressive when we focus only on the 1894-97 period: 86 autopsies performed on victims of yellow fever and 67 on those who died of typhoid fever. In 1896, 43 victims of the first disease were autopsied and only 18 of the

second.56

In a mid-1897 communiqué addressed solely to the director of the São Paulo Sanitation Service, Lutz took stock of his studies on the etiology of yellow fever. He had not found any germ that could be incriminated either in the organs of those who had perished from well-characterized yellow fever or in blood drawn during life.

The few positive results can be perfectly well accounted for by

the possible invasion of secondary-infection germs or by the

commencement of corpse decomposition … The cultures that

have been made independently by our laboratory staff from

many autopsies of yellow fever victims have revealed forms that

correspond to species known to produce secondary infections in

other illnesses (as, for example, typhoid fever), mainly microbes

similar or identical to Bacillus coli commune and to pyogenic

cocci. (Lutz, 1897)

Lutz steered clear of any discussion of “certain work undertaken using defective methods and also in the absence of information considered indispensable.” Instead, he limited himself to observing that “the supposed positive results alleged in these works have not been verified by other investigators.” In an article published in the Revista Médica de São Paulo, he expressed the opinion that the bacillus described by Havelburg appeared to be merely “one of the countless varieties of Bacillus coli communis, which, as we have verified, is often quite virulent for animals, when isolated from cases of yellow fever” (Lutz, 1898).

In a report written earlier,57 Lutz had pointed out that the anatomical lesions observed in the viscera by advocates of the etiological theories then in circulation had been “quite exaggerated, since the authors had examined poorly conserved specimens or ones removed from the corpse long after death. Thus, changes owing to decomposition, which occurs very rapidly in yellow fever, were grouped together with changes caused by the illness.” In kidneys suffering such conditions, Lutz always saw “coagula of albumin and cylinders in the lumen of the renal tracts, but in well-preserved specimens the epithelia [were] all in their proper place, and the nuclei [were] easily stained.” The same thing was the case with the liver: “the cells always contain many yellow pigment granules; using certain staining methods, these hold the color of the dye, but only a careless observer could confuse them with microorganisms.” Clinical observation showed that the viscera quickly resumed their functions once the critical phase of the disease had passed, which seemed to demonstrate that the lesions weren't very deep: “everything indicates that this is caused by intoxication by toxins rather than the localization of the infectious process inside the parenchyma of the viscera.”

This line of anatomical-pathological investigation led Adolpho Lutz to provide guidance to one of his assistants, Dr. José Martins Bonilha de Toledo, who was studying urine in yellow fever. Bonilha de Toledo, who had specialized in biological chemistry in Belgium, conducted in-depth chemical and microscopic analyses of the urine of thirteen victims of the disease. He concluded that renal lesions were a constant, and directly proportional to the seriousness of the case, confirming the suspicion that they were caused by a toxin secreted by the unknown microbe responsible for producing yellow fever. In January 1897, Bonilha de Toledo published his observations on renal changes and on variations in the chlorides, phosphates, and urea of yellow fever sufferers’ urine. He left only a few clues when it came to solving the etiological question, but he clarified some still

obscure points concerning diagnosis and prognosis of the disease. 58

Adolpho Lutz, the “wise man from the state of Rio,” boasted credentials as solid as those of Giuseppe Sanarelli, the “wise Italian.” Thanks to Lutz's circumspection and prudence, and also to the capacity of the laboratory he headed – superior to those operating in Rio – he distinguished himself as the foremost “verifier” of the microbes, sera, and vaccines proposed by these zealously competing bacteriologists. Above all, was someone who sought victory by following the most unusual pathways, going farther than all others in his handling of the press, in his pursuit of economic advantages, and in mobilizing remarkably strong allies throughout his period in the spotlight.

