Chagas Disease: History of a Continent's Scourge 9780823291137

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Chagas Disease

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Chagas Disease History of a Continent’s Scourge

François Delaporte Translated by Arthur Goldhammer

fordham university press n e w yo r k

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2012

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Copyright © 2012 Fordham University Press All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means—electronic, mechanical, photocopy, recording, or any other—except for brief quotations in printed reviews, without the prior permission of the publisher. This work was originally published in French as François Delaporte, La maladie de Chagas © 1999 Editions Payot & Rivages. Cet ouvrage a bénéficié du soutien des Programmes d’aide à la publication de l’Institut Français. This work, published as part of a program of aid for publication, received support from the Institut Français. Fordham University Press is grateful to the Université de Picardie Jules Verne for the subvention that made possible the translation and publication of this book. Fordham University Press has no responsibility for the persistence or accuracy of URLs for external or third-party Internet websites referred to in this publication and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Fordham University Press also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Library of Congress Cataloging-in-Publication Data Delaporte, François, 1941– [La maladie de Chagas. English.] Chagas disease : history of a continent’s scourge / François Delaporte ; translated by Arthur Goldhammer. — 1st ed. p. ; cm. — (Forms of living) Originally published: La maladie de Chagas. Paris : Editions Payot & Rivages, 1999. Includes bibliographical references and index. ISBN 978-0-8232-4249-8 (cloth : alk. paper) — ISBN 978-0-8232-4250-4 (pbk. : alk. paper) I. Title. II. Series: Forms of living. [DNLM: 1. Chagas, Carlos, 1879–1934. 2. Chagas Disease—history— Brazil. 3. History, 20th Century—Brazil. 4. Parasitology—history— Brazil. 5. Trypanosoma cruzi—pathogenicity—Brazil. WC 705] 614.5'330981—dc23 2012009228 Printed in the United States of America 14 13 12

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First edition

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contents

Foreword by Todd Meyers

ix

Introduction

1

1.

Identifications

10

2.

System

47

3.

Revisions

73

4.

Recasting

103

Conclusion

133

Notes

139

Bibliography

153

Index

177

vii

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foreword: the false cannot be the moment of the true Todd Meyers

“The false cannot be the moment of the true.”1 In one sentence François Delaporte summarizes the history of Chagas disease (American trypanosomiasis) and simultaneously challenges the ground of that history’s making. The force of the sentence first requires some understanding of the context of the problem. In part, such a statement is Delaporte’s response to the conventional narrative offered as the history of the discovery of American trypanosomiasis, which goes something like this: A young Brazilian scientist is sent to a small village to help with a disease outbreak hindering the construction of a railroad. While there, he identifies a flagellate protozoan, Trypanosoma cruzi, carried in the belly of the vinchuca bug and transmitted to humans through the bug’s bite. Carlos Chagas’s description in 1909 becomes the moment of conception for a disease and the birth of subsequent narratives of scientific and nationalist progress. Even within the historiography of Chagas disease, replete with its detours, arguments, and debates, the moment of discovery remains intact.2 But as François Delaporte suggests, if Chagas’s description is the moment, it is a moment signifying equal parts fiction, invention, and confusion. Strictly speaking, such a history is a refusal of its object. In Chagas’s description we find the absence of a nosological entity, the conflation of American trypanosomiasis with other endemic conditions, and the inability to clinically specify the disease. It is not until 1935 that Cecilio Romaña identifies the clinically recognizable and discrete entity known as American trypanosomiasis. The unilateral, painless orbital edema (the swelling of the eyelids) that would become known as “Romaña’s sign” was simple to identify and highly correlated with the presence of the disease.3 So why does Romaña’s clinical description introduce a question of ix

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Foreword

the false? The problem, on one hand, is the insistence on practices of naming—strange in a case where a signifier is no longer found to be the container for the signified. On the other hand, and perhaps more to the heart of the matter, the history of Chagas disease requires an epistemological reconfiguration in the understanding of the science of a disease at the intersection of its objects and thought. Said another way, there was no science of Chagas disease until 1935 because the thing that Chagas described was not American trypanosomiasis but rather a disease (or many diseases) without systematic articulation. The question of the false should not be mistaken for the productive power of “error” in the sense that Georges Canguilhem describes, though in this case Canguilhem’s words prove telling, if not a little cautionary: “While errors in judgment are accidental, alteration is the essence of memory.”4 How can the story of a disease that occurs primarily in rural areas of Latin America offer such fertile ground for debate about the making of the history of science and the history of thought more generally? First, Delaporte’s essay is about the methods and modalities of history, not only a history. Although its singularity is located in the subject of American trypanosomiasis, the materials that define the subject continually open onto and secure new objects and ideas. Second, the essay does not offer simply an alternative or competing story of discovery. The point is easily lost. After 1935 even Chagas himself would readily refer to Romaña’s sign as the defining clinical manifestation of the disease. If anything, we begin to see the asymmetries of thought that the custodians of a particular vision of the past offered as fact—fact made from many fictions.5 Romaña discovered a symptom that did not revise an understanding of a disease’s pathology; he drew together the very elements of the disease itself. The epistemological turn in the story of Chagas disease will be found in the pages that follow. And, indeed, for the careful reader the value of a historical project writ large will become apparent. With what I’ve described in mind, I will end by borrowing a quote from Gaston Bachelard, cited by Georges Canguilhem in his essay on the role of epistemology in the history of science: “Every historian of science is necessarily a historiographer of truth. The events of science are linked together in a steadily growing truth. . . . At various moments in the history of thought the past of thought and experience can been seen in a new light.”6

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Introduction

In 1923, Souza Araujo described living conditions in northern Brazil as follows: Tampac has sixty or so cottages whose walls and doors are made of boards or logs laid horizontally one on top of another. The construction is identical to that of the homes in Gurupy that I described previously, except that these cabins are much better built. The upper part of the outer walls is covered with thatch. An inner wall divides the house into a common room and a bedroom. The kitchens of the Saramacas are very clean. They own a few items of furniture, some clay pots, and utensils. Passing through the small door that gives access to the two bare-walled rooms of the rancho, one enters a small dormitory with no opening to the outside. The blacks sleep in hammocks, like our natives and half-breeds. The homes of the people who live near the Bragança railroad and around the capital are identically built. The form is the same and the quality of the construction materials scarcely varies. These are authentic state rural homes, here called barracks but known in the south as cafuas (dens). They are enclosed by walls packed with sod. Usually there is a front door and a window. The main room opens onto several bedrooms, usually windowless and poorly ventilated, which contain a number of hammocks. Sometimes there are benches but seldom any other furniture, along with very rudimentary kitchen utensils. These houses are covered with small boards, here called cavaco. They have neither ceilings nor floors. Similar homes are found in the central states. In Minas Gerais and São Paulo, they are veritable nests of “barbeiros” (Triatoma megista). These hide and lay their eggs in the crevices and interstices of the sod-packed walls. Fortunately, there are no “barbeiros” in this state, nor is there any Chagas disease. . . . As for the barracks that are found around and even within the city of Belém, their roofs vary: some are thatch, others made of small boards, and still others of sheets of zinc. . . . In the 1

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Introduction interior it is common to find homes whose walls are decorated with newspapers, photo magazines, and even calendars. These are the only ornaments. . . . In the works published by the Goedli museum, in its magnificent bulletin, one can see that the type of house I have just briefly described is the most prevalent throughout the interior of the state.1

At about the same time, for the commemoration of the hundredth anniversary of Brazil’s independence, Dias offered this description of the Oswaldo Cruz Institute: In strange contrast to the silence that envelops the neighborhood, here, within the magic castle, work and bustle are the rule everywhere. It is a human beehive set in a magnificent palace. From the porch of the building, throbbing with electrical machinery, and the luxurious stables filled with neighing, well-fed animals, to the upper floors alive with intense intellectual activity, everything stands in sharp contrast to the monotony of the surroundings and the placidity of the sea languishing in the salt marshes adjacent to the distant bay. Visitors are dazzled and confused by all this. From a distance they attentively contemplate the splendid building. In their eyes one reads the tranquil pleasure experienced only by souls endowed with natural artistic taste or raised in the refinement of old civilizations. . . . A woman stands out from this distinguished group, walking ahead in search of new emotions. Now she stops, charmed by the architectural details and alert for more. “It’s in the purest Moorish style,” she says with delight. She is a woman of artistic soul. . . . The visit is nearing its end on an upper floor of the building. . . . The daylight is waning. . . . The splendid Brazilian sun swoons in a polychrome orgy, a splendid funeral for the dying day. The setting is truly poignant. The distinguished visitors have finished praising our enchanted nature. Gazing into the distance, they glimpse the beautiful city, palpitating and purified. At their feet lies the great national institute. Sweet dreams realized, in his time, by the same man! . . . Here, despite the perpetual absence of technology, he had the idea of building a monument that stands as one of the architectural wonders of Rio de Janeiro. . . . In this forgotten corner of Manguinhos arose a majestic palace, which is a scientific gem set in a divine aesthetic. Since Oswaldo did nothing without a reason and was ruled by an inflexible logic, we have often pondered his motives for choosing, among many prestigious architectural schools, the often denigrated Moorish style. The master’s architects were consulted, and informed opinions were sought, to no avail. . . . Perhaps the master’s heart was moved by the disdainful injustice with which the promoters of the dominant aesthetic were accustomed to treating Muslim art—so subtle, so whimsical, so passionate, and so seductive to anyone who contemplates it without preconceived

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ideas. . . . Because everything in it is incomparably enchanting. . . . Perhaps, one day, someone came upon him in a state of ecstasy as he visited his palace and could not refrain from questioning him directly: “Why did you choose the Moorish style?” “Because it was the most beautiful,” he answered in the natural tone of one who is accustomed to speaking the unvarnished truth.2

We have before us, then, a palace and a rancho. On the one hand, dominating the bay of Rio de Janeiro, the elegant residence of the scientific elite and center of a medical revolution. And on the other hand, in the arid and inhospitable central states of Brazil, the dwellings of poor, illiterate families, built in the image of the huts of their African and Indian ancestors. The palace was constructed of the noblest and most costly materials, all imported from Europe: the marble and mosaic came from Portugal, the brick from France, and the cement from England. The building began with a sketch by Oswaldo Cruz that was developed by the architect Morais and required the collaboration of numerous trades to complete. By contrast, the rancho was made of the humblest materials: wood, sod, and thatch scavenged from the local environs. No special skills were required. The palace was filled with equipment imported from the United States and Germany, the products of the most advanced technology. The building was richly ornamented: Its walls and ceilings were encrusted with arabesques reminiscent of oriental splendors. The huts of the poor contained only rudimentary utensils and makeshift decorations cobbled together out of old newspapers, photo magazines, and calendars. The contrast between palace and rancho is so striking that it is best not to dwell on it. In any case, my purpose is not to draw attention to the distance between backward Brazil and modern Brazil. In juxtaposing these two descriptions, what I hoped to bring out was the surprising similarity of the concrete historical processes that gave rise to both. I will emphasize the aims of the conquest and the young republic. But I will also insist on what the exploitation of the country’s riches had in common with its socioeconomic transformation. At the time of the conquest, it was essential to ensure that people settled where they worked. At the turn of the nineteenth century, the work force had to be protected. From these facts certain questions arise. What calculations lay behind these constructions? What was expected of them? On what models did they draw? The palace and the rancho define two distinct architectural styles. They sharply inflected the course of history, with unforeseen consequences.

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Introduction

The conquest of Brazil was linked to the exploitation of natural wealth. Mercantile capitalists were at first interested mainly in wood. In the sixteenth century, sugarcane replaced wood as the dominant product of the Brazilian economy. In the eighteenth century, the cycle of diamonds and gold gave its name to the state that lies at the heart of Brazil, Minas Gerais. The mining company in turn promoted agriculture and the production of livestock. In the nineteenth century, coffee, tobacco, and cotton plantations dominated. Labor was needed to cut and transport timber, extract metals, and plant, harvest, and process cash crops. Traders moved in to supply this indispensable manpower. The Portuguese, who controlled the African markets, were the first to supply slaves. They trafficked in blacks along the coast of the Gulf of Guinea, Congo, and Angola. The sugar plantations and mines depended on the influx of Africans. In addition to the trade in blacks, expeditions were sent into the interior of the country to capture and enslave Indians. They complemented the African supply. The slave trade met the needs of planters, merchants, and miners. But cheap labor was not enough. Colonial policy called for settlement of the land. Vast agricultural enterprises achieved high yields by exploiting slaves whose families lived on the master’s plantation. The structure was typically feudal. But the settlement of the land had goals beyond the economic. The conquest also witnessed the creation of missions, which established the first reservations. The king intervened to protect the slaves from the excesses of the colonists. Jesuits organized aldeiras, Indian communities placed under their protection, where Indians could live without fear of brutal treatment by wealthy landowners. The creation of villages, communities, and reservations accompanied the conquest. Establishing settled communities was an innovation, a break with the nomadic ways of the past and the type of dwelling that went with them. Indian tribes had been hunters, gatherers, and fishermen. In the Andes, they had no native animals that could be domesticated. Their communities were mobile. Over the course of the year they migrated from place to place as the seasons dictated, moving to where food was most abundant. The Indians of Brazil moved frequently, whenever the crop of manioc or corn thinned out or game became scarce. Usually they migrated short distances, but sometimes they went farther and invaded the territory of other tribes. No settlement was permanent. The system of slash-and-burn agriculture

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made a semi-nomadic existence inevitable. In the Pampas, tribes moved frequently, setting up tents to use as shelter. Most of the Indians in Brazil lived in temporary villages. The use of wood, vines, and grasses, materials subject to rot, encouraged frequent displacement and rebuilding. Huts of bamboo and straw could be built quickly and covered with roofs of palm leaves. But the advent of settled communities required innovation in building: Wooden structures were now caulked with packed earth. It is tempting to see this minor architectural modification as a result of the importation of traditional African methods: packed earth huts with thatched roofs. But actually it was a matter of architectural syncretism: Traditional Indian structures with sod caulking became the typical ranchos of the colonized regions. There was also a cultural reason for the abandonment of simple wood latticework: Jesuits were shocked by the Indians’ nudity and promiscuity. Filling the interstices in the walls shielded the intimate lives of the natives from view. So little villages sprang up in which each house consisted of wooden latticework covered with packed earth mixed with chopped straw. These crude dwellings had no interior wall covering. In short, this was traditional architecture of wood, thatch, and adobe. The rancho or cafua was the basic rural habitat, a sign of a sedentarized population. The substitution of packed earth for open wood dwellings had an unforeseen consequence. Forest insects could now colonize the rancho. There were good reasons for the biological adaptation of the reduviids, even if it came about by chance. The new dwellings provided the insects with a favorable environment: shelter from predators, light, and a relatively constant temperature that helped them withstand seasonal variations. They could also hide in the crevices of the walls and the thatched roofs to lay their eggs. At night, they could feed on the blood of the inhabitants of the dwelling and their domestic animals. The chroniclers of the conquest were quick to describe the bug that dropped down on its victim at night to suck its blood. As early as the end of the sixteenth century, Lizarraga described “insects that are afraid of the light but come out of the walls when darkness falls or drop from the roof onto the face or head of their sleeping victims. . . . They are clumsy because their legs are long and fine, and after their stomachs fill with the blood they have sucked, they can no longer walk.”3 In the eighteenth century, the Jesuit Gumilla recorded the presence of the bugs in dwellings: “When they

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Introduction

suck blood, they do it so carefully and delicately that the victim cannot feel it. . . . They are common in all temperate places, and it is a serious problem to have them in a newly built house.”4 In the nineteenth century, naturalists followed in the wake of the chroniclers. Darwin wrote: “At night, I experienced an attack (for it deserves no less a name) of the Benchuca, a species of Reduvius, the great black bug of the Pampas. It is most disgusting to feel soft wingless insects, about an inch long, crawling over one’s body. Before sucking they are quite thin, but afterwards they become round and bloated with blood, and in this state are easily crushed.”5 Taxonomic study began with the publication of Carl de Geer’s Mémoires pour servir à l’histoire des insects (1773) and Pierre André Latreille’s Insectes de l’Amérique équinoxiale (1811). In 1850, Stal published his “Monographie der Gattung Conorhinus und Verwandten” in the Berliner Entomologisches Zeitschrift, and in 1872 Walker published his Catalogue of the Species of Hemiptera heteroptera in the Collection of the British Museum. Four centuries after the conquest, the founding of the Republic of Brazil coincided with the accession to power of the coffee oligarchy. The objectives of the new rulers were to develop commerce and industry and create networks of communication. Nascent capitalism required manpower. Measures were introduced to promote worker mobility and hiring. Immigration was also encouraged, and after slavery was abolished, workers were recruited from the local population. But the mere availability of manpower was not enough. The health of the workers also had to be protected: Promoting public health was an instrument of exploitation. The “labor force” had to be preserved and maintained. In 1902, Rodrigues Alves was elected on a reform platform that promised to raise Brazil to the level of the civilized nations. Economic development was linked to immigration and investment: “The capital of the republic cannot continue to be known as an unhealthy place when such powerful forces come together to make it the number one destination for labor, business, and capital in this part of the world.”6 Major projects were often brought to a halt by epidemics that decimated the workers. Yellow fever, bubonic plague, and malaria were permanent dangers. Doctors capable of waging war on sources of disease had to be trained. In the late nineteenth century, the concerns of philanthropists and of the medical elite coincided with those of the government. Brazil embarked on a period of modernization: Public health became a national priority.

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The emergence of disease as an economic and political issue was something new. It marked a break with the medical practice of the imperial era and a change in style for practitioners. At the turn of the century, João VI had imposed European aesthetic norms on Brazil. The French architect Lebreton was supposed to civilize creole society. As a result, most public buildings were built in the neoclassical style. From 1832 (when the faculty of medicine was established in Rio de Janeiro) until the end of the reign of Pedro II, there were debates about the organization of teaching and the practice of medicine. The actions of the Central Health Junta were limited: repression of quackery, inspection of food, and surveillance of public institutions. Interventions directed at the population were rare and limited. Rio de Janeiro was seen as a high-risk port. But the concern with public health led to another innovation. The creation of the Institute of Manguinhos marked a transformation of Brazilian medical science and practice. In a period when Guardia was saying that concern with health had supplanted concern with salvation, Oswaldo Cruz did not need a great deal of imagination to come up with one of the slogans that were his specialty: “Eternal faith in science.” The new institute was to be a center of training, research, and development of new public health standards. In modeling the Manguinhos Institute after the observatory of the Parc Montsouris in Paris, Cruz fastened on the Moorish style as a symbolic expression of spiritual and temporal power. The architecture of Manguinhos stands as a symbol not of science but of the new powers that went along with the practice of Pasteurian medicine. The housing of the new national institute in a Moorish palace had an unanticipated consequence of which Cruz took full advantage. In 1907, Brazil scored a major success at the Universal Hygiene Exposition in Berlin, winning nothing less than a gold medal. The impressive results of the campaign to eradicate yellow fever, following the example of the Americans in Cuba, aroused the interest of German scientists. But the sumptuous model of the institute also proved irresistibly seductive. This had institutional consequences: The architecture of Manguinhos was among the reasons why Schaudinn’s top students went to Brazil. To be sure, the idea of enticing established scientists to come to Brazil was not new. In 1892, Le Dantec had spent time in São Paulo, but instead of giving courses on microbiological technique, he did research on yellow fever. In 1900, Pedro de Affonso’s attempt to recruit Yersin’s assistant,

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Introduction

Charles Carré, ended in failure. Cruz succeeded where his predecessors had failed. The publicity campaign mounted in Berlin with the assistance of Rocha-Lima quickly bore fruit. Cruz was able to arouse the interest and curiosity of foreign scientists and attracted a substantial number of German specialists to Manguinhos. Two of the best experimentalists among Schaudinn’s students were tapped to create and develop the protozoology section. . . . The needs of our medical establishment required us to establish a good school of protozoology, a branch of experimental medicine that would contribute enormously to the understanding of local pathologies. Stanislas von Prowazeck and Max Hartmann accepted Oswaldo Cruz’s invitation to come to our institute, where they offered valuable instruction that left an indelible impression and made the fruits of these fertile minds a part of the finest traditions of Brazilian science.7

Let us recap what we have learned so far. The sedentarization of the population at the time of the conquest was linked to the exploitation of labor. This led to the rancho, a type of dwelling that encouraged the domestication of triatomids from the surrounding woods. By the dawn of the twentieth century, nascent capitalism required the implementation of a nosopolitics. This led to the establishment of the Manguinhos Institute and the introduction of German protozoology in Brazil. The history of science is not strictly speaking concerned with why scientists behave as they do, even though their behavior is part of that history. Cruz came to Berlin from the periphery to seek approval of the new Brazilian scientific center. Conversely, German scientists recognized the Manguinhos Institute as an authentic center of scientific research. Why recount these two histories? Because in the wake of the first, naturalists were able to observe, describe, and classify certain household insects. And in the wake of the second, Brazilian physicians exalted the role of German protozoology in Brazil. Before any research was done on Chagas disease itself, these events created the conditions under which new natural objects were able to emerge, along with new ways of thinking open to the latest experimental techniques. This book will recount the history of the encounter of Brazilian medical science with a certain insect. Around 1910, the identification of flagellated forms in the gut of this hematophage led to the discovery of a pathogenic trypanosome and an associated disease, parasitic thyroiditis. But it was not until 1935 that the ultimate disease entity associated with this pathogen

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appeared: American trypanosomiasis. Clearly, there is nothing automatic about the identification of new pathology: The way in which a morbid entity is recognized depends on the structure of medical perception. In every period there are perceptual thresholds that define the limits of the medical gaze. Rather than focus research on the fruitfulness of Chagas’s medical system, one should rather place the accent on the principles that prescribed the limits of that system in advance. The formation of the concept of parasitic thyroiditis required the articulation of an evolutionary cycle, work in clinical anatomy, and an epidemiological survey. This initial period of discovery was followed by a lengthy critical period, which lasted twenty years. To avoid anachronism, one must recognize that medical thinking was bound to alternate between two positions. On the one hand, it had to integrate what it took to be implicit in the facts: Parasitic thyroiditis was the name given to a parasitic theory of goiter as it appeared in Brazil. On the other hand, it had to separate what it took to be distinct in those same facts: parasitosis on the one hand and goiter on the other. It was the epistemological prestige of endocrinology that imposed these incompatible requirements: Chagas and his opponents gave the same pathogenic explanation of the principal syndrome, myxedema. Make no mistake: Chagas did not discover American trypanosomiasis, and his opponents were not fools. Chagas and his school did not associate goiter and American trypanosomiasis but did identify the new malady with parasitic thyroiditis. His opponents did attempt to distinguish goiter not from American trypanosomiasis but from a parasitosis they could not describe clinically. The year 1935 witnessed a reorganization of medical knowledge. For the first time in the history of this disease, Romaña gave the clinical description of American trypanosomiasis. As a result, a continental scourge came into clear focus. “Chagas disease”: The title of this book, the reader will by now have gathered, masks a fundamental ambiguity. The purpose of the book will be to dispel it.

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one

Identifications

Historians of Chagas disease have written about the events that led up to the identification of this new disease entity. Often they begin with the teaching of clinical medicine at the Rio de Janeiro medical school and the founding of the Oswaldo Cruz Institute, a research center where investigators learned about new specialties such as microbiology and became curious about parasitic diseases. There, they became interested in studying the life cycles of protozoa and applying the lessons of the new medicine to public health measures. Taken together, these elements are supposed to define a causal network that contributed to, if it did not actually culminate in, Chagas’s great discovery. According to these historians, three ingredients had to come together before such a discovery was possible: an insect, the parasite that it carried, and the disease that it caused. And once they did come together, the discovery, we are told, was inevitable: “The discovery of Chagas’s disease did not occur merely by chance. Chagas’s interdisciplinary training in microbiology as well as clinical medicine and his experience with malaria probably made him especially alert to other possible vector-borne diseases. Thus, when he detected an as yet unknown trypanosome, Chagas associated this protozoon with a possible disease condition and starting investigating the environment systematically.”1 The historians also comment on Chagas’s own versions of this history, noting the methodological rules that the young Brazilian physician supposedly applied. But since Chagas’s various accounts described two symmetrical and opposing lines of research, the historians are obliged to take both into account. The first of these research programs is taken from Chagas’s early works: “In the beginning he identified the vector, then the

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parasite, and finally the disease.” The second, described by Chagas in 1922, emphasized the recognition of a pathological anomaly in Minas Gerais: “Chagas set out in search of a disease with which he was familiar, malaria, and found himself faced with a nosological context that proved difficult to interpret.”2 These historical reconstructions, reinterpreted (or not) by “social studies of knowledge,” reflect a threefold preoccupation. First, to expand the horizon of the history of science so as to show scientists at work in their culture, time, and locale. Second, to relate scientific knowledge to the sociocultural study of the conditions that render that knowledge possible. And third, to identify the characteristic procedures of Chagas’s scientific method. It is worth pausing a moment to review briefly the assumptions on which the sociocultural history of science is based. First, it assumes that its objects are self-evident, because they are associated with science and the sites where science is done. Among those sites are the laboratories in which researchers learn the latest jargon and new experimental strategies. As for science itself, sociocultural history focuses on the construction of meaning, so it naturally places the content of knowledge at the center of its inquiry. This effectively eliminates the object of history, which is the never foreordained historicity of what men do in order to be able to speak about things. Instead, sociocultural history of science deals with predetermined objects: science as social institution, the content of knowledge, scientific controversy, and the interaction of the social with the cognitive. What is even more surprising is that historians have taken what Chagas said about his work at face value, accepting his retrospective account as an accurate portrait of the way events unfolded. But the methods of an evolving research program are never foreordained. Instead of exploring the historicity of knowledge as it actually unfolded, constructivism simply brings a new methodology to the old synthesis of social history with the history of ideas, accentuating sociocultural factors, scientific results, and epistemological myth. By introducing the notion of context, sociocultural historians of science pretend to establish immediate causal linkages among phenomena that happen to occur simultaneously. The notion of “content of knowledge” is merely a synonym for scientific discourse. An epistemological myth is created by inscribing scientific method in a set of social relations without reference to the internal norms of an evolving scientific research program.

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If we hope to go beyond sociocultural history in order to discover the actual series of events leading up to the discovery of Chagas disease, we must free ourselves from this set of ideas. To begin with, we need to establish the possibility of an encounter between Brazilian medical thought and a domestic insect. Prior to any investigation, the instruction dispensed by the Cruz Institute, the research programs that it defined, and the public health tasks that it set for itself created three new possibilities: (1) to circumscribe the domain of scientific discourse; (2) to define its subject; and (3) to ascribe to it the status of an object of study. The scientific institution had three objectives: to train doctors, to promote research, and to medicalize the population. This triple function established the conditions under which it became possible to apprehend new biological objects. Parasitology, an advanced new discipline, was incorporated into the teaching of medicine. Research assimilated a new discursive practice: the formation of scientific hypotheses based on the principles of German protozoology. And the medicalization of the population included sending doctors on public health missions: The places to which they were dispatched defined the conditions for the existence of new natural objects. Unlike the “sociocultural context,” the relations among these various elements were not given in advance. They defined an a priori form of perception. Still, it is not enough simply to identify these relations: One must also show how it became possible for them to converge into a system. The discovery of a pathogenic trypanosome was a small historical event that must be seen as part of a larger scientific practice. That practice can never be defined in terms of a scientific method, despite what Chagas and his commentators say. The needs that led to the statement of a problem, the concepts mobilized to understand it, and the methods employed to resolve it were not determined by any preestablished causal network. Here, the decisive role was played by pure imagination and nothing else. That is the only sense in which the discovery was necessary. What Chagas and the historians say must therefore be stood on its head: unbeknown to the young Brazilian physician, his illogical reasoning created the concrete material conditions for the discovery of a pathogenic trypanosome. With that in mind, it becomes easier to understand the significance of the various retrospective versions of the discovery: The invention of fictitious

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narratives made it possible to hide the logic of the discovery, which could not be openly avowed.

A Medical Consciousness Oswaldo Cruz’s testament may serve as an introduction: “I wish to be spared the scene of dressing the dead; a simple shroud will suffice. There are to be no invitations to or announcements of the burial, and no mass or seventh day. No mourning either: grief exists in the heart, not in dress. . . . Let no one dress in black, especially since this is unhealthy in our climate.”3 In the nineteenth century, black had become fashionable: “In the blink of an eye, the black frock coat, black priest’s robes, the collapsible black top hat, and black carriages had turned life somber in the imperial era. The black dress of city dwellers called to mind a funeral.”4 Vaccinations had also become fashionable. The correspondence between Pedro II and Pasteur is revealing in this regard. The scientist had responded to the emperor’s public health concerns by sharing his dream of combining therapeutic trials with the pardoning of condemned prisoners. Your Majesty was kind enough to inquire about my work on rabies. My research has progressed nicely, and I continue to toil without respite. . . . Thus far I have not dared to experiment on humans, despite my confidence in the result. . . . This is where an initiative by a bold and powerful head of state could be of utmost service to humanity. If I were king or emperor or even president of a republic, this is how I would go about pardoning prisoners condemned to death. On the eve of execution, I would offer the condemned man’s lawyer the choice between imminent death and an experiment. . . . I attach so much importance to these measures that if Your Majesty were to share my views, I would, despite my advanced age and failing health, go eagerly to Rio de Janeiro to experiment with the prevention of rabies, the transmission of cholera, and cures for the latter.5

Pasteur never made the journey, but his method of attenuating microbes aroused immense hopes. In 1883, Ferreira dos Santos, a professor at the medical school of Rio de Janeiro, was sent to France to study methods of making rabies vaccine. Black clothing and vaccination expressed similar attitudes toward modernity: equality for all on the one hand, health for all on the other. In short, this was a period in which the demise of the old

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world was celebrated. In Brazil, the end of the reign of Pedro II witnessed both the abolition of slavery and the founding of the first Pasteur Institute. At about the same time another event occurred with less fanfare. In 1876, in the Report of the Rio de Janeiro Medical School, Nino de Andrade presented a scathing attack on the school’s shortcomings in the areas of medical education, research, and public health. This led to proposals for reorganizing the institution. The chair of public health, occupied by Rocha Faria, was given a laboratory. In 1887, young Oswaldo Cruz joined the faculty and discovered microbiology while studying under Faria. He soon became Faria’s assistant and was given the post of laboratory aide. In 1892, Cruz, barely twenty years old, defended a thesis in which he expressed interest in the new discipline: “No sooner had we seen, with the help of this marvelous instrument, the numerous living creatures contained in a drop of water, no sooner had we learned to work with the microscope, than we became convinced that from now on our intellectual efforts would converge, and we would specialize in a science that relied on the microscope.”6 Cruz’s early work showed that he was quite familiar with the European medical literature, and in particular with the work of the Pasteurians Miquel, Laveran, Duclaux, and Roux. In his bibliography, he cited the Annuaire de l’observatoire du Montsouris through 1891, and it is worth noting that the engraving on the title page of the volumes of the Annuaire depicted the building in which the Observatory was housed, a small Moorish structure in the Parc Montsouris. One can therefore state with full confidence that while still a medical student, Cruz was struck by the exotic edifice in the Paris park. His library still contains his collection of the Observatory’s Annuaires, starting with the 1883 issue. His earliest articles demonstrate his interest in questions of microbiology and public health. In 1893, he published “A New Apparatus for Collecting Water from Different Depths for the Analysis of Microbes.” In 1894, using the pseudonym Ignarus, he published “Causes and Methods of Protection from Cholera.” This was followed by two articles in Brasil-Médico. The first was a technical “Contribution to the Study of Tropical Microbiology.” The second, “The Hygienic Condition and Sanitary State of Gavea,” dealt with measures for cleaning up a Rio de Janeiro neighborhood. Cruz next spent a lengthy period in Paris, about which little is known. Several articles attest to his uncertainty about his professional future. He acquired competence in forensic medicine, taking courses from Ogier and

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Vibert and spending time at the laboratory for toxicology. From this work came three articles in the Annales d’hygiène publique et de médicine légale (1898): “Study of Research on Poisoning by Gas Used for Lighting,” “Research on Sperm via the Florence Reaction,” and “Toxicological Study of Ricin.” The specialization of his studies may have been related to his desire to become a professor at the medical school. It seems that Rocha had held out the possibility of a chair. Cruz subsequently deepened his knowledge of internal medicine, following courses in urology by Guyon and Albarran. These studies were probably related to his plan to specialize in urogenital practice upon his return to Brazil. Cruz also had a third area of interest, which followed directly from his youthful enthusiasm for bacteriology. In 1898, he published an account of his visit to the Institut Pasteur. Although a rather reserved, even enigmatic, person, Cruz for once allowed his emotion to shine through. The result was a rather odd text, about which it is hard to say whether it was journalistic reportage, an excerpt from his private diary, or a premonitory dream. The section of the Institut Pasteur concerned with the preparation of therapeutic serums is located on a fine estate in Garches, a small town nine kilometers northeast of Versailles. On April 6, 1898, we visited this branch of the Institut Pasteur. On this visit we were honored by the presence of Dr. Roux, Pasteur’s chosen heir, and M. Prévost, the director of the establishment. . . . The Institute of Seriotherapy stands atop a small promontory surrounded by vast carpets of green, which serve as pasture for the horses used in the production of serums. The property, which is guarded by an iron gate, stretches all the way to the forest of Saint-Cloud in the distance, with the railroad on the left and the ruins of an old castle on a promontory to the right. The latter once belonged to the Duke of Berry, and nothing remains of the ancient château but two deep moats. Closer to us, on the promontory occupied by the old castle, stands a fountain. Facing it, in the midst of a superb stand of tall cedars, a poetic arbor beneath which Pasteur spent the hottest days of summer, ecstatically contemplating the works of God that he so fervently adored. The most scientific of scientists, he saw no dishonor in turning to religion for much-needed comfort in the face of man’s ingratitude and the perfidious slander of the envious. The building is an old country house that has been adapted to its current purpose.7

After Cruz returned from Brazil, events took an unanticipated turn. In 1899, bubonic plague struck the port of Santos in São Paulo. What was to

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be done to protect Rio de Janeiro? Pedro de Affonso, who was responsible for producing smallpox vaccine, suggested to Alvim, the prefect, the creation of a municipal seriotherapy institute where antiplague serum and vaccine could be manufactured. The proposal was initially rejected but soon thereafter accepted owing to the difficulty of obtaining these rare and costly medicines from abroad. Affonso’s skill and experience as head of the Municipal Institute of Vaccination made him the obvious person to head the new agency. In October 1899, he put together a small team, which included Cruz, who was placed in charge of preparing serums and vaccines; Vasconcellos, who was Cruz’s assistant; and the medical students Dias and Fontes. Some historians maintain that Affonso hired Cruz on the advice of Roux. Affonso and Roux did indeed meet in Paris, but not until January 1900, at which time Roux advised Affonso to hire Charles Carré. Was Cruz chosen because of his relations? He was the son of Bento Gonçalves Cruz, the inspector general of public health. But this theory is no more credible than the previous one. It was probably Alvim who suggested that Affonso hire Cruz. In a letter dated October 20, 1899, Affonso offered Cruz the post of bacteriologist in chief. Alvim approved Affonso’s offer, having already entrusted Cruz with the mission of reporting on the progress of plague in the port of Santos. Cruz was already at work as of October 24, 1899. He submitted his report on November 12: “The bacterial taxonomy of the bacillus isolated in Santos patients corresponds to the species described by Kitasato and Yerson as the agent of bubonic plague. The clinical and epidemiological characteristics of the disease that has struck Santos match the classic indicators of bubonic plague. . . . The disease rampaging through Santos is bubonic plague.”8 Cruz must have been surprised by his new position. In France, he had admired the seriotherapy section of the Institut Pasteur. A year later, he was in charge of producing antiplague vaccine in Manguinhos, in an institute reminiscent of its French counterpart. The building was situated on a hill surrounded by pastureland and luxuriant vegetation. This resemblance may have been the seed of what would blossom into an ambitious project: to create in Brazil a center that would have nothing to envy in its French model. Everything about Manguinhos was reminiscent of Garches, except that there was no ruined castle. But the French castle, of which only two moats survived, was in fact a void, so perhaps we may take it as a symbol of the

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future Oswaldo Cruz Institute. Cruz invested the Manguinhos landscape with memories of his youth, images that had remained engraved in his memory. Among them was the observatory of the Parc Montsouris. From the moment he joined Pedro de Affonso’s team, Cruz had hope in the future. To be sure, the facilities in Manguinhos were still rudimentary, but he saw the modest new Institute of Seriotherapy as the ideal instrument for realizing his dreams. In 1901, the young bacteriologist presented the article “Vaccination against the Plague” as a “work of the Federal Institute of Seriotherapy of Rio de Janeiro (Manguinhos Institute).” He also mentioned his position as technical director of the former. The dedication indicates that Pedro de Affonso had become the “founder and director of the Manguinhos Institute.” Aragãno rightly saw these subtle, indeed imaginary, distinctions as marks of “the unexpected advent of the Manguinhos Institute, without any order from the government or legal document to grant it official status.”9 In other words, Cruz was already signaling the fact that he envisioned the creation of a great institute of experimental medicine, of which he aspired to be the head. From this point on, things moved quickly. The Federal Institute of Seriotherapy, attached to the General Directorate of Public Health, was inaugurated on May 25, 1900. By 1901, differences of opinion had emerged between Affonso and Cruz. In December 1901, the latter was invited by Niño de Andrade to become the head of the new Institute of Seriotherapy. In July 1901, a presidential order placed what had been the public health department of the city of Rio de Janeiro under presidential control. In March 1903, the president of Brazil made Cruz director of public health. In this key position he was able to further his plans for the institute. Special funds were allocated for the construction of the Manguinhos complex. Cruz, who knew that Brazil badly needed an institution capable of responding to all its public health needs, now had the means to carry through with his plan. When Cruz was asked about the significance of his motto, “Hope, Will, Power, Knowledge,” his answer was that everyone was free to interpret it as he wished. One could no doubt read it as the codification of his experience. Historians are wont to compare Cruz’s work with Pasteur’s, but in a sense their positions were mirror images. France had a solid scientific tradition, whereas Brazil faced an unprecedented situation. When they launched their respective projects, one man was a renowned scientist, and the other had as

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yet accomplished nothing. Brazil had no strong scientific tradition and no outstanding medical figure. But the essential point is this: The political and economic situation of Brazil favored the implantation of the Pasteurian model. Cruz’s situation was singular, and indeed fascinating, but it was overshadowed by Brazil’s emergence as a modern state. Cruz was able to capitalize on the needs created by that situation. His agenda coincided with the interests of the country’s rulers. He deserves full credit for successfully carrying out one of the missions that had earlier led Pedro II to invite Pasteur to Brazil: the eradication of yellow fever. As early as 1903, Cruz announced the broad outlines of his program, which defined the mission of the institute: “Manguinhos should be transformed into an institute for research on infectious and tropical diseases modeled on the Institut Pasteur of Paris. The institute should also be responsible for preparing all therapeutic serums and vaccines . . . as well as for teaching bacteriology and parasitology. It will be transformed into a center of experimental science, which will greatly enhance our country’s renown overseas.”10 From its inception, the Manguinhos Institute was a work in progress and a scientific testing ground. The fabrication of serums and vaccines was linked to bacteriology. The first theses dealt with questions of hematology and prevention of infectious and parasitic diseases. Examples include Etiology and Prophylaxis of the Plague (Machado, 1901), Hematology and Ankylostomiasis (Rabello, 1903), and Hematological Studies of Malaria (Chagas, 1903). Research was concerned mainly with medical entomology. Cruz, Neiva, and Chagas published a series of studies concerning various vectors of malaria. Rocha-Lima studied lesions of the liver in yellow fever, and in 1905 Chagas published his work on the prophylaxis of malaria. In public health, Cruz reorganized the protective services and relied on the first code of public health to launch measures aimed at controlling smallpox, plague, and yellow fever. The year 1907 marked a turning point. At the Fourteenth International Congress of Hygiene and Demography in Berlin, Cruz reported on the results of his prophylactic campaigns and showed a model of the building he intended to construct in Manguinhos. To explain the apparent enigma of the Moorish style of the institute, historians invoke the Alhambra. There is no need to go back that far. The architectural and functional model of the Manguinhos Institute was the Montsouris Observatory.

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The history of the Parisian model is in fact more interesting than the history of its copy in Manguinhos. It all began with a decision taken by Victor Duruy, the minister of education, and Jean-Baptiste Dumas, the perpetual secretary of the Academy of Science. The idea undoubtedly came from Dumas, who was also president of the Paris municipal council. Visitors to the Exposition Universelle of 1867 had admired the replica of the palace of the bey of Tunis that had been built on the banks of the Seine, and Parisian administrators wondered what to do with the building now that the exposition was over. They decided to turn this specimen of Moorish architecture, languishing unused on the Champ de Mars, into an observation post equipped with various laboratories. What fascinated Cruz was neither the Islamic architecture nor the laboratories but the combination of the two: the alliance of ancient oriental splendor with the latest in medical research. It is not difficult to understand why German scientists found the model of the institute that Cruz displayed in Berlin so attractive. It reflected the contemporary European taste for the exotic, exemplified by the decision to preserve the French replica of the bey’s palace. Initially erected on the banks of the Seine, Chapon’s creation embodied Muslim architecture. “The interior of this ravishing building is an exact and meticulous specimen of Tunisian civilization in its highest form.”11 In the context of the Exposition Universelle of 1867, this replica served primarily as advertising. It served French interests by symbolizing the strategic importance of the country it represented. The palace was a centerpiece in the staging of the colonial spectacle. It was also a spur to fashion. Hence it was certain to be a hit in Berlin. The model of the Manguinhos Institute reconciled seemingly contradictory demands. The German scientists could imagine that in Manguinhos they would both be able to savor the exotic and at the same time feel completely at home. Brazil thus projected the image of a civilized country. Not only was it capable of building in a style that represented the much-prized charms of Islamic art, but it could also provide visitors with laboratories as well equipped as any in Europe. Cruz’s success in Berlin was no doubt responsible for the change in tone of the Brazilian press. Cruz had been under attack for “health despotism.” Now he was hailed as a hero. As Brazil achieved renown for its work in public health, Cruz became, in Fraga’s phrase, “the Brazilian Pasteur.” The consequences of this success soon became apparent. In December 1907,

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President Affonso Penna, who had succeeded Alves, issued a decree marking the foundation of the “Institute of Medicine and Experimental Pathology.” The following year, the congress approved the official charter of what now became the “Oswaldo Cruz Institute,” henceforth an autonomous entity no longer subordinate to the Directorate of Public Health but rather attached to the Ministry of the Interior and Justice. The Manguinhos center thus enjoyed new prestige and status, and Cruz had the funds he needed to carry on with his plans. It was not exactly a private institution, but its newfound administrative and financial autonomy would prove decisive for its future. The triple vocation of the Manguinhos Institute was thus reaffirmed. For the latest in medical knowledge, the institute turned to the leading scientific centers in Europe and the United States. Aragão, for example, studied with Goldsmidt and Oswald in Germany. But specialized knowledge could also be acquired locally, because Cruz invited Schaudinn’s leading disciples to come to Brazil. The range of research broadened. In addition to medical entomology, researchers investigated the life cycles of protozoa. Aragão discovered a new phase of Halteridium in pigeons and in collaboration with Prowazeck published work on the agent of smallpox. In the area of prophylaxis, the institute responded to requests from the government and private enterprise. It was prepared to lend medical assistance anytime and anywhere, even in the most remote regions of the country. In 1905, in Itatanga in the state of São Paulo, Chagas launched his first antimalaria campaign for the Docas de Santos Company. In 1907, with Neiva and Gomes de Faria, he completed a similar mission for the department in charge of building dams on the Xerém and Mantiqueira rivers. In 1908 a malaria epidemic struck employees of the company charged with constructing a railroad in central Brazil. Chagas and his assistant Penna undertook a new prophylactic mission in the interior of Minas Gerais. Why have I dwelt on Cruz’s enterprise? Because the emergence of the new institute, its work in Brazil, and its method of operation would ultimately lead to the discovery of a certain domestic insect and thus to the discovery of crithidial forms in the intestine of the hematophage, which included a pathogenic tryapanosome, and thus a disease. Let us focus on the essential: One can interpret the relation of the institute to Chagas’s scientific discourse on several different levels. The Cruz Institute’s updating of the medical curriculum made parasitology a central discipline. To be sure,

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the teaching of protozoology did not lead directly to the discovery of new trypanosomes, but it did arouse the young scientist’s curiosity about these new objects. Without the teaching of Prowazeck and Hartmann, who were duly recruited for the purpose, the protozoon would not have been noticed. The recruitment of these scientists stemmed from the institute’s reform of biomedical research. Chagas did not see with the eyes of the German scientists, but they did shape both the form and the content of his medical discourse. The discursive practice of the young Brazilian doctor was governed by the theoretical structure of German protozoology. Finally, with the development of new forms of medical intervention, the institute was in a position to respond to the prophylactic requirements of various social actors, including both the government and business firms such as the Docas de Santos Company and the railroad. Chagas’s prophylactic mission to Minas Gerais did not lead directly to his observation of the vectors and the parasites they carried, but it did place him on the scene where such observations were possible. The Cruz Institute thus developed not the content of the new science but a new mode of perception that made new science possible: New biological objects could be seen and described in situ. Yet these conditions in themselves were not enough. They made it possible to discover the domestic insect and the crithidial forms it carried, but they did not imply the existence of a pathogenic trypanosome. In order to account for this event, which initiated research into the pathology of the disease, we must look at the working of the imagination and at the role of error and chance.

The Logic of History Historians have been quick to link the new disease to the identification of crithidial forms in the domestic insect. Chagas, we are told, immediately grasped the significance and implications of this fact: “Starting with the evolved form of the protozoon in the intestine of the host, an insect that feeds on the blood of vertebrates, and proceeding by way of extensive, persistent, and methodical investigation, [Chagas] moved confidently and firmly toward the discovery of a new morbid entity in man. This was a remarkable moment in the history of medicine.”12

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But why would the discovery of crithidial forms in the intestine of an insect inaugurate a new chapter in tropical pathology? Historians have long repeated the same explanations. In a period when the discovery of vectors of a number of major diseases had begun to lead to a reduction of mortality rates, the hunt for parasites symbolized the promise of scientific truth. That promise could be realized only by bringing together a parasite, an insect, and a disease. One had only to open one’s eyes, we are invited to believe, in order to recognize the truth. Perleth describes this medical paradigm: “Several vector-transmitted diseases caused by pathogenic protozoa were described at the turn of the nineteenth century. Thus Chagas was alert to the characteristics of these diseases. . . . Therefore, the detection of a yet unknown trypanosome prompted him to search for a related disease.”13 Lewinsohn argues that Chagas’s intimate knowledge of malaria guided his search: “It cannot of course be denied that Chagas’s intimate knowledge of malaria must have contributed to his intuitive grasp of the situation; and his speculations . . . on the ‘barber’ bug [barbeiro] as a transmitter of disease were unquestionably inspired by his knowledge of the transmission of malaria and the developmental cycles of the plasmodium in mosquito and man.”14 But neither the medical paradigm nor the analogy with malaria makes sense unless one assumes that Chagas already suspected the presence of a new pathology. The young Brazilian doctor would then quite naturally have linked the bug to the disease that was to bear his name: “For Chagas, who was aware of the discovery of hematophagous vectors and disease transmission cycles and who was intrigued by certain inexplicable local afflictions, this insect came as a shaft of light in the darkness.”15 These reconstructions are historically false. Chagas had no reason to think, a priori, that the Crithidia found in the insect were developmental forms of a pathogenic trypanosome. Not only do insects have their own parasites, but a protozoon is not necessarily pathogenic for its ultimate host. And even if it is pathogenic, it may affect animals rather than humans. The first stage of Chagas’s research had nothing to do with human pathology. History has painted the Brazilian epic in the colors of experimental medicine (in 1915, Cruz gave this common misconception the dimensions of a myth). “The main stages of the investigation, which led

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step by step to this brilliant success, may serve as a model for the application of the experimental method, in which logical induction leads to truth under the control of experiment and observation.”16 In the history of medicine, this myth has a specific function: it serves as a retrospective justification. If Chagas was working in the field of experimental medicine from the beginning, then he knew where he was headed from the outset. But this is false, and we can see why this erroneous interpretation was made. Once it was proven that the crithidial forms were those of a pathogenic parasite, it became necessary to rewrite the history of the discovery in such a way that the search for pathology preceded the discovery of the Crithidia. The need to understand a new disease and its etiological agent must have existed prior to the effort to elucidate the nature of the crithidial forms found in the barber bug. By imagining that Chagas was obsessed with the presence of an unusual pathology, one bestows on the discovery of the Crithidia a significance that it did not have at the time it was made. It is a pure anachronism to imagine that Chagas intuited the pathogenic role of the parasite from the outset. By assuming that Chagas viewed the crithidial forms with the eyes of a physician obsessed with an enigmatic pathology, historians of medicine have been able to portray him as the discoverer of a new disease. But by describing Chagas’s work in this way, they also portray the history of that disease’s discovery as a linearly unfolding process, which it was not. The actual chronology was different. The path that Chagas initially followed was not that of experimental medicine. In fact, the crithidial forms found in the intestine of the barber bug were at first linked to a harmless trypanosome found in a local monkey, Trypanosoma minasense. Why should parasitology always be guided by human pathology? It was the desire to verify the hypothesis that the flagellates found in the barber bug were developmental forms of Trypanosoma minasense that led to the unexpected discovery of a new pathogenic parasite, Trypanosoma cruzi. From that moment on, the investigation veered off in a new direction. It turned toward pathology and led to the discovery of a new disease, but by way of the experimental infection of a monkey intended to verify the (incorrect) initial hypothesis. The investigation had two distinct starting points. The first led to the discovery of the crithidial forms and then, by chance, to a pathogenic parasite, which marked a new starting point. From there the work took a turn toward experimental medicine.

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The route followed was thus the reverse of the usual one, because Chagas worked from the parasite toward the disease, though the parasite in question was not the flagellate found in the bug but the Trypanosoma cruzi identified in the blood of a laboratory animal. According to Lewinsohn, “The history of the discovery itself, unique in the annals of medicine, has been told too often and is too well known for any aspiration to originality to be entertained by one now attempting the task.”17 If history’s task were to comment on Chagas’s various versions of his own story, Lewinsohn would be abundantly correct. But in fact, Chagas’s accounts for the most part deliberately concealed the first line of research. That is why the history of the discovery remains to be written, and the challenge is worth taking up. What Chagas left in the shadows was the emergence of a new scientific practice, no part of which was determined in advance. What follows, then, is the history of an investigation that encountered its object (a pathogenic trypanosome) and formulated its project (to search for the disease caused by this pathogen) at the conclusion of an initial investigation, which capitalized on error and chance. In 1913, Brumpt listed the nonpathogenic trypanosomes found in monkeys. Among them was one discovered by a Brazilian doctor: “Trypanosoma minasense C. Chagas, 1909.—Very common in the blood of the marmoset (Hapale penicillatus), easily cultivated on chocolate agar.”18 In 1972, Hoare placed this parasite in the subgenus Megatrypanum: “Trypanosoma (Megatrypanum) minasense Chagas, 1909.” He added that “the name Trypanosoma minasense was given by Chagas (1909) to a parasite found in the marmoset, Callithrix penicillata (syn. Hapale penicillata), in Brazil.”19 Brumpt and Hoare both refer to Chagas’s paper “Neue Trypanosomen,” published in the prestigious German journal Archiv für Schiffs- und Tropenhygiene (30 [1909]: 120–122). But both make the same error: They should have written “Trypanosoma minasense C. Chagas, 1908,” in view of Chagas’s earlier paper “Trypanosoma minasense” published in Brasil-Médico (December 22, 1908, 470a). In his preliminary note, Chagas wrote: This is a large trypanosome with a more or less oval nucleus lying transversally at the center of the parasite and a small blepharoplast near the nucleus occupying roughly the posterior third of the parasite. Around the blepharoplast, in the stained preparations, a fibrillar irradiation is visible. . . . Alongside the nucleus, one observes a vacuole, whose size varies. The two

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extremities of the parasite are slender. . . . It does not appear to be pathogenic for its habitual host.

For the time, this was a good description, because Chagas noted the nucleus and the blepharoplast, the other chromatic mass in which the flagellum was inserted. This trypanosome was described the following year by Carini in another species, Callithrix jacchus, from the state of São Paulo. In 1923, Cerqueira found it in Callithrix penicillata. Later, in 1937, Rodhain encountered it in the macaque Saimiri sciureus from Brazil. In 1941, he came to believe that it was a distinct species, which he named Trypanosoma saimiri. In 1961, Deane and Damsceno found Trypanosoma minasense in various Callithrix jacchus monkeys from Bahia and confirmed that it shared common characteristics with the trypanosome previously identified by Rodhain. More recent studies by Deane and his collaborators have shown that the number of parasites in the peripheral circulation increases between noon and sunset, after which it decreases, disappearing by the next morning. Based on this periodicity, Deane concludes: “We may speculate that the natural vector of T. minasense is likely to be a hematophagous insect with a preference for feeding in the afternoon.”20 It would be a mistake to underestimate Chagas’s initial discovery on the grounds that it involved a nonpathogenic parasite of a wild monkey. In this period, parasitologists focused their attention on any and all trypanosomes. They were interested, for instance, in nonpathogenic trypanosomes found in rodents, insectivores, edentate mammals, and monkeys. Trypanosoma avicularis Wenyon, 1909, was found in the Egyptian Sandou in the blood of the zebra mouse. Trypanosoma grosi Laveran and Pettit, 1909, was found in field mice in Russia and France. Trypanosoma talpae Nabarro, 1909, appeared in Talpa europaea in England and Portugal. Trypanosoma ligeri Mesnil and Brimont, 1910, was found in an anteater (Tamandua tridactyla) in French Guiana. Trypanosoma prowazeci von Ber. Gossler, 1908, was found in a Brachyurus calvus in the Amazon basin. Trypanosoma vickersae Brumpt, 1909, was found in the blood of Macacus cynomologus and Macacus rhesus. It would be pointless to extend the list by including trypanosomes found in chiroptera, ruminants, and carnivores. These discoveries belong to the field of protozoology. Of course, they were not devoid of medical interest. To anyone interested in pathology, even the most modest discoveries were of considerable interest. To demonstrate the fruitfulness of comparative parasitology, it is enough to mention Lewis’s 1878 discovery of a benign

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trypanosome in rats. As we will see, the body of work on Trypanosoma lewisi would play an important role in understanding the developmental cycle of Trypanosoma cruzi. Furthermore, the wild animals that harbored trypanosomes could serve as reservoirs for pathogenic parasites in domestic animals and humans. Bruce, in Zululand, showed that the blood of certain wild mammals carries the trypanosome responsible for Nagana, a disease of livestock. He also showed the role of cattle and antelopes in the conservation of human virus on the shores of Lake Victoria. Nor should it be forgotten that it was natural history that called attention to the trypanosome. In 1841, Valentin discovered the first flagellate in the blood of a trout. Gruby, the following year, studied parasites in frogs and gave them the generic name trypanosome, in view of its shape, reminiscent of a gimlet. The important point is that these parasites entered the realm of pathology as etiological agents of livestock diseases. Epizooties posed an obstacle to colonial expansion: Agriculture and armies depended on domestic animals. In 1880, Evans discovered the parasite responsible for Surra, an equine disease that also afflicted cattle, camels, and elephants, which was widespread in India. In 1894, Bruce reported on the Nagana trypanosome, which affected horses, donkeys, and mules. He showed that Trypanosoma brucei was transmitted by the tsetse fly. Nagana was prevalent in Zululand, East Africa, and Uganda. In 1899, Schneider and Buffard identified the trypanosome responsible for dourine, an equine disease, also known as coital disease because it is sexually transmissible. Its agent, Trypanosoma equiperdum, had been discovered by Rouget in 1894. Dourine was endemic in Algeria as well as in a number of European countries. In 1901, Elmassian found Trypanosoma equinum in the blood of horses suffering from croup. English research in animal pathology led to further research that revealed the role of trypanosomes in sleeping sickness. Thanks to Bruce’s work on the transmission of Nagana by the fly Glossina morsitans, the discovery of this one parasitic affliction in humans pointed to the nature of the vector and the mode of infection in human trypanosomiasis. Bruce’s work marked the beginning of a new era in the study of protozoa. As early as 1902, Forde and Dutton found parasites in the blood of a patient. These were morphologically similar to Trypanosoma brucei, and Forde proposed calling them Trypanosoma gambiense. The following year, Castellani found them in the cerebrospinal fluid of a patient suffering from sleeping sickness. In 1903,

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Bruce, Nabarro, and Greig confirmed and extended the discovery of Trypanosoma gambiense in Uganda and incriminated the fly Glossina palpalis. No doubt the history of African trypanosomiasis would be unintelligible without the link to the study of livestock diseases. A history of sleeping sickness would have to follow these interwoven lines of research. But Chagas’s research was radically different from that of the English on sleeping sickness. It was a chance observation that led the Brazilian doctor to the disease that bears his name, and then only after a reorientation of his work. The conditions under which the pathogenic trypanosome was discovered were very different from those under which Trypanosoma minasense was identified. Chagas was initially curious about wild animal parasites but paid little attention to domestic insects. The Brazilian doctor had been in Minas Gerais for quite some time without noticing the presence of a certain arthropod in people’s dwellings: “We had been in the area for more than a year without becoming aware that the cottages of the region were home to a hematophagous insect commonly known as barbeiro.” Chagas was familiar with research on hematophages, however. In his work on malaria, he had described new species of mosquitoes and confirmed that they could infest homes. His name was already linked to the idea of a “household infection.” Still, there is nothing surprising about such distraction in a physician known for his competence in entomology. The focus of his mission lay elsewhere: the fight against malaria. His curiosity was soon aroused by the hematophage that people had pointed out to him. It was a local man who sounded the alarm about the barber bug: “On a trip to Parapora, where Dr. Belisario Penna and I spent the night in an encampment of engineers assigned to the task of mapping a route for the railroad, we were introduced to the barbeiro, which was pointed out to us by Dr. Cantarino Motta, the chief engineer.”21 This was a chance event, but not an inexplicable one. Chagas took an interest in the bug for the same reason that Dr. Motta was moved to show it to him. It was seen as a possible host for a still unknown parasite. The insect was therefore dissected: “Examining the content of the hindgut of specimens of Conorhinus collected in Minas Gerais from inside human habitations, we verified the presence of numerous flagellates with the morphological characteristics of Crithidia.”22 At this stage of the investigation, and in view of the fact that the Crithidia were found in a domestic insect, it would have been reasonable to assume that these were developmental forms

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of a trypanosome found in humans or domestic animals. But at the time that Chagas discovered the Crithidia, this thought never crossed his mind, because he had already formulated another hypothesis. From the beginning, Chagas saw a connection between the Crithidia and his initial discovery of a parasite in monkeys. He believed that the crithidial forms found in the bug’s intestine were associated with the benign monkey parasite. “In the monkeys (Callithrix penicillata) of the same region, we found a trypanosome, which appeared in nearly all the specimens. That is why we suspected that the barbeiro was the intermediate host: the flagellate forms in the intestine were the developmental forms of this hemoflagellate, the Trypanosoma minasense Chagas.” Chagas inserted the first key he had found into the first lock he encountered and imagined, incorrectly that he had discovered the complete life cycle of Trypanosoma minasense. But he was unaware of the high price to be paid for this solution: It required him to sacrifice the “biological sense” that would have ruled out linking crithidial forms found in a domestic insect to adult forms carried in the blood of wild animals. Still, in the end, his blunder, which led to an illogical hypothesis, turned out to be more productive than a more logical deduction would have been. Imagine for a moment that Chagas had not been guilty of these two lapses. Imagine that he had been acutely aware of biological impossibilities that in this case were also logical impossibilities. Had he noticed that Trypanosoma minasense was the parasite of a wild animal and that the Crithidia were found in a household insect, he would have suspected the existence of two cycles instead of one. This would have led him to press his research in two different directions. On the one hand, he would have looked for an intermediate host for Trypanosoma minasense in order to identify the stages of the life cycle of the nonpathogenic trypanosome of the wild monkey. On the other hand, he would have investigated the blood of humans and domestic animals in search of the trypanosome associated with the developmental forms found in the domestic bug. But this very rational plan of action would certainly have ended in a double failure. For one thing, the search for an intermediate host of Trypanosoma minasense has to this day yielded nothing. For another, Chagas would certainly have been discouraged by examining the blood of humans and domestic animals for trypanosomes stemming from the crithidial

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forms found in the insect, because the parasite fairly quickly exits the blood of the ultimate host to lodge in its tissues. In short, awareness of the conditions governing the linkage of parasites, vectors, and hosts would have led Chagas into two dead ends. By contrast, the life cycle that he incorrectly intuited temporarily resolved two problems. If the Crithidia found in the insect’s gut were developmental forms of Trypanosoma minasense, the bug was the transmitter and the monkey the definitive host. This wild hypothesis would ultimately redirect the research down an avenue so novel that Chagas, at the time he formulated it, had no idea how fruitful it would prove. When Chagas decided to test his hypothesis, his only concern had to do with the experimental protocol. He needed to infect a monkey known to be free of all contamination. This experiment could not be done In Minas Gerais, because all the monkeys in the region were infected with Trypanosoma minasense. “That is why we sent specimens of the hematophage to our director and teacher, Dr. Oswaldo Cruz, who allowed them to feed on a Callithrix.”23 The experiment planned by Chagas was thus carried out by Oswaldo Cruz in Manguinhos: “A few days later, one of the monkeys exhibited morbid symptoms, and trypanosomes were found in its blood.”24 From that point on, things moved very quickly. Cruz sent Chagas a telegram informing him of the result of the experimental infection, and Chagas returned to the institute. Roughly three weeks elapsed between the arrival of the infected insects at the institute and Chagas’s return: “Approximately twenty days after the delivery of the insects, I returned to our institute.”25 But Chagas returned to begin a new research project. In view of the unforeseen result of his planned experiment, Chagas linked the new trypanosome to the crithidial forms found in the insect. This was Trypanosoma cruzi, which Chagas named in honor of his teacher. He then investigated the morphology of the flagellate and its pathogenic properties in laboratory animals: a guinea pig, a dog, and a rabbit. In an initial paper published in Brasil-Médico, dated December 15, 1908, Chagas announced that “we are now conducting experiments on two species of trypanosome, both from Hapale penicillata.” He described the Trypanosoma minasense and ended with these words: “We will describe the other species of trypanosome, whose life cycle is of great interest, in a subsequent paper.”

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Two days later, he made good on his promise. Armed with his previous study of Trypanosoma minasense, the nonpathogenic monkey parasite, he was able to announce that Trypanosoma cruzi has “as its usual host a different mammal [from the monkey], especially since this parasite can be transmitted experimentally to dogs, guinea pigs, and rabbits.” This second paper, dated December 17, 1908, appeared not in Brasil-Médico but in the journal Archiv für Schiffs- und Tropenhygiene. The reason for this is obvious: Chagas wanted to establish his priority without divulging his discovery in Brazil, and he wanted to give himself time to do research on the pathogenic trypanosome in humans and domestic animals. Once Chagas knew that the Crithidia found in the domestic insect’s gut were developmental forms of a pathogenic trypanosome, the idea that it might be the etiological agent of a new type of trypanosomiasis was obvious. Let us pause a moment to consider the detour through the laboratory. The observation of the pathogenic trypanosome must be attributed to Cruz. It was he who arranged for infected insects to bite a monkey and who discovered the parasite in the monkey’s blood. But if we consider the various conditions that made this observation possible, the discovery surely belongs to Chagas. There were two aspects of the experiment: the procedure and the interpretation of the results. The experimental infection of a monkey by infected insects was carried out in order to verify the hypothesis that the crithidial forms were those of Trypanosoma minasense. This hypothesis stemmed from the idea that the Crithidia belonged to the genus Trypanosoma. For Chagas, therefore, the significance of the experiment was twofold: It disconfirmed his hypothesis but confirmed the idea that had inspired it. In other words, the experiment invalidated the hypothesis in regard to the species (Trypanosoma minasense) but led Chagas to the discovery of a new species (Trypanosoma cruzi) linked to the crithidial forms that he saw as belonging to the genus Trypanosoma. Chagas took all the initiative. In sending the infected insects to Manguinhos and choosing a monkey as the experimental animal, he planned an experiment that could not be carried out in Lassance. In other words, he established the concrete material conditions under which an observation could be made that led to a chance discovery. When Cruz informed Chagas of his observation, Chagas immediately knew two things without even seeing the parasite. Since it was pathogenic for the monkey, he knew that it was a new species and not Trypanosoma minasense.

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He also grasped the significance of this initial error. The point is that Cruz was the first to observe the new trypanosome because Chagas led him to it. Chagas also took an option on the future of the crithidial forms. If he had thought of it, he could have saved himself a lot of trouble by simply pointing out that everything found in the blood of an animal infected by his crithidial forms belonged to him. But Chagas could not grasp the fact that his teacher’s observation belonged to a research program that was entirely of his, Chagas’s, own devising. To understand this, he would have had to accept two things: first, that Cruz’s observation did not take any of the credit away from Chagas, and second, that chance and error can effectively advance scientific research. Had he understood this, he could have disarmed all subsequent criticism in advance by acknowledging a point that some commentators were already making: that he was not the first to see a trypanosome that he hadn’t been looking for. He could simply have said that Cruz was merely following his instructions, and that error and chance are useful only to those who know how to capitalize on them. Chagas obviously knew that it was he who had set everything in motion: His initial hypothesis had played a key role, and chance had intervened at an opportune moment. He would merely have had to explain why he entrusted the crucial experiment to Cruz. But Chagas saw this explanation as problematic: On the one hand, the hypothesis that had made the discovery possible was his, but on the other hand it had turned out to be incorrect. Chagas felt that he was caught in a vicious circle. If he insisted on the point that proved he was the initiator, he would call attention to his error while giving the impression that he had merely been lucky. We can therefore understand why he did not wish to insist on his initial hypothesis. In his own eyes it seemed to disqualify him by revealing what might be construed as a failure rather than proving that the discovery was due to him. We can also understand why he did not wish to speak of an event that he had not anticipated. In short, owning up to his mistake and to the role of accident in his discovery seemed to him the surest way to shift all the credit to Cruz. Had not Cruz made the correct observation? It was fear of seeing himself deprived of credit for the discovery that led Chagas to attempt the impossible. Instead of acknowledging his original line of research, he made up a different story, according to which he had actually found the pathogenic parasite for which he had been searching

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all along. It was a delicate situation, and all the more painful because it was a consequence of his own decision: The crucial experiment was the one that he had forbidden himself to carry out in Minas Gerais, for want of a contamination-free specimen. To save himself from this embarrassment, Chagas initially claimed the observation of the Trypanosoma cruzi. But here he faced an insurmountable obstacle, because the observation had actually been made, as we have seen, by Cruz. As a result, most of Chagas’s retrospective accounts of the discovery are riddled with contradictions. One ambiguity was already apparent in his very first paper: “After I had verified the systematic presence of numerous flagellates in the intestine of a local hematophagous insect of the genus Conorhinus, Dr. Cruz arranged for these insects to bite a specimen of Hapale penicillata, and twenty to thirty days later he found trypanosomic forms in the animal’s peripheral blood.”26 Even as Chagas was attributing the discovery to his teacher, he implicitly claimed paternity. Otherwise, why did he mention a lapse of “twenty to thirty days” (the time that passed between his sending of the insects and his return to the institute) instead of the “few days” that Cruz himself mentioned at least twice?27 Later on, this lapse of several weeks was what allowed him to claim the observation of the pathogenic trypanosome for himself. If several weeks passed between the experimental infection and the discovery of parasites in the monkey’s blood, then the discovery coincided with the series of experimental infections that Chagas himself had undertaken after returning to Manguinhos. In his preliminary note of April 15, 1909, following the detour via the laboratory, Chagas wrote: “The infection that served as point of departure for our studies was obtained experimentally by Dr. Oswaldo Cruz, who arranged for a monkey (Hapale penicillata) to be bitten by several Conorhinus sent from Minas. By way of blood inoculations and Conorhinus bites, we obtained infections in various animals.”28 Here, Chagas elides Cruz’s observation, though not his intervention. The suggestion is that Cruz merely allowed the bugs to feed on the monkeys but never examined the monkeys’ blood. But why then did Cruz recall his disciple by sending him a telegram? Finally, in the major publication of 1909, Chagas clumsily covered his tracks. He acknowledges that Cruz performed the experimental infections but says that the parasites were not discovered until twenty or thirty days later, thus allowing Chagas to claim the observation for himself: “We then

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sent the hematophages to the institute, where our director, Dr. Oswaldo Cruz, attempted to infect a macaque of the species Callithrix penicillata by arranging for it to be bitten by several specimens of the hemiptera. Twenty or thirty days after the bites, a substantial number of trypanosomes were found in the peripheral blood of the macaque, and these were entirely different from all known species of the genus Trypanosoma.”29 And that is not all. If Chagas had acknowledged that the discovery of the pathogenic trypanosome had not been foreseen, he would have been obliged to admit that the new disease had not been anticipated either. But he wanted to show that the discovery of the disease stemmed from the discovery of the pathogenic trypanosome. That is why he claimed to be in complete control of his research program. In order to conceal the fact that everything had begun with the discovery of the Trypanosoma minasense, it sufficed to invert the order of the observations and slip a falsehood into the new sequence: “No one has been able to observe a spontaneous infection in specimens of the species [Callithrix penicillata] examined subsequently, which leads me to believe that this trypanosome [Trypanosoma cruzi] is habitually hosted by another mammal [that is, not by the monkey].”30 It was no doubt perspicacious of Chagas, after the fact, to treat the discovery of Trypanosoma minasense in monkeys as the result of a thought experiment. This allowed him to assert that Trypanosoma cruzi was indeed a mammalian parasite but not a parasite of the monkey. But by writing “subsequently,” when in fact the specimens in question had been examined before the discovery of Trypanosoma cruzi, Chagas inverted the order of the discoveries. As a result, the observation of Trypanosoma cruzi appears to come first, and everything begins with the experimental infection of the monkey by infected insects. By claiming that his investigation of Trypanosoma minasense in the monkeys of Minas Gerais followed the discovery of Trypanosoma cruzi, Chagas allows readers to believe that the experimental infection was performed for the express purpose of identifying a pathogenic trypanosome. A short while later, Chagas presented a retrospective account based on this original outline. Its apparent coherence scarcely conceals its implausibility. Through a series of deductions that I will describe shortly, we were led to discover in Brazil a new human illness due to the multiplication of trypanosomes in the blood of victims. In examining a species of reduviid of the genus Conorhinus at the Manguinhos Institute, we were struck by the large

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Identifications number of flagellates in the digestive tube of the dissected insects. . . . We arranged for a macaque (Hapale penicillata) to be bitten by a number of these reduviids. We were greatly surprised, twenty days later, to find specific trypanosomes in the blood of the monkey. We immediately set out to find these parasites in a large number of monkeys. In the blood of some of them we found a large trypanosome, as yet unknown, which in an earlier note we named the Trypanosoma minasense, but we never found the trypanosome we were looking for. . . . It then became clear to us that Trypanosoma cruzi had to be hosted by a warm-blooded vertebrate other than the macaque. In search of this host, we went to northern Minas, the source of the reduviids.31

Finally, we turn to the identification of the new disease. Once the domestic insect was identified as the vector of a pathogenic parasite, two ideas inevitably followed: The ultimate host must be human, and the clinical manifestation of the disease must be close to that of sleeping sickness. Research therefore turned from the parasite toward the disease it was believed to cause. Before returning to Minas Gerais, Chagas familiarized himself with the medical literature on African trypanosomiasis. From a treatise on exotic pathology he learned about the various symptoms of the disease, such as fever, edema, enlargement of the spleen and liver, inflammation of the lymph nodes, general anemia, and nervous troubles. Back in Lassance, however, it was in a common domestic animal that Chagas found the first trypanosome: “We found a cat that had been naturally infected by the trypanosome transmitted by this hematophage. . . . Repeated examinations of the blood of children with chronic morbidity proved negative.”32 The failures pointed to a problem: The new parasitosis was probably combined with other common pathologies. One therefore needed to rule out other afflictions that might be confused with trypanosomiasis. Chagas gathered information that put him on the trail of a common childhood malady, ankylostomiasis (hookworm). Having an idea of the disease that he was looking for, Chagas was quick to realize that he had to distinguish trypanosomiasis from ankylostomiasis by showing that the stools of suspected victims did not contain worms. This allowed him to report “a well-defined human trypanosomiasis corresponding to a morbid entity commonly known as opilaçao, which clinically bears no relation to anklyostomiasis.”33 Given the difficulty of identifying specific symptoms, one may doubt that Chagas was in fact guided by such a slender thread. If he persisted in

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his research, despite his initial failures, it was because the successful experimental infections achieved at the Manguinhos Institute sustained his confidence. “In a patient with fever, severe anemia, edema, and swollen lymph nodes, we found trypanosomes morphologically identical to Trypanosoma cruzi. In the absence of other etiology for the morbid symptoms observed, and in view of earlier experiments with animals, we believe that this is a human trypanosomiasis caused by Trypanosoma cruzi and transmitted by Conorhinus sanguisuga (?).”34 The discovery was immediately confirmed by an experimental infection in a monkey. Although the search for parasites in the blood proved negative, Chagas described a second and then a third case: “Another positive result was obtained simultaneously by inoculating two guinea pigs with blood from a two-year-old child. . . . A third positive result was achieved by inoculation with blood from the guinea pig.”35

The Rights of Logic In the fall of 1910, a scientific commission composed of the leading lights of Brazilian medicine traveled to Minas Gerais. Miguel Couto recounts this memorable excursion. In Lassance, Carlos Chagas awaited us in his strange museum of curiosities. There were several dozen patients of all ages: idiots, paralytics, and cardiac patients, all goiterous, myxedematous, and aesthenic. Microscopes set up on tables exhibited live trypanosomes as well as organ preparations. In the animal section we saw infected experimental animals and test tubes filled with triatomae in all stages of development. Two years later, these sights, and the formidable impression they made on us (we could not help expressing surprise and astonishment) remain engraved in my memory and that of my companions. All this evidence was meticulously laid out for our inspection. The assembled physicians, all eminent authorities, found nothing to criticize in Dr. Chagas’s presentation of the various forms of the disease or in his analysis and interpretation of its symptoms.

The medical elite discovered the new disease in situ. Among those present were Drs. Figueira, Moreira, Pereira, Austregesilo, and Vasconcellos. The moment of celebration arrived. Standing, with Oswaldo Cruz on my right and surrounded at that point by the country’s most eminent physicians, in the marvelous majesty of the wilderness,

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Identifications and with a gravity similar to that of a religious service, I performed something in the nature of a solemn baptism, conferring with the approval of all assembled the name “Chagas disease” on this malady afflicting our compatriots, for the universal nosography.

The anecdote is for once instructive. Couto would certainly not have taken this step without Cruz’s consent. If he did not actually consult Cruz, he knew that he was not going against the wishes of the director of the Manguinhos Institute, because a recent event would have been fresh in his mind. A private meeting had taken place in Rio de Janeiro “during which Oswaldo Cruz, with an expression of satisfaction that he could not hide,” had revealed to him, Pereira, Moreira, and Austregesilo, all gathered in the home of Azevedo Sodré, “what had been a secret of the institute: Carlos Chagas, working in Minas, had singlehandedly and simultaneously discovered a disease with a variety of manifestations, its germ, and its agent of transmission.”36 Soon thereafter, Chagas was pleased to see his name linked to the disease he had just discovered. Chagas’s fears that his paternity might be challenged had therefore turned out to be unfounded. But not entirely: In November 1911, Fraga delivered a lecture on American trypanosomiasis to the Medical Society of Bahia. It was an extraordinary session. I take the liberty of proposing for the new morbid entity in man the eponymous name “Cruz and Chagas disease.” . . . The glorious name of the learned director of the Manguinhos Institute should in my opinion be associated with this great scientific event, in which he was magna pars. First, in his role as director of the institute in which the now triumphant work originated, he was the spiritual mentor and principal director of research. Second, it was Oswaldo Cruz who was the first to identify the flagellate in the intestine of the hematophage and interpret its significance as a developmental phase of the parasite of a vertebrate rather than a natural parasite of the insect. . . . He was thus a precursor in the discovery of the disease, primary discoverer of the complete life cycle of the parasite, and spiritual director and master in all difficult phases of the research, so that there can be no disputing his essential role in understanding the disease, as history will undoubtedly recognize.37

Fraga knew the institute’s founder to be a man of tact. He would never have claimed credit for the discovery. Meanwhile, Chagas, displaying exemplary modesty, had recently made the following declaration to the National Academy of Medicine, which had chosen to honor him:

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These honors belong to my teacher, who was my guide and director in all the work that I submitted to his sage judgment. . . . The homage that has just been paid me by the ex-president of the academy, the illustrious Prof. Miguel Pereira, and the applause I have received here today in my role as mere agent, actually belong to Dr. Oswaldo Cruz, who is responsible for the conclusions drawn from work to which I contributed in my small way.38

Fraga was moved by a laudable concern to give credit to both the teacher and his disciple. Not only did he mean well, but he thought that he was merely obeying the wishes of both men. He was apparently unaware that the new disease had already been baptized, because he proposed a different name from the one already bestowed by Austregesilo. But in order to take such an initiative, he must have been convinced that both scientists deserved credit for the discovery. Without the slightest hesitation, and without consulting the interested parties, Fraga indicated that the two men had worked closely together and assigned the bulk of the credit to the director of the institute. Fraga’s proposal drew no response. It represented an unacceptable compromise. At this point, neither Cruz nor Chagas was concerned with justifying the name of the new disease. As we have seen, Chagas had not awaited the initiatives of Couto, Austregesilo, and Fraga to claim paternity of his discovery. As for Cruz, it was not until 1915 that he stated his position on the matter, absolving his disciple of any suspicion. Nevertheless, Chagas’s claims prior to 1915, and Cruz’s silence, are signs of a malaise. If simply recalling the sequence of events had been enough to establish Chagas’s priority, he and Cruz would not have failed to refresh the memory of their contemporaries. Irony of history. But the actual course of events was now what Chagas had expected. Concealing this became his obsession. To have narrated the true sequence of events would have revealed his error and the fact that the discovery of the pathogenic parasite occurred by chance. It is reasonable to assume that both teacher and disciple knew that they stood on shaky ground. The true sequence of events appeared to confirm the fact that Cruz had found a parasite that Chagas had not been looking for and steered Chagas toward a disease whose existence he had not suspected. For them, paradoxically, an accurate narrative might have proved that Fraga was right. Hence there was a risk in calling attention to their collaboration and to the real reason for the detour through the laboratory: the embarrassing

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hypothesis that the Crithidia were developmental forms of Trypanosoma minasense. If the discovery was in fact the result of error and chance, then it was quite likely that credit for the spectacular turn of events would go to Cruz. His intervention had led to the success of the experimental infection. So the two men faced a delicate problem: how to ensure that the disease would be named after Chagas alone rather than after Cruz and Chagas. How could they undermine Fraga’s version of the story (and perhaps various rumors circulating at the time)? Now that Chagas was seen as Cruz’s obvious successor, the compromising version of their collaboration had to be scotched. This led to the various distorted versions of the story, which concealed the role of error and chance. Master and disciple therefore granted the rights of logic precedence over the logic of history. Let us briefly review the versions of the history given by the two doctors. Cruz’s version can be found in a lecture he delivered at the National Library of Rio de Janeiro in 1915, entitled “Some Diseases Caused by Protozoa.” Among Chagas’s various narratives, I will focus on a 1912 lecture, “O Mal de Chagas” (Arquivos da Sociedade de Medicina e Cirurgia). The choice of this lecture, given in São Paulo, is not arbitrary. First, this version of the history antedates that of Cruz. While not accurate, it is at least free of suggestion, which is not the case with some of Chagas’s post-1915 versions incorporating a methodological insight invented by Cruz. Second, the 1912 version already mentions what Chagas describes as a new line of research: from causal agent in the vector to the corresponding disease. Finally, this was the version of history that Chagas sought to publicize to the national and international scientific community. The same narrative is repeated in a series of subsequent articles published in several different languages: in Portuguese, “Trypanosomiase americana” (Revista São Paulo, 1918); in English, “American Trypanosomiasis: Study of the Parasite and of the Transmitting Insect” (Proceedings of the Institute of Medicine, 1921; Chicago Medical Review, 1923); in French, La Trypanosomiase américaine, étude du parasite et de son insecte intermédiaire (1923, in pamphlet form); in Spanish, “Trypanosomiasis Americana” (Revista española de medicine y cirugia, 1928). The versions of both Cruz and Chagas were aimed at an educated audience. Their purpose was to indicate the path to the discovery. These are edifying tales, which emphasize the talents of the young doctor and the rigor of his method. It is fair to assume that they

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follow oral versions, which by 1912 had earned Chagas international recognition. On this point, Benito Cruz’s testimony is enlightening: “This scientific achievement, the importance of which Oswaldo Cruz never tired of pointing out and which in his view had brought great prestige to the Oswaldo Cruz Institute, was widely publicized in national and foreign scientific centers, invariably associated with the name of Dr. Chagas.”39 Of course the fact that these historical accounts were provided by interested parties does not grant them any epistemological privilege. By showing that they are historically inaccurate, I do not mean to substitute denunciation for analysis. My only purpose is to bring out the inherent contradiction: There was a price to pay for attempting to twist history to fit the desires of the protagonists. We must first dispel an apparent contradiction over which many medical historians have stumbled, however. Chagas presented the events leading up to his discovery in two different ways: proceeding from the parasite in the insect to the disease, or, conversely, proceeding from an unknown pathology to its causal agent and transmitter. It would be a mistake to ask which is the “correct” version, since both were intended to conceal the path actually followed. To resolve this problem, one must notice that in all the pre-1915 accounts, Chagas placed the discovery of the parasite in the vector prior to the discovery of the disease. After 1915, Chagas added another version of the story in which he placed the discovery of a novel pathology at the beginning. Few have noticed that this second version appeared for the first time in 1915 in a text by Cruz. What led Cruz to come up with the idea that the observation of a novel pathology preceded the identification of the causal agent and vector? To answer this question, we must locate the text in which Chagas supported but did not authorize this chronological inversion of events. In 1911, in Nova entidade morbida do homem, Chagas placed the identification of the novel pathology after the discovery of the pathogenic parasite, and therefore after his return to Manguinhos. Given the habits of the barbeiro, we thought about an infectious condition within the home, and immediately the morbid condition of the inhabitants of the infested dwellings made a deep impression on us. . . . The symptomatology presented elements of trypanosomiasis in humans and domestic animals. . . . This called to mind memories of numerous patients in the region that we had explored previously, some with fevers, others apyretic. These patients always

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Identifications presented with intense morbid conditions with similar symptomatology, though we were unable to arrive at any etiological diagnosis at the time. The fever in these patients did not respond to quinine, and blood examinations did not reveal the hematozoa of malaria.40

But the fact that Chagas wrote about this memory after his return to Minas Gerais, and therefore after the detour through the laboratory, does not mean that at the time when the crithidial forms were discovered, he had established a relation between the infected insects and the very different pathology of malaria. If he had, he would have examined the blood of the suspect individuals immediately after discovering the crithidial forms in the insect. And he would certainly not have formulated the hypothesis that the Crithidia were developmental forms of Trypanosoma minasense. Yet this is the text that supported without authorizing Cruz’s decisive revision: the substitution after the fact of a past event—overdetermined by an epistemological significance that it did not have in reality—for his own memory. Cruz then assigned this discovery a triggering role. Here is Cruz’s narrative: In his fundamental work on malarial prevention, Chagas noticed that certain patients in this region, despite the rigorous antimalarial prophylaxis and treatment to which he subjected them, presented with morbid phenomena, often including febrile paroxysms, which could not be put down to malaria, because repeated examination of their blood for the malarial parasite proved negative. He was unable to link the observed symptomatology to a known morbid entity. Later, while studying the hematophagous insects in the region’s dwellings (cafuas, as they are known in Minas), he noticed a large and avidly hematophagous hemiptera known to the local population by the descriptive name barbeiro. . . . After dissecting the triatomae and examining the content of their digestive tubes under a microscope, Chagas found numerous Crithidia, which are usually developmental forms of trypanosomes.41

The rest follows from this: the discovery of the pathogenic parasite in the laboratory, followed by the discovery in Minas Gerais of an identical trypanosome in a patient. Chagas’s version is different: Let me give a rapid sketch of Brazilian trypanosomiasis. First, we found the causal agent of the disease in the posterior intestine of the insect in the form of flagellates that might belong to the genus Crithidia. Suspecting that these

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parasites might be developmental stages of trypanosomes of vertebrates, we collected several specimens of the insect from the area of Minas in which we were working and sent them to the Manguinhos Institute.

The detour through the laboratory led to the discovery of the pathogenic trypanosome. Until then, however, we had no indication of the existence of a new human disease associated with this parasite. Upon returning to the interior of Minas Gerais, to the areas in which the insect was found, and after carrying out observations and conducting research in infested human dwellings, we were deeply impressed by the general morbid condition of various individuals, in whom we verified the presence of clinical signs whose uniform character seemed to indicate a new and as yet unknown disease. This simple observation, together with our earlier studies of the parasite in the insect and the fact that this insect lives in proximity to humans, whose blood is its preferred food, led us to suspect a human trypanosomiasis, especially since among the morbid symptoms referred to above were several that justified such a finding. . . . The route to this discovery is of great interest, given that the initial impetus came from the study of a hematophage. . . . No doubt this will not remain an isolated case in the annals of medicine, and the same method of research may well lead to new knowledge in the fields of human and animal pathology.42

Very schematically, we can say that Chagas and Cruz both described a sequence in which the same key moments stand out. But they do not link these events together in the same way. Cruz suggests that it was his student’s clinical curiosity that guided his research toward the insect and the parasites it contained. At the outset, he noticed pathological phenomena so unusual that he could not relate them to any known malady, and subsequently he found the Crithidia in the body of the insect. By contrast, Chagas says that it was his curiosity as an entomologist, coupled with his interest in parasitology, that started him on his way. His work began by identification of the parasite: he initially saw the Crithidia in the gut of the insect as developmental forms of a vertebrate trypanosome. The two men describe two different orientations of the research, symmetrical and inverse. They are opposed as a habitual procedure is opposed to an exceptional one. They are opposed as the rule (given a disease, find its causal agent and vector) is opposed to an exception (given a causal agent and a vector, find the disease).

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These sequences seem so logical to them that they no doubt believed the contradiction would go unnoticed. But they didn’t for a moment believe that the two accounts were compatible. If, as Cruz said, his student had proceeded from the unusual pathology to the infected insects, logic would have required him to look for the trypanosome in the blood of suspected victims. Conversely, if everything began, as Chagas claimed, with the discovery of the Crithidia and the idea that they might be developmental forms of a vertebrate trypanosome (that is, of a trypanosome with a human or domestic animal host), logic would have required him to look for the parasite in the blood of occupants of the cottages. But the actual course of events was different from both of these accounts. The discovery of the crithidial forms led immediately to the transmission of infected insects to Manguinhos for the purpose of performing an experimental infection on a monkey. In either case, the detour through the laboratory is incomprehensible, or even pointless, because it had to lead back to whatever the logic of the respective narratives implied: for Cruz, the investigation of the places in Minas Gerais where the insects lived and the examination of individuals exhibiting an unusual pathology, or, for Chagas, the investigation of humans and animals living in the cottages. Focus on the essential: Both Cruz and Chagas are silent about the motive for the experimental infection of a monkey at the institute. Both of their versions are historically false: Not only did Chagas not behave as a curious clinician would have done, but the idea that the Crithidia were developmental forms of a parasite in man or domestic animals never crossed his mind. To put it succinctly, both versions of the history conceal the fact that Chagas ultimately discovered a disease for which he had not initially been looking. We come, finally, to the contrasting narratives of the detour through the laboratory. Here is Cruz’s version: Several specimens of infected triatomae were sent to the institute with which Chagas was affiliated and allowed to feed on the blood of a monkey. The animal fell ill after several days, and trypanosomes were seen in its blood. When informed of this finding, Chagas investigated the habits of the barbeiro and was able to confirm that it fed on the blood of humans and domestic animals. He persisted in looking for the trypanosome in these animals. Repeated examinations of human blood proved negative. The investigation of the blood of domestic animals was more successful: a trypanosome identical to the one observed in the monkey was found in the blood of a cat. Was it perhaps a

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parasite exclusively harbored by domestic animals, or did it also infect humans? Countless examinations of human blood were carried out until the trypanosome was discovered in the blood of a sick child who had come in for consultation. This trypanosome was similar to the one found in the cat and the monkey, which came from inoculation via infected barbeiros containing the Crithidia that had attracted Chagas’s attention.43

Chagas’s version coincides in part with Cruz’s: At the institute, the insects were allowed to feed on a monkey (Callithrix penicillata). A few days later, in one of the two that showed morbid symptoms, trypanosomes were found in the blood. Through a number of experiments we showed beyond any doubt that the insect was the transmitter of the trypanosome, which we named Trypanosoma cruzi, and we also demonstrated the existence of a veritable developmental cycle of the parasite in the organism of the insect, which thus played the role of an authentic intermediate host. We studied the protozoon in the laboratory and elucidated its biology. . . . This led us to look into the discovery of certain parasites of the blood. In chronic patients, who make up the vast majority of cases, we initially failed to obtain positive results, because we limited our examination to a drop of blood between slide and cover glass. An opportunity arose, however, to examine an acutely ill child with a high temperature. In the blood of this young patient, age two, we found a large number of flagellates, which we easily identified as the trypanosome transmitted by the barbeiro to the laboratory animal. This concluded the discovery of the germ of a new human disease.44

In telling the story of the experimental infection in Manguinhos, both physicians remained discreet. Cruz does not say that it was he who did the experiment, nor does he say that he saw the trypanosome in the blood of the animal. Similarly, Chagas does not say that his teacher performed the experimental infection and the observation of the pathogenic parasite. In other respects, the two accounts do not coincide. Cruz hints that Chagas did not even return to the institute and immediately set out to find the pathogenic trypanosome in Minas Gerais. He dwells at length on the difficulties his disciple encountered in the field, his perseverance, and his ultimate success in finding the parasite in a cat and, subsequently, in a young girl. By contrast, Chagas gives details of the experimental infections that he performed in Manguinhos. Not only did he prove that the insect was the transmitter of the pathogenic trypanosome, but he also studied its life cycle

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in laboratory animals. In both versions of the history, the omissions and details are far from innocent. Cruz skips over his own role at the institute and conceals his disciple’s work in the lab at Manguinhos, preferring to emphasize the events that followed the discovery of Trypanosoma cruzi. Chagas consequently seems to have been in full control of his research, completing it where it began, in Minas Gerais. Chagas, for his part, elides the role of his master and plays up his own experimental work in Manguinhos, which follows directly from the discovery of the pathogenic trypanosome— so much so that one might conclude that the discovery was his. His modest use of the plural “we” deepens the ambiguity. These narratives allow us to guess at what Chagas and Cruz were trying to hide. The teacher observed the pathogenic trypanosome in the blood of the monkey, and the disciple subsequently verified that observation. Neither version of the history is credible. Not only was Chagas not the first to see Trypanosoma cruzi, but it was a discovery that he did not expect. The experimental infection invalidated his hypothesis that the Crithidia were developmental forms of Trypanosoma minasense and confronted him with a new trypanosome. To use another lapidary formula complementary to the preceding one, one might say that these two versions of history concealed the fact that Cruz observed a pathogenic trypanosome that Chagas had not been looking for. In short, Chagas did not foresee the discovery of a new morbid entity or a pathogenic trypanosome. This is what emerges from his and Cruz’s versions of the story. Cruz and Chagas both knew all the ins and outs of the investigation. They knew that no medical investigation had been planned initially; this came only after the fortuitous observation of the pathogenic parasite at the institute. But wouldn’t the choice of the name “Chagas disease,” decided in Lassance, have been justified by the fact that the flagellate would never have been discovered had Chagas not ventured into the remote wilderness of Minas Gerais? Indeed. Everything began in Minas Gerais with a hypothesis about the crithidial forms and ended in the same region with the discovery of the flagellate in the blood of little Berenice. The fact that so much effort was expended to substitute fictitious stories for the real one is significant. At the time, the role of error and chance in science was, if not invisible, at any rate not generally acknowledged. The two scientists chose to substitute a seemingly exemplary research program for the actual story of an intellectual and experimental adventure in which a

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false hypothesis eventually led to the discovery of a pathogenic parasite and a new disease. For them, the naming of the disease after Chagas would be justified if they could show that Chagas was in full control of his research program. So they tidied up the history. But that is not all. Cruz was quick to recognize the benefits that such a discovery could yield for the institute. The Oswald Cruz Institute fulfilled three functions: the professionalization of Brazilian medicine, the development of research focusing on Brazilian pathologies, and the implementation of public health policy. To announce that American trypanosomiasis had been discovered by chance would have deprived Chagas, the institute, and the recently constituted public health authorities of an important trump card. In contrast, a transfigured history, in which the research program was made to seem as exemplary as the discovery itself, might yield three benefits. The altered narrative demonstrated the prowess of Brazilian medicine, enhanced the prestige of the institute, and pointed up the urgent need for public health interventions. It would be a mistake to see Cruz’s version as an ordinary process of scientific legitimation. It also had a publicity function. It was the centerpiece of a strategy that would produce real benefits. Cruz knew that scientific renown cannot be achieved by fiat. Achievement must be recognized. If it were enough to link a discovery to the name of its author to secure his reputation, history would be superfluous. A major discovery must be associated with an exemplary methodology. Cruz simply pointed out that “the discovery of this disease is a fine example of the power of logic in the service of science . . . a veritable paradigm for research, in which logic was all-important and chance played no role.”45 By emphasizing logic as the backbone of science, Cruz forged a solid argument in favor of Chagas’s consecration. In 1912 he received the Schaudinn Prize. Then, and only then, did Chagas’s discovery attest to the excellence of Brazilian medicine, of which his name became the symbol. If Chagas’s affiliation with the Cruz Institute had been enough to allow the latter to share in his prestige, there would again have been no need for history. Cruz was careful to make sure that his narrative contributed to a view of the institute as a center that had made historic contributions to medical protozoology. Berenice did more for the renown of the Oswaldo Cruz Institute than all its public health campaigns combined. Just as the Moorish palace was nearing completion, Chagas’s discovery proved that it was already a “functional” research facility. In 1909, his paper

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appeared in Portuguese and German in the second issue of the institute’s prestigious journal, Mémorias do Instituto Oswaldo Cruz. Penna was not mistaken when he said that “this discovery should suffice to glorify and immortalize the Oswald Cruz Institute.”46 Finally, if it were enough to juxtapose a new illness with a public health policy to make clear the urgency of action, no historical account would be needed. Cruz insisted on the fact that Chagas disease was very widespread, making it one of the most important health crises that Brazil faced. Chagas’s discovery thus attested to the excellence of Brazilian medicine, contributed to the luster of a scientific institution, and demonstrated the need for a new public health policy.

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Historians of medicine generally agree that after the trypanosome was found in the blood of little Berenice came a period in which the disease known as American trypanosomiasis was “constructed.” Chagas, they argue, quickly elucidated the stages of the parasite’s life cycle, described the various clinical forms of the disease, and came to suspect that it was widespread in the Brazilian population. But the historians also say that he committed a number of errors. He allegedly chose as his model the life cycle of the malaria hematozoon: “Unfortunately, because of their training as specialists in malaria, Chagas and Cruz expected Trypanosoma cruzi to exhibit a life cycle similar to that of Plasmodium, but no subsequent investigator has been able to confirm this.”1 He supposedly made another mistake by arguing that the parasite was transmitted by inoculation. But since this was the only known pathway at the time, Chagas had no reason to challenge it. “What could have justified doubt as to the operative mode when no one in 1909 thought of ascribing to bloodsucking insects the ability to transmit germs other than by way of the proboscis?”2 Historians also claim that Chagas confused the clinical descriptions of two different diseases in describing American trypanosomiasis: “The coincidence of thyroid hypertrophy and cretinism with infection by the newly discovered parasite led Chagas . . . to see a probable correlation between the two. The presence of edemas in all acute cases of the disease—edemas initially confused with myxedema—supported this idea.” Chagas’s misinterpretation is supposed to have had immediate repercussions on the epidemiology. The result was regrettable confusion: “Taken together, these various arguments seemed to support the idea of a 47

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correlation between endemic goiter and cretinism on the one hand and American trypanosomiasis on the other.”3 Even today, nothing escapes the watchful eye of our learned historians of medicine. Listen to Perleth: Thus, given the present knowledge of the natural history of Chagas disease, these cases were presumably suffering from disorders others than chronic Chagas disease. The pseudomyxedematous, myxedematous and the nervous stage are now in fact considered to have been manifestations of hypothyroidism. . . . It seems probable that until 1916, mainly acute cases of Chagas disease were detected, often confused with cases of hyperthyroidism and perhaps other disorders. Nevertheless, Chagas’s minute analyses of the acute stage of the disease have not lost their value with the passage of time.4

There is no need to point out the assumptions behind the historical method exemplified by the quotations above. If Chagas discovered American trypanosomiasis, his errors of interpretation and confusion must be separated from his achievement. But, conversely, if Chagas mistook an edema for a myxedema and included goiter and cretinism as signs of his disease, he cannot be said to have discovered a new parasitosis. These historians do not see that distinctions that have been familiar to us since 1935 cannot be applied to an earlier period. It was not until Romaña’s sign made it possible to identify American trypanosomiasis clinically that it became possible to distinguish discovery from error and confusion in Chagas’s medical discourse. This retrospective illusion obscures the coherence of a medical perception responsible for a single morbid entity: a thyroid disease produced by a parasite. It is therefore wrong to credit Chagas with the discovery of American trypanosomiasis while also denouncing his mistakes. A critical analysis such as Perleth’s completely misses the point: Our criteria of truth are not the same as those that governed Chagas’s medical pronouncements. What we take to be scientifically false statements were considered at the time to be true or at the very least acceptable hypotheses. Furthermore, we must bear in mind that Chagas tried to distinguish the disease that bears his name from goiter and cretinism. The fact that he linked the description of his disease to phenomena that would later become signs of different morbid entities does not imply that these distinctions already existed, nor does it suggest that Chagas was confused. If “confusion” means taking two different things to be one, then Chagas was not

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confused in the slightest, nor did he commit any error, but neither did he discover a new disease. Of all the concepts that are anachronistic in relation to what Chagas knew, the most important is the concept of American trypanosomiasis itself. The historians want desperately to relate Chagas’s descriptions to the symptoms of a parasitosis, in some cases combined with signs of hypothyroidism and in others confused with them. What they fail to see is that Chagas insinuated the description of another disease into what he called American trypanosomiasis. This was a malady somewhere between a parasitosis and an endocrine disorder, exhibiting an acute phase and a chronic phase: goiter and cretinism as they appeared in Minas Gerais. Quite simply, “parasitic thyroiditis,” as Chagas described it, was neither American trypanosomiasis nor an endocrine disorder, much less a combination of the two. How did Chagas come up with this disease, which to us appears to be a nosological monstrosity? By April 1909, the discovery of the parasite in the blood of a child seemed to point toward a “new trypanosomiasis.” But Chagas saw himself faced with three problems: the life cycle of the parasite, the clinical description of the disease, and its epidemiology. In trying to resolve these problems, he transformed his original interpretation of the new trypanosomiasis. Its cause meant that it was a form of parasitic disease, but its pathogenic process linked it to an endocrine disorder. In order to show how the concept of parasitic thyroiditis was formed, we must show how different disciplines shaped the emergence of Chagas’s medical discourse. At the turn of the twentieth century, three new disciplines transformed the medical landscape. First, protozoology shed light on the life cycle of flagellates. This involved alternation of generations: one generation reproduced by simple binary division in the form of a trypanosome and another by sexual reproduction with male and female gametes. Second, endocrinology transformed our understanding of diseases such as goiter and cretinism, which were linked to dysfunctions of the thyroid gland. Finally, microbiology made it possible to include various infectious agents in the etiology of thyroid disorders. This gave rise to a new epidemiology of goiter and cretinism. To relate Chagas’s scientific practice to these three disciplines, we must describe a crucial set of relationships. Protozoology figured in his description of the life cycle of the parasite. The German school suggested the idea of alternating generations (trypanosomes and endoglobular hematozoa).

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It supplied the rules for deciphering the life cycle of Trypanosoma cruzi. Endocrinology influenced Chagas’s clinical and anatomical examination. Associating signs of hypothyroidism with lesions of the thyroid gland, endocrinology supplied the interpretive framework that enabled Chagas to describe the symptomatology of the disease. Finally, microbiology influenced Chagas’s field work. The parasitic etiology of endemic goiter and cretinism stemmed from the toxic infectious theory of endocrine disease. With this set of relations in mind, we are in a position to grasp the significance, scope, and limits of Chagas’s work. The convergence of these three lines of research gave rise to a new medical system.

The Life Cycle of the Parasite Like natural history, protozoology requires perspicacity. Characters must be isolated, distinguished, grouped, and classified into species, genera, and families. And like biology, protozoology depends on keen observation: One must identify the various modes of protozoic reproduction. Flagellates multiply by simple binary division; sporozoa by sexual means (sporogony) and asexual means (schizogony). Research thus requires the use of the microscope and various staining techniques in order to describe the structure of the parasites, their morphological transformations, and their reproductive methods. Description is supported by graphic representation. When Chagas described young sexual forms in red globules, gamete forms in blood, the likely fertilization in the insect, and small trypanosomes in the salivary glands, he referred to drawings in plates attached to his paper. “Plate 10, figure 5: parasite totally included in red globule, without flagellum and undulating membrane . . . ; figure 20: female parasite free in plasma; figure 21: male parasite in plasma. . . . Plate 11, figures 71–72: forms in the general cavity of the insect; figures 74–75: forms in the salivary glands. . . . Plate 12, figures 78–82: uninterpreted form in the middle intestine (zygotes?).”5 The engravings showed what Chagas saw, and his observations stood as confirmation of the German theory. The Brazilian doctor observed the cycle described by Schaudinn, confirmed the sexual dimorphism reported by Prowazeck, and validated the cytological studies of Hartmann, which justified the creation of the new group Binucleata. But in describing what

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he saw and what he drew, Chagas never once imagined that his gaze and his hand were guided by the wish to find what he was looking for. The objective reference that supported his descriptions was already implicit in the result. The principles of German protozoology guided Chagas’s scientific practice and established the boundaries within which the life cycle of the protozoa could be apprehended. The order of the factors must therefore be reversed: Chagas saw with the eyes of a physician trained in the German school. His description of the life cycle of Trypanosoma cruzi revealed what the Germans taught: “We are also deeply grateful to our teachers, Professors von Prowazeck and M. Hartmann, from whom we received the finest instruction available.”6 From 1904, when Schaudinn’s famous Generations und Wierthswechsel bei Trypanosoma und Spirochaeta was published, to 1909, when Hartmann shook up the system, much research in parasitology was concerned with the life cycle of trypanosomes. In 1904, Schaudinn describe the life cycle of Trypanosoma noctua, a parasite of certain owls. He noted a growth phase, marked by alternation of generations between a free trypanosome in the plasma and an endoglobular resting phase in the form of a gamete. The trypanosomes subsequently multiply by binary division to produce young forms that can either yield new trypanosomes (so-called indifferent forms) or become males and females in red blood cells. The sexual forms continue their cycle in the stomach of Culex pipiens. After fertilization there appear male forms destined to perish, female forms that multiply by parthenogenesis, and trypanosomes, which are the only infectious forms. The following year, Prowazeck described the life cycle of Trypanosoma lewisi, which he studied in an ectoparasite, a flea of the rat. He observed sexual forms and fertilization in the body of the insect, which yielded an ookinete similar to that of hematozoa in humans and birds. The description of the life cycles of the trypanosomes of the owl and the rat revealed a previously unsuspected relationship between flagellates and sporozoites. Trypanosomes and hemosporidia were presumably two developmental forms of the same parasite. Hartmann believed that he had identified a second nucleus in the hemosporidia, and he regarded this second nucleus as a homologue of the blepharoplast. This led to combining flagellates and hemosporidia in the group Binucleata. This German work reoriented research on the life cycle of the trypanosomes responsible for

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sleeping sickness. Bruce’s experiments had seemed to indicate a direct transmission mechanism: After forty-eight hours, no infection was obtained with a fly infected with Trypanosoma brucei and Trypanosoma gambiense. But Koch thought that direct transmission did not rule out the existence of a sexual cycle. His research followed directly on the preceding work: Trypanosomes were conveyed through the bites of flies, which played the same role as mosquitoes in the transmission of malaria. In 1909, Kleine’s experiments seemed conclusive: The trypanosomes required an incubation period, because the tsetse fly did not become infectious until twenty days after its blood meal. Kleine described both plump and thin forms, which he identified respectively as male and female. The work of Schaudinn and his disciples also played a guiding role in the elucidation of the cycle of Trypanosoma cruzi. Chagas immediately noticed two stages of development of the parasite, making it both a hemosporidia and a flagellate. It belonged among the hemosporidia because Chagas detected a growth phase in red blood cells. And it belonged among the flagellates because he observed a free phase of its life in circulating blood in trypanosomian form. The morphological dualism of the parasite, evident in its endoglobular growth phase, was seen as an expression of sexual dimorphism. Chagas observed slender forms with an elongated nucleus and plump forms with a spherical nucleus and loose chromatin: The former were said to be male forms and the latter female forms. Cytological study revealed the nucleus and the blepharoplast that supposedly derived from it by heteropolar mitosis: “The treatment of this issue by the Schaudinn school [Prowazeck, Hartmann, etc.], which saw the blepharoplast as a second nucleus or locomotive nucleus in trypanosomidae, is firmly supported by these observations.”7 Unlike the Germans, however, Chagas did not observe binary division of the flagellate in the blood. He therefore needed to find out how the sexual forms whose growth he had described in the red blood cells multiplied in the vertebrate host. Chagas was thus faced with the same enigma that had puzzled Aragão a few years earlier. Aragão had searched in vain for the alternation of generations that Schaudinn had described in a pigeon parasite (Haemoproteus colombae). However, he did observe the trapping of sporozoites in the capillaries of the lung. Aragão described a multiplication of sexual forms by schizogony as follows: “The merozoite cysts appear in their initial phase at least to be separated into males and females.”8

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In Trypanosoma cruzi, Chagas suspected the existence of a process similar to the one described by Aragão, because he had found pulmonary cysts in the first autopsy. The parasite lost its flagellum and undulating membrane, then curled up, and ultimately formed a cyst in which eight ovoid merozoites appeared. This new mode of multiplication of the protozoon by regular schizogony in the lungs justified the creation of the genus Schizotrypanum. On the one hand, multiplication by schizogony and endoglobular parasitism tightened the link to the hemosporidiae. But on the other hand, the free trypanosomian stage of the parasite in the blood linked it to the flagellates. “Two biological features typical of two distinct groups of protozoa in earlier classifications—hemosporidiae and trypanosomes—are now combined in the same order, Binucleata, according to Hartmann’s system.”9 In studying the life cycle of the parasite in the insect, Chagas found both crithidial forms and small trypanosomes. Did the latter represent the ultimate phase of development of the crithidial forms? Or were the small trypanosomes and the Crithidia terminal stages of a double evolution of the parasite in the insect? From the outset, Chagas ruled out the idea that the crithidial forms were transformed into trypanosomes because he could not conceive of a developmental cycle without sexuality. Furthermore, all signs indicated that the small flagellates were the product of a fertilization. There had to be sexual union within the body of the insect, because the trypanosomes exhibited sexual dimorphism. Furthermore, an eight-day incubation period is required before the bug becomes infectious, and this delay suggests that a sexual process is at work. In the bug’s midgut, Chagas observed a schizogony giving rise to eight spherical objects: “Based on the resemblance of chromatic features, we believe that this schizogony represents the division of the spherical organisms to which we alluded, which may be ookinetes stemming from an unobserved fertilization.”10 Chagas found trypanosomian forms at every step along the usual route to the salivary glands. As for the crithidial forms, representing the parasite’s other developmental mode, Chagas believed that they were the product of reproduction by simple division. Here he was combining the views of Roubaud and Schaudinn. Like Roubaud, he insisted that the reproduction of crithidial forms was akin to what one sees in a culture: “We believe that they develop in the same way as in cultures on agar and that they play no role in the transmission of the Schizotrypanum. Roubaud mentions similar cases.” Like Schaudinn,

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he pointed to a feature of the complex life cycle of Trypanosoma noctua: “The hypothesis that these forms represent the multiplication of the indifferent forms might not be unacceptable if one agrees with Schaudinn that such forms exist. They might also represent the multiplication of unfertilized female forms.”11 Chagas therefore modified his initial idea, because he saw the Crithidia as regressive forms. In returning to the conditions of life prior to its adaptation to the blood environment, the parasite was destined to live the life of the genus Crithidia. That would explain why the flagellate, in the form of Crithidia, was found exclusively in insects liable to contaminate themselves by way of cannibalism or coprophagia. Pathological examination soon provided an opportunity for discovery. In organs Vianna found round forms of the parasite without flagella and with a nucleus and blepharoplast comparable in every respect to the Leishmanian forms. New generations of parasites formed in intracellular cysts and then entered the general circulation. “From our observations, it appears possible to assert that the trypanosome penetrates the cell, multiplies by binary division, ruptures the membrane, and escapes.”12 The discovery of this new mode of trypanosome multiplication necessitated a series of adjustments. Initially, Chagas had identified a third trypanosomian form whose morphology was different from that of the sexualized forms. It was immediately associated with the process of reproduction by binary division and given a name. Parasite reproduction in the Leishmanian form in tissue gave rise to “indifferent forms.” Schizogony was the term chosen to designate this new mode of reproduction. It was thus equivalent to the schizogony usually observed in hemosporidiae. Consequently, a new name was needed for the multiplication of gamete forms in the lungs: In the cycle of Schizotrypanum, this became known as “gametogony.” The analogy with the life cycle of the owl trypanosome described by Schaudinn seemed to rest on a firmer foundation: The two developmental paths of the trypanosomes in the vertebrate resembled the cycle of Trypanosoma noctua. On the one hand, you had binary division of the Leishmanian forms, which increased the number of indifferent forms in the blood. On the other hand, you had multiplication of the sexual elements (gametogony) in the blood cells prior to ingestion by the insect. Like Schaudinn, Chagas then noted a strict parallel between the development of the protozoon in the insect and in man. First you had a simple culture

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of parasites reproducing asexually. The Leishmanian forms gave rise to indifferent forms, while the round forms without flagella observed in the insect gave rise to crithidial forms. But neither the indifferent nor the crithidial form had the power to transmit the disease. The sexual reproduction cycle ensured the propagation of the infective forms. The gametogony in the lungs that gave rise to the sexed trypanosomes corresponded to the organisms in the insect that reproduced by sporogony and gave rise to the small infective trypanosomes. The reason for the transformations of Schizotrypanum cruzi (that is, gametogony in the lungs giving rise to sexed forms and binary division giving rise to indifferent forms) remained to be explained. Chagas argued that gametogony was due to an immune response in human blood, which produced antibodies. This explained why indifferent forms were seldom found in man. In order to avoid destruction by the trypanolytic serum, they formed cysts in the tissues. Conversely, the receptivity of the experimental animals led to proliferation of the indifferent forms at the expense of the sexed forms. In laboratory animals inoculated with blood passed from guinea pig to guinea pig, no indifferent forms were found. Chagas therefore insisted on the modes that made the parasite pathogenic. On the one hand, the infective property associated with the sexual forms ensured the propagation of the disease. On the other hand, the ability to vegetate, associated with the culture of indifferent forms, explained autoinfection in experimental animals. A number of consequences followed from this distinction. First, the linking of infective power to the sexed forms implied that the disease could be propagated only by way of human blood. Second, if only the indifferent forms could multiply in large numbers, this would explain variations in their vegetative capacity, which would be lower in humans, who produced antibodies, and higher in animals, which were receptive. This led to the idea that the parasite in a guinea pig retains the power to engender the disease but loses the power to transmit it. Finally, the various forms of experimental infection became techniques for spontaneous dissociation of the sexed and indifferent forms. But it was theory that suggested this interpretation of experiment. When a laboratory animal was inoculated with blood taken from a patient or bitten by a bug that had sucked the patient’s blood, it received the sexed forms. Gametogonic forms were indeed always observed in the lungs of these animals. By contrast, when a laboratory

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animal was inoculated with blood passed from guinea pig to guinea pig or bitten by a bug that had fed on a guinea pig, it exhibited only indifferent forms. The experimental infection of laboratory animals became a diagnostic procedure. The presence of gametogonic forms in the lungs indicated a trypanosomic infection that could rarely be detected in the examination of fresh blood. But just as Chagas came to think that he had explained the cycle of Schizotrypanum cruzi, doubt was cast on a fundamental point. In 1913, Aragão showed that the gametogony observed in the lungs was that of an accidental parasite. Let us briefly recall what led up to this: The schizogony that Chagas had observed was soon found in the lungs of animals infected by other species of trypanosome. Vianna found cysts of Trypanosoma gambiense in lung smears from guinea pigs that had been inoculated with that parasite. In lung smears from a rat infected with Trypanosoma lewisi, Carini also found schizogonic forms consisting of small cysts containing eight merozoites similar to those described by Chagas. This reproductive process seemed to be part of the life cycle of most trypanosomes. But Delanoës showed that there was no connection between the Trypanosoma lewisi and the pulmonary cysts. The inoculation of young rats with an emulsion rich in cysts was not followed by the appearance of trypanosomes in the blood. It was also found that adult rats not infected with Trypanosoma lewisi and devoid of fleas exhibited cysts. Furthermore, these cysts could be transmitted by direct contagion through females not infected with Trypanosoma lewisi to their offspring. “Carini’s cysts have nothing to do with this trypanosome. . . . Carini’s pneumocysts are therefore beyond any doubt a new parasite in rats. If this is to be a new genus, we propose to call it Pneumocystis Carinii.”13 Things now took a completely different turn. It seemed likely that the cysts observed by Chagas were not part of the life cycle of Trypanosoma cruzi. In 1912, Aragão showed that it was an incidental parasite: “In midSeptember we observed rats, guinea pigs, and dogs. These observations led us to the conclusion that the so-called schizogonies and gametogonies of Trypanosoma cruzi . . . are not part of the life cycle of that parasite. In fact, they are completely different organisms from those flagellates.”14 Chagas acknowledged his error and subsequently revised his theory: If there was no schizogony in the lung, the genus Schizotrypanum had to be dropped and the genus Trypanosoma restored.

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Logically, dispelling this illusion should have invalidated Chagas’s sexual hypothesis. If there was no gametogony in the lungs, sexual dimorphism was an illusion. Oddly enough, Chagas did not accept this corollary of his error: “Such dimorphism has been interpreted in various ways, and it is not yet possible to rule out the hypothesis of sexual differentiation.”15 In order to maintain the idea of a sexual cycle, he was forced to admit that the sexed forms came from the reproduction of the parasite in tissue in its Leishmanian form. The indifferent forms therefore vanished. By renouncing the idea of a dual mode of development of the parasite in the vertebrate, Chagas reverted to a key tenet of Schaudinn’s theory, the alternation of generations. This led to the description of a phase of reproduction by binary division in tissue alternating with a sexed phase in the form of male and female gametes in blood. This explanation had the advantage of compatibility with what he had often observed. At the beginning of the disease, trypanosomes are present in the blood, but later one finds them only in tissue in their Leishmanian form. For Chagas, the sexual forms became Leishmanian forms and vice versa. But wasn’t there a contradiction in invoking an immune reaction in the blood to explain two opposite transformations? On the one hand, the production of antibodies in the blood caused the protozoon to react to the unfavorable conditions in order to preserve the species, thus giving rise to sexed forms in humans. On the other hand, the same unfavorable conditions were invoked to explain the formation of cysts in tissue. How could the immune reaction explain both the appearance of sexual forms in the blood and of Leishmanian forms in tissue? Chagas never noticed the disparity, or even contradiction, between the sexual dimorphism hypothesis and the elimination of the condition that was supposed to allow the gametes to fulfill their function. He did not see that sexual dimorphism implied the constant presence of sexed forms in the blood. Otherwise, how could they be ingested by the insect in order to complete their union? In 1914, Chagas was still teaching the sexual life cycle in his course on Parasitology.

Parasitic Thyroiditis Clinical anatomy involves the association of symptoms with organic lesions. Symptomatological descriptions, photographs of patients, and organ

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sections show what Chagas observed: facial swelling, hypertrophy of the thyroid gland, and characteristic lesions. Chagas’s pathogenic explanations were intended as both a confirmation of an endocrine pathology in the new disease and a contribution to the study of endocrine physiology. Endocrine pathology seemed to be confirmed by the fact that hypothyroid syndromes were entirely consistent with Chagas’s histopathological examination of his patients: “All of the recognized glandular syndromes that appear systematically in numerous patients are fully confirmed by the many autopsies in which clinical features can invariably be traced to deep lesions of the endocrine glands.” But the various naturally occurring cases of the illness were tantamount to a series of planned experiments, so the new disease could also be seen as a contribution to endocrine research: “The symptoms of [thyroid] insufficiency or hyperfunction observed in various clinical cases are so uniform and consistent that this disease turns out to be an excellent experimental procedure for the study of an important and still largely unexplored chapter in the physiology of internal secretions.”16 But we need to get the causal order right: Chagas saw with eyes influenced by the medical experience of the great Brazilian clinicians. “For the clinical part of this work, we are indebted to the assistance of eminent teachers of national medicine, Profs. Miguel Couto, Miguel Pereira, Juliano Moreira, Fernandes Figueira, and Antonio Austregesilo, who shared . . . their invaluable knowledge with us. These esteemed teachers deserve credit for our best results.”17 What Chagas owed to these teachers was an interpretive framework linking pathologies to descriptions. These descriptions hinged on certain lesions of the glandular, muscular, and nervous systems. Chagas combined several different syndromes: Thyroid insufficiency was always involved, but other syndromes were also invoked at one point or another. The combination of these various syndromes yielded a classification of the various forms of parasitic infection. In Chagas’s system the symptoms of parasitosis were secondary to a number of major syndromes involving endocrine, muscular, and nervous pathologies. Research on the endocrine glands was of considerable importance in the history of medical science. The history of thyroid pathology recapitulated that of suprarenal pathology: In On the Constitutional and Local Effects of Disease of the Suprarenal Capsules (1855), Addison was the first to present a set of clinical observations linked by a glandular affliction. By ablation

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of the adrenal (suprarenal) glands, he experimentally reproduced the disease, leading him to the conclusion that the function of the adrenals is detoxification. In the pathology of the thyroid, endemic cretinism linked to goiter was already known to occur in mountainous regions. Fodéré, in his Traité du goitre et du crétinisme (1799), had described cretinism in young children. A number of morbid conditions associated with problems of the thyroid were described subsequently. In 1873, Sir William Gull described a female malady similar to cretinism, except that it developed gradually in adults. Four years later, William Ord conducted autopsies of similar cases and noted the gelatinous state of the connective tissue, which he called myxedema: The mucin was presumably not being detoxified by the thyroid secretion. Charcot discovered a myxedema that he called pachydermic cachexia, and Bourneville reported a case of congenital myxedema that he called mxyedematous idiocy. At about the same time, Kocher began to operate on goiters and observed that total ablation of the thyroid led to generalized anemia accompanied by the same myxedematous state that Ord had observed. Kocher called it Cachexia strumipriva. Following surgical removal of a goiter, the Reverdins also noted the appearance of a postoperative syndrome, which they associated with myxedema. In 1884, Schiff drew the consequences of what had been observed in the surgical clinics. He showed that removal of the thyroid in animals led to symptoms of cretinism and postoperative myxedema. On the other hand, a dog subjected to thyroidectomy survived after the graft of a new thyroid. The gland worked through chemical action, and its pathogeny was linked to thyroid insufficiency. From this point it became possible to link together the various pathological expressions of thyroid insufficiency: endemic cretinism associated with goiter, sporadic myxedema, which could either be congenital or appear later in life (acquired form in children, spontaneous form in adults). These various maladies exhibited signs of thyroid insufficiency similar to those resulting from postoperative myxedema. The investigation of thyroid pathology played a very important role in the clinical study of American trypanosomiasis. Psychiatrists focused their attention on endocrine disorders because these could explain certain neurological deficits (such as epilepsy, idiocy, and mental retardation). As it happens, it was the founders of Brazilian psychiatry who taught Chagas

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their way of seeing. His symptomatological description reveals the influence they had on him. Chagas lost little time in revising the clinical description of American trypanosomiasis. In 1909, he noted a set of characteristic symptoms: fever, adenopathy in the cervical, axillary, and inguinal lymph nodes, increase in the volume of the liver and spleen, and swollen facial tissue: “Berenice . . . constant sub-palpebral edema and temporary edemas of the head and limbs. . . . José . . . palpebral edema, deep pallor with swollen appearance. . . . Joaquina . . . generalized edema, more accentuated in the face.”18 The following year he offered a new account of the pathological symptoms. The acute form, which might or might not present with classic manifestations of acute meningoencephalitis, was characterized by two main signs: swelling of the face and hypertrophy of the thyroid gland. These pathognomonic signs were the expression of a thyroid insufficiency. The swelling of the face was no longer seen as an edema but rather as a myxedema: “This sign, which also appears in chronic forms of the disease, presents here with greater intensity, expressing a process of infiltration or very acute mucoid degeneration of the subcutaneous cellular tissue. The intensity of this phenomenon, present in children from the first days of the infection, makes it a morbid process, to borrow the excellent phrase of Prof. Miguel Couto, exclusive of schizotrypanosis.”19 The perception of myxedema, associated with glandular hypertrophy, led to an epistemological revision of the disease: “The name parasitic thyroiditis, based on the most common morbid elements of the disease, was suggested by Prof. Miguel Pereira and accepted as a felicitous way of characterizing a salient feature of the external appearance of the patients, namely, the hypertrophy of the thyroid gland.”20 Once Chagas ceased to look for symptomatic similarities between his disease and African trypanosomiasis and turned instead to an analysis of the symptoms associated with the underlying lesions, American trypanosomiasis underwent a metamorphosis. Where he had initially seen a parasitosis similar to sleeping sickness, he now saw an endocrine disease. Because of the nature of the etiological agent, it was still a parasitosis. But the physiopathological processes of parasitic thyroiditis coincided with those of an endocrine disorder. Pathological anatomy invariably revealed an inflammation of the thyroid. The coincidence or at any rate the regular succession of myxedema

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and goiter in Minas Gerais showed that one was dealing with the same malady. The pathologic identity of parasitic thyroiditis stemmed from the same morbid process. Chagas did not describe a combination of different diseases but rather defined different clinical forms of parasitic thyroiditis. In other words, he submitted symptomatological study to control by autopsy. Several signs pointed to the myxedematous nature of the swelling, which was not to be confused with an edema: here, simple infiltration of serosity into subcutaneous tissue to the point where finger pressure left a mark and resistant solid mucoid infiltration leaving no mark and presenting the sensation of crackling similar to that experienced in typical myxedema. In his first autopsies, Chagas found appreciable hypertrophy of the thyroid gland. But it was Vianna who carried out histopathological examinations and reported the existence of thyroid lesions that produced cysts with, in some cases, areas of calcification. “In the sections there are points of inflammation in the connective tissue of the organ and in some cases a very pronounced sclerosis. . . . Many of these foci show cysts of varying volume.”21 The examination of muscles and of the cerebrospinal system also revealed Leishmanian foci and inflammatory lesions. The clinical manifestations could be clearly linked to the lesions, but analysis of the morbid reactions was based on a conjectural physiopathology. The parasite might act mechanically, causing tissue inflammation until they were completely eliminated. This inflammatory reaction would have to be linked to the destruction of cells attacked by the parasite and hyperplasia of the interstitial connective tissue. The parasite might also secrete toxins with a deleterious effect on the functioning of the organ. Toxicity would have to be related to tissue degeneration. It was therefore essential to establish a series of chronic forms of the disease. At first glance, the summary of several hundred cases observed in Minas Gerais appears to have been based on comparison of clinical observations with autopsy reports. In fact, however, Chagas put together two sets of observations that did not relate to the same object of study. The first set was based on descriptions of the various syndromes seen in large numbers of chronic patients: a series of morbid signs linked to endocrine, muscular, and nervous disorders. The second set stemmed from a small number of autopsies (a dozen or so) performed on acute cases and on infected guinea pigs. In other words, Chagas linked symptoms observed in chronic cases to lesions supposedly identical to those that Vianna had previously described in a few acute cases. Each association of symptoms constituted a syndrome

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of the disease. His purpose was to identify both the seat of the disease and a principle by which its various clinical expressions could be distinguished in view of suspected lesional foci. Chagas pushed this type of analysis to the limit, systematically identifying syndromes associated with presumed lesions. First came the system of secretory glands: goiter, myxedema, convulsions, and cognitive disorders were all syndromes of hyperthyroidism. “Goiter in these areas, along with its attendant morbid symptoms, will constitute a clinical syndrome of the morbid entity produce by Schizotrypanum cruzi.”22 Chagas distinguished the mxyedematous syndrome from three others: Basedow’s syndrome (exophthalmia, tachycardia, general trembling, arterial hypertension); Addison’s syndrome (general asthenia, melanodermia); and ovarian syndrome, marked by suppression of menstrual flow or hemorrhagia, explained by cysts limited by a sclerotic tissue or even an inflammatory reaction. Then came the muscular system: The cardiac syndrome was reminiscent of Stokes-Adams disease, with a slow pulse and periods of more pronounced slowing, as well as lesions of the bundle of His. Finally, the nervous system: cerebral diplegia syndrome, accompanied by clinical signs of bulbar paralysis, related to localization of the parasite in the cortex; cerebellar syndrome (titubation, asynergy, cephalgia, vertigo) due to encephalic lesions; and Little’s syndrome, characterized by paraplegia (spasmodic rigidity rather than paralysis). This, essentially, was the set of syndromes that appeared to be based on anatomical-clinical correlations. Chagas was nevertheless well aware that there was a major drawback to this sort of analysis. It disintegrated the new morbid entity into a plethora of syndromes. Or, to put it another way, it defined the new disease in terms of a long and unremarkable list of well-known endocrine, cardiac, and nervous pathologies. How could one describe the polymorphism of American trypanosomiasis without invoking a mere collection of syndromes? Within the group of acute infections, the presence or absence of a nervous syndrome distinguished the form complicated by meningoencephalitis from that characterized solely by thyroid insufficiency. But such a criterion could not be applied to the various clinical forms of the chronic state of the disease, because the doctor faced with a superimposition of all the syndromes found himself in a quandary. Brazilian trypanosomiasis, as human pathology, appeared to be the multifarious pathology par excellence.

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Could the various chronic forms be classified in any coherent way? Chagas’s principle of classification turned on which organ systems were affected. Instead of describing all the syndromes together, he concluded, one ought to focus on various complexes of syndromes corresponding to different organ systems. But this methodological principle was still not sufficient, since all organ systems in the body were affected. Chagas therefore applied a hierarchical principle: By focusing on the organ system that was most severely affected, he could establish a coherent classification of the chronic forms of the disease. He further refined his analysis by applying two complementary principles. A principle of derivation allowed him to link certain chronic forms to acute forms. This led to observation of variations in the intensity of initial syndromes. Conversely, he applied a principle of independence to the chronic nervous syndromes. These could not be sequellae of meningoencephalic processes in the acute infection, because the acute infection was almost always fatal in such cases. Hence there must be independent chronic nervous forms due to local inflammatory processes without antecedents. But Chagas was under no illusions as to the value of this system of classification. There was no rigorous way of delineating syndromes and there were no clear lines of distinction between different clinical forms of the disease: Syndromes could easily be confused with one another. In order to differentiate them, Chagas relied on the predominance of certain elements over others or on the emergence of new elements in an otherwise steady set of symptoms. Chagas observed an incipient form of the disease, which he called “pseudomyxedema.” This was common in children up to the age of fifteen. It was characterized by mild myxedema accompanied by early signs of glandular hypertrophy, generally affecting both lobes of the thyroid. This was seen as the first stage of Charcot’s pachydermic cachexia. Hyperthyroidism was the predominant syndrome: This was the incipient goiter that Chagas had followed in a number of patients, which led to voluminous goiters in adults. The “mxyedematous” form that succeeded this was marked by accentuation of the morbid processes. The clinical expression of the myxedema was more intense and complete (moon face, parchment-like skin, skeletal lesions, and intellectual debility). These mxyedematous forms of the disease were much closer to true pachydermic cachexia. They might be compared to scrofulous cachexia resulting from total thyroidectomy.

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The group of “chronic forms with acute exacerbations” included patients with severe hypertrophy of the thyroid and signs of a new infection. The term “meta-schizotrypanosomic” was applied to cases of infantilism and old goiter resulting from the initial infection. Here, syndromes of hypothyroidism were fully in evidence. But the parasites also affected the muscular and nervous systems. This led in particular to the common cardiac form of the disease. Arrhythmia was the dominant symptom. Muscular excitability was the most affected function, leading to extrasystole. There were also irregular rhythms induced by changes in the conductivity of the myocardium. Slow and intermittent pulse was also observed. Histopathological examination of the myocardium frequently showed signs of the parasite. The nervous form of the disease presented with a wide variety of symptoms. Motor troubles were the most common: paralysis, spasmodic contractures, and marked choreiform movements of the lower limbs. Speech disturbances ranged all the way to complete aphasia, and in some cases the brain was affected seriously enough to cause mental disorders, retardation, and incurable cretinism. These various symptoms were all traced to specific lesions. The first autopsy of a child who died with signs of acute meningoencephalitis showed lesions of the cerebrospinal system, which led to the definition of the nervous form of the disease.

Epidemiological Investigation The epidemiological study of Chagas disease involved investigating the conditions that favored the incidence of the disease and determined its geographic distribution. Important factors in such a study included the age of patients and the conditions in which they lived. Knowledge of entomology was also required. The ethology and distribution of the barber bug had to be investigated and signs of infestation identified. Chagas of course noted that the distribution of infected bugs coincided with the distribution of endemic cretinous goiter in Minas Gerais. This coincidence was seen as convincing evidence of the etiology of Chagas disease, because Chagas had already proposed the theory according to which the parasite affected the thyroid gland, causing hypertrophy and myxedema. By attributing to his disease a pathogenic mechanism associated with an endocrine disorder, he was able to link it to goiter and cretinism.

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He was thus able to see an affliction that had the dimensions of a plague: Chagas disease was “one of the most vicious tropical diseases, directly responsible for a high level of mortality, especially among children, and for chronic morbid conditions rendering many individuals unfit for vital activity in the contaminated zones. In short, it is an important cause of human degeneracy.”23 From an epidemiological point of view, Chagas faced an already identified pathological phenomenon for which he proposed a new etiology. The repeated insistence that Chagas discovered American trypanosomiasis has led many people to forget that what he actually investigated was parasitic thyroiditis, that is, the goiter and cretinism prevalent in Minas Gerais. Looked at from another angle, Chagas’s epidemiological intuition was shaped by contemporary medical thinking, which granted epistemological priority to microbiology. When McCarrison proposed the hypothesis that goiter was caused by a toxin produced by an intestinal germ, he was looking at the symptom in the same way as Chagas. Indeed, Chagas readily accepted the English scientist’s hypothesis, arguing simply that in Brazil one did better to substitute a toxin produced by the parasite: “Endemic European goiter is presumably of hydric or infectious origin, while ours, which we have studied in our home state, is certainly a syndrome of parasitic thyroiditis.”24 We must therefore stand the usual argument on its head: For Chagas, theory preceded observation. Why did he propose a parasitic theory? Not because he saw a correlation between infected insects and endemic goiter and cretinism in Minas Gerais, but because he was able, at that point in time, to tie the epidemiology of goiter to the epidemiology of an infectious disease. That is why the parasitic theory trumped all others, at least in Brazil. In other words, Chagas took an old theory of goiter and cretinism and invested it with new content. This was no accident: The history of research on the etiology of endocrine disorders was closely related to the history of research on malaria, so closely that the former faithfully reproduced the latter. Physicians were quick to establish a link between goiterogenic miasmas and malarial miasmas. Both endemics existed in swampy regions and seemed to disappear with altitude. Both affected groups of individuals sharing a similar way of life. Most of the things that could be done to reduce the prevalence of malaria also worked for goiter and cretinism.

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Furthermore, both maladies had specific antidotes: quinine for malaria and iodine for goiter and cretinism. In 1870, Morel saw both malaria and endemic goiter and cretinism as the result of contamination of the atmosphere by a telluric emanation. Similarly, Koeberlé thought that the miasmatic principle of cretinism infected the air to cause a sort of “malaria” (from mal aria, bad air) that produced an intoxication of the blood. Ten years later, Laveran discovered the agent of malaria: The principle of etiological commonality indicated where to look for the agent of goiter and cretinism. In 1897, Grasset found a parasite in the blood of patients similar to the hematozoon of malaria. Jeandelize, after examining different etiological doctrines, concluded in favor of Grasset: “The hypothesis that attributes a parasitic origin to the endemic that concerns us here is the most plausible.”25 In 1898, Ross elucidated the life cycle of the parasite and showed that it could be transmitted by mosquito bite. It is easy to see why Chagas was well placed to propose the ultimate version of the etiological relationship between endemic goiter, cretinism, and malaria. The trypanosome exhibited a sexual life cycle, and the distribution of the vector corresponded to that of endemic goiter and cretinism in Minas Gerais. At a time when microbial theory was shaping revisionist theories of the etiology of endocrine disorders, Chagas was able to propose a parasitic theory of goiter and cretinism. Historians of medicine see this as an error, but they fail to see why such a theory might have seemed perfectly plausible at the time. In 1916, Bouillez, following Chagas, proposed a parasitic origin of goiter in central Africa. In 1921, Chatton and Courrier wrote: “Given the specific action of Schizotrypanum cruzi on the thyroid gland, on the one hand, and the probable wide distribution of trypanosomes of the Schizotrypanum type, on the other hand, one cannot ignore a priori the idea that such parasites might be involved in the still quite obscure etiology of endemic goiter.”26 Chagas soon had to confront a series of difficulties that forced him to modify the classic schema of interhuman transmission by way of insects. First, there was an obvious paradox: acute forms of the disease were rare, while chronic forms were common. After all, goiter and cretinism were endemic in Minas Gerais, so if these were chronic forms of the disease, then a general contamination of the population seemed to be indicated. But how did this come about? Interhuman transmission by triatomids could not account for such a general infection, because the parasites formed cysts in tissue.

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Infection therefore must have occurred at birth. But here again, Chagas could not rely solely on interhuman transmission, because the bugs lived in the home. If the infection were compartmentalized, the pathogenic environment due to infectious insects would have been limited to the home. Chagas therefore considered the hypothesis of an indirect form of contamination, complementing interhuman transmission via vectors. The importance of this shift in the epidemiology should not be underestimated. He then invoked the simultaneous action of a set of pathogenic microfoci, emphasizing the proliferation of the bugs in dwellings and the frequency of bites. In infested homes, no one could escape the contaminating bites. This explained the endemic nature of the disease in the rural population. The paradox was thus dispelled. Because the infection was general, it was rarely observed. Since all children were infected when very young, the infection passed unnoticed: “We interpret this disproportion by observing that, in view of the high epidemic index of thyroiditis, virtually all children are likely to be infected in the early stages of life, which is why the acute phases of the disease escape observation.” Chagas could then shift the infectious phase back a notch and close the loop with the chronic form. It was enough to envisage transmission in utero: “Since congenital transmission of the disease appears to be certain, one should not be surprised by the small number of acute cases of infection, because the children of the region, nearly all of whom are children of infected parents, carry the infection from the uterus, after which it can present only in its chronic stage.”27 But if parasitic thyroiditis was a congenital disease, might it be described as a hereditary-infectious pathology? How would this affect the classification based on the initial investigation of its clinical anatomy? It became necessary to distinguish the chronic forms of parasitic thyroiditis from the sorts of goiter and cretinism observed in Europe. Chagas invoked the specific character of the lesions, the symptoms, and the etiological agent. In Europe, cretinism implied a congenital lesion of the thyroid gland that affected intelligence and motility. In Minas Gerais, cases of myxedema and infantilism assumed a different aspect. Diminished intelligence was rare, and when it was observed, it occurred in conjunction with nervous disorders. “Profound disturbances of the intelligence, unlike what we see in mxyedematous idiocy in Europe, do not stem solely from mxyedematous intoxication but rather from organic lesions of the nervous system.”

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Abnormal gait, which was associated with troubles of the intellectual faculties, also depended on organic lesions of the cerebrospinal system. In Europe, heredity and drinking water counted among the causes of endemic goiter and cretinism, with water serving as a vehicle for either noxious substances or a microbe. To be sure, the children of some parents with goiter did suffer from idiocy in Minas Gerais. But heredity was not the culprit: “The epidemiological situation of children is the same as that of their progenitors.” Nor was drinking water the cause of thyroid insufficiency in the region: “All the children who live in homes infested by Conorhinus presented with hypertrophy of the thyroid gland in the first few years of life and often in the first few months, during which maternal breast feeding completely ruled out a hydric origin of the goiter.” For Chagas, it was clear that he had not confused two different diseases in his description of the malady that bears his name. His epidemiological investigation pointed to a significant coincidence: “The geographical distribution of Conorhinus is correlated with that of endemic goiter, a fact that quickly drew our attention. Thus far, according to our personal observations and information we have gathered, wherever goiter exists in Minas, the insect transmitter of the schizotrypanosomiasis also exists.”28 No goiter without insects, and no insects without unhealthy dwellings. Since it was these dwellings that encouraged the multiplication of the barber bug, parasitic thyroiditis could be classified as a disease of poverty. The epidemiological investigation faced three sets of questions. The first had to do with the insect and its relation to the reservoirs of the disease. No doubt the population of household bugs was sufficient to define the foci of infection. But where did the parasites transmitted by the bugs come from? In order for the parasite to perpetuate itself, it had to be preserved in some animal that was relatively insensitive if not completely resistant to the disease. The question of reservoirs was all the more essential because Chagas had ruled out interhuman transmission as the sole route of the disease. As noted earlier, the trypanosomes leave the blood quickly and ensconce themselves in tissue. Would it be necessary to assume constant reinfection of one insect by another? The crithidial forms propagated this way, because the reduviids are infected by coprophagy and young nymphs suck on the intestines of adults. But Chagas regarded the crithidial forms as inoffensive: Only the trypanosomes propagated the disease.

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It was therefore essential to locate a source where the triatomids could obtain parasites. Chagas’s search for the natural repository was guided by the existence of a precedent. In Argentina, after the discovery of Trypanosoma equinum, the agent of equine trypanosomiasis (croup), Elmassian and Migone investigated the blood of animals in the region. In 1910, they found the parasite in a large rodent known as carpincho (Hydrochoerus capybara). A relation was thus established between the epizooties of carpinchos and horses. The following year, Neiva identified this animal trypanosomiasis in various states of Brazil and found its repository, the capybara. This work on the natural cycle of the causal agent of croup suggested a lead. The reservoir of the agent of American trypanosomiasis might be, if not a rodent, than at any rate a forest mammal close to the rodent order. “In the area of our current work on Brazilian trypanosomiasis, in the burrows that are the natural home of the armadillo (Tatusia novemcincta), we found instances of Triatoma geniculata, adults, nymphs, and larvae. In the hindgut of this hematophage, we verified the presence of flagellates, some with the morphology of Crithidia, others with the characteristics of the genus Trypanosoma.”29 Shortly thereafter, Neiva identified a new vector of trypanosomiasis and its reservoir: Triatoma brasiliensis, which was also found in the wild in a small rodent of the caviidae family. The primitive habitat of this species is the nest of Kerodon rupestris. A second set of questions now arose. On the one hand, the reservoir was a wild animal that provided sylvan insects with a source of blood. On the other hand, the domestic insects lived in close proximity to their new hosts, humans and domestic animals. It was therefore necessary to elucidate the process of adaptation of the wild insects. The “infectiveness” of the parasite, which was responsible for the emergent disease, had to be looked at now in terms of behavioral changes in the insects. Approaching the question from both ends, Chagas was in a position to formulate a number of hypotheses concerning the natural history of the disease. Everything began when man moved into a new environment. Chagas quickly suspected that American trypanosomiasis was a recent disease, if not in Minas Gerais as a whole, then at least in the places where he observed it for the first time. Indeed, Lassance was in a unique historical situation, ideal for an emergent disease. The nucleus of the population had formed when the railroad was built. During the first two years of the town’s existence, insects were

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rarely seen. Four years later, Chagas observed the Conorhinus in nearly every home. Neiva reported the opposite phenomenon. When humans abandoned a dwelling, the insects vanished within a month and moved to neighboring homes. The idea that the bugs had only recently adapted to the new environment seemed all the more persuasive after study of their behavior showed that it was not yet firmly established. Neiva noticed that the female laid her eggs differently depending on the place in which she deposited them. In dwellings, the eggs were arranged in a string in cracks in the walls. But if the bugs were placed in cages, they once again began to lay as they did in their natural environment. “At the moment, it is a domestic insect. It is probable that this is a relatively recent adaptation, because when specimens are placed in cages containing green leaves, they lay their eggs in clumps on the leaves, as is the rule for representatives of this family.” The different ways in which the domestic cycle became established were related to the discovery of the sylvan cycle of the virus reservoir. Neiva emphasized the role of harnesses and saddles as the vehicle of choice for sylvatic triatomid. One observed this in Mato Grosso, “where the inhabitants saddle their horses with a type of saddle very propitious to the concealment of insects. We believe that this is the main way in which isolated residences are infested.”30 A third and final series of questions derived from the previous set. Man’s penetration of the natural environment was responsible for bringing together the wild and domestic cycles, but the parasite and its vector were not yet entirely dependent on man. If Chagas disease was an emergent malady, how could it also be a widespread scourge? Weren’t these two ideas contradictory? To dispel the paradox, one had to identify the various factors that could compensate for the absence of strict adaptation, not only of the parasite to the vector but also of the vector to its new definitive host. To be sure, a new pathology is not compatible with strict adaptation of the parasite to a few privileged intermediate hosts. But the low specificity of the parasite should not be seen as an obstacle to the diffusion of the disease. Chagas disease could be counted as an epidemic because the parasites could use different species of reduviids as hosts in their evolutionary cycle. Neiva reported the presence of patients with signs of parasitic thyroiditis in zones where Triatoma megista was not found. “In compensation, however,

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we found large numbers of Triatoma sordida Stal, whose frequency in other zones previously ravaged and infested by Chagas disease repeatedly impressed us.”31 Medical entomologists quickly compiled a long list of vectors naturally infected by the parasite. In 1914, Neiva had already identified several dozen species of the genus Triatoma. Protozoologists also emphasized the ubiquity of the parasite and signaled the stabilization of the virulence of Trypanosoma cruzi in various species of different genera, such as Triatoma and Rhodnius. “One fact can be stated from the outset: Trypanosoma cruzi can evolve in any species of the genus Triatoma, as experiments carried out by Brumpt and by us have shown.”32 Biological study of reduviids showed that they were bloodsuckers par excellence. Long-lived, they consumed several blood meals at different stages of development (larva, nymph, insect). Hence the overall transmission rate was likely to be high if blood meals were frequent. In this respect the vectors of American trypanosomiasis differed from those of sleeping sickness: in the case of sleeping sickness, the trypanosome had adapted to the Glossina, but in Chagas disease the parasite was found in many arthropods. Chagas’s medical system was remarkably consistent. His solutions to the problems raised by the life cycle of the parasite closely matched his clinical and epidemiological accounts of the disease. Taken together, these formed a self-reinforcing system. The life cycle of the trypanosome included an inoculative pathway. This mode of transmission accorded with the results of clinical examination. Inoculated by the bug, the parasites passed into the bloodstream and reached various organs. This led to infection of the glandular, muscular, and nervous systems, which Chagas saw as the source of symptomatological manifestations of the disease. Broadly speaking, thyroid lesions explained the myxedema and thyroid hypertrophy, which were the most salient signs of the disease. This clinical picture also accorded well with the epidemiological findings, which led to a parasitic theory of goiter and cretinism in Minas Gerais. Chagas’s concept of a parasitic agent responsible for an endocrine disorder described not so much a new parasitosis as a new etiology of goiter and cretinism as they occurred in Minas Gerais. Although Chagas disease was a form of parasitic thyroiditis, his concept of the disease was not that of a parasitosis.

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Villela contended that Chagas’s work had led to neglect of the problem of goiter in Brazil: “It can be argued that indifference to the problem of prophylaxis of endemic goiter in Brazil stemmed from the frequently asserted relationship between goiter and Chagas disease.”33 Oddly, Villela failed to see the corollary of this proposition: that the formation of the concept of parasitic thyroiditis stood as the major obstacle to the elucidation of the nature of American trypanosomiasis. Chagas’s thinking heavily influenced the course of research on the new disease. Historians of medicine have overlooked this and have therefore also missed the fact that a period of latency separated Chagas’s formulation of his medical system from the epistemological revision that had to take place before the concept American trypanosomiasis could be formulated. There is nothing paradoxical about the idea that the strong point of Chagas’s system would ultimately prove to be its weak link. When it finally gave way, nearly the whole edifice vanished with it, making room for a new picture of the disease. But let us not get ahead of ourselves. As word of Chagas’s work spread, his life cycle of the parasite and clinical and epidemiological accounts of the disease began to be called into question. Critics attacked each of these points, but the criticism alone was not enough to bring down the edifice.

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Historians of medicine are wont to say that the “construction” of American trypanosomiasis was followed by a period of “deconstruction.” This supposedly began in Argentina when Kraus attacked Chagas’s work. But it attained its acme, we are told, with the polemic that erupted in 1923 at the National Academy of Medicine in Rio de Janeiro. As for the motives behind these attacks, the historians are inclined to see a desire to discredit the work of Chagas. Cruz’s impending demise allegedly led Kraus to organize a plot with the assistance of Neiva: “Oswaldo Cruz, who had retired to Petropolis, was on the brink of death. In Argentina, Neiva was seen