On 11 November 1896, Felipe Pereira Caldas, a physician from the state of Rio Grande do Sul, spoke before the National Academy of Medicine about the smallpox serum he had developed (Brazil-Medico, Nov. 1896). The newspapers that day made much ado about the news (denied) that Sanarelli had just unveiled the secret of yellow fever. Days earlier, imitating the Italian's action, Caldas had presented the Academy with a sealed communiqué in order to guarantee priority in the discovery of a serum against yellow fever. In January 1897, when Havelburg added fuel to the race to discover the yellow fever microbe, Carlos Seidl tested the first doses of Caldas’ serum at São Sebastião Hospital in Caju, which he directed. The Rio Grande do Sul lobby, led by Dr. Severo Macedo, beseeched Manuel Victorino Pereira, vice-president of the Republic and a physician from Bahia, to sponsor Caldas on a new trip to Rio de Janeiro, arguing that it was essential for a Brazilian scientist to assert priority for the discovery.

Felipe Caldas and his prophylactic reached the height of fame in mid-1897, precisely when Giuseppe Sanarelli, in Montevideo, announced discovery of the icteroid bacillus and the continuation of his efforts to obtain a curative serum. In a message read on 26 June, Brazilian President Prudente de Morais informed the National Congress that the Academy of Medicine, by a unanimous vote, had requested that the government submit Caldas’ serum to large-scale testing in the capital of the Republic and in other places during the next yellow fever epidemic (Diário Oficial, 1 Jul. 1897; Brazil-Medico, 1 May 1898, p.145). The message was accompanied by a statement from Nuno de Andrade, director of Public Health, in which he declared that

Dr. Caldas’ yellow fever serum is not the fantasy of a visionary

discoverer, but a medicine that can easily become part of yellow

fever therapy, and whose full benefits can only be definitively

measured once its usefulness has been verified in a

considerable number of cases.

In August 1897, Adolpho Lutz, Arthur Mendonça, and Bonilha de Toledo signed a scathing report on Caldas’ findings. Conducted solely in the laboratory, the verification contrasted sharply with the results of clinical studies by physicians from Rio. Lutz placed quotation marks around phrases used by Caldas, to underscore questionable aspects of both method and product: the serum's supposed dual-purpose nature (preventive and curative); the possible contamination of material collected in Rio de Janeiro and transported to the city of Rio Grande; and the non-determination of the microbe correlated to yellow fever.

Asked if he used one of the known methods for isolating the

germ, he answered in the negative, since he ‘only had liquid

serum available, in which — in his opinion — the only germs

born are yellow fever ones.’ Asked if the inoculated animals

displayed yellow fever symptoms, he said no. (Lutz and Toledo,

1897)

Although this report by the Adolpho Lutz team did not eliminate the discovery made in Rio Grande do Sul (it would find a place in newspaper headlines on and off until 1902), it did clear the way for a more enthusiastic acceptance of the discovery of the icteroid bacillus announced by Giuseppe Sanarelli on 10 June 1897, at Montevideo's Teatro Solis.

Adolpho Lutz and Arthur Vieira de Mendonça traveled to Uruguay's capital in June as delegates of the São Paulo government. They were soon joined by João Batista de Lacerda, Brazilian government representative, along with Francisco Fajardo, Chapot Prévost, and Virgílio Ottoni, delegates for Rio's Society of Medicine and Surgery

and for the Union of Hospital Interns. 59

A parenthetical comment: On his way back to Brazil, Lutz stopped in Buenos Aires to meet the pathologist Robert Johann Wernicke (1854-1922) and his disciple Alejandro Posadas (1870-1902). There he closely examined the microscopic preparations and clinical cases that had prompted Wernicke to publish a special communication in the Centralblatt für Bakteriologie und Parasitenkunde (v.12, p.859-61, 1892) under the title “Ueber einen Protozoenbefund bei mycosis fungoides,” and Posadas to publish “Un nuevo caso de micose fungoidea con psorospermia” in the Circulo Médico Argentino (v.15, p.585-97, 1892). Lutz's visit was spurred by his studies then underway in São Paulo, which were to culminate in his 1908 publication of a paper that would eventually be recognized as his chief contribution to Brazilian dermatology: the discovery in Brazil, for the first time, of a disease characterized by serious mouth lesions, today known by a variety of names, including Lutz disease

or Lutz mycosis.60

In Montevideo, Lutz attended a conference that Sanarelli held for “a mixed public of professionals and the lay.” The audience included the president of the Republic, the upper echelon of government administration, and Uruguays high society, along with medical

delegations from a number of American countries.61 Lutz made several visits to the Italian bacteriologist's laboratory to collect supplementary technical information on the facts he had announced. In Lutz's August 1897 report to the director of the São Paulo Sanitation Service (1897a), he stated that these facts could not be negated “save on the basis of other observations and, in the absence of these, they should be accepted on the author's guarantee. His capacity and skill have been proven by his earlier

works, and I have had ample opportunity to verify them personally.” 62

Sanarelli had confirmed the frequency of the secondary infections verified by Lutz. “He even assigns a more important role to them in this disease's high mortality rate than would to us appear justified based on anatomical and clinical observations” (Lutz, 1897a).

 

From left to right, Dr. José Sanarelli, Dr. José Cobria and Dr. Juan

Morelli (Institute of Hygiene of the Faculty of Medicine of the

Universidad de la República, Montevideo, Uruguay).

The Italian scientist had isolated his bacillus from blood drawn from the organs of corpses of yellow fever victims, which for Lutz had always yielded negative results. The latter accounted for this as follows: it was so hard to find the germ that Sanarelli had only managed to isolate it in half the examined cases, “a very unfavorable proportion when compared to other microbial illnesses” (Brazil-Medico, 15 Dec. 1898, p.416-7). Having a “common” form, it could not be differentiated from the abdominal typhus bacilli or Bacillus coli communis. Under normal conditions, it did not even produce colonies on gel plates and therefore investigations using this culture (considered the best means for differentiating microbial species) had all met with failure. Furthermore, the presence of other bacteria hindered the development of the bacillus incriminated by Sanarelli: “The author himself deems it quite fortunate that he found it in almost pure culture in the second case he observed. He also feels that isolation of this germ is still very difficult today and, in certain cases, even impossible” (Lutz, 1897a).

Since there was so little to characterize it, he would not have noticed it “were it not for his extensive and truly colossal study of the pathogenic action of all the bacteria then isolated” (Brazil-Medico, 15 Dec. 1898, p.416-7).

In compliance with Koch's postulates, Sanarelli had verified the pathogenic action of the icteroid bacillus in a number of mammal species. He had managed to induce

morbid processes typical for each species, but different from

each other. These processes reproduce … part of the

phenomena observed in man when stricken with yellow fever.

We watched a certain number of these experiments and saw

anatomical parts from the cadavers of others; we thus had an

opportunity to verify the exactitude of Sanarelli's descriptions in

various regards, and, as the other facts were witnessed by

qualified people, they can be deemed established. (Lutz, 1897a)

In Lutz's opinion, the probability that this bacillus was the cause of yellow fever had become a certainty following five experiments on human beings.

I cannot speak from personal observation, but the doctors who

have had an opportunity to observe them recognize the

symptoms typical of yellow fever. The temperature curves for

these cases certainly correspond in every way to those of

spontaneous yellow fever. Moreover, in Montevideo not one

single voice has been raised to question these experiments,

which have been deemed fully corroborative and decisive. (Lutz,

1897a)

On 22 July 1897, the delegates from Rio de Janeiro stepped up to the podium before the National Academy of Medicine to report on this discovery to an “especially” large audience, comprising physicians, students, and spectators from “various social classes” (Brazil-Medico, Aug. 1897, p.283-5). Lacerda spoke of the Uruguayans’ pride in the Institute of Hygiene, “unrivaled in South America.” He described the research studies that had led to the isolation of an extremely virulent bacillus and the subsequent inoculation experiments, conducted in an order of increasing zoological complexity: rodents, ruminants, simians, and, lastly, human beings. In closing, he reported on the counter-evidence he had obtained at the laboratory of the General Directorship of Public Hygiene, with the help of Dr. Emilio Gomes and the assistance of Chapot Prévost, Affonso Ramos, Zacharias Franco, and Antonio Pimentel. At the same session of the Academy and some days later at the Society of Medicine and Surgery, Francisco Fajardo presented equally positive results on the inoculations he had conducted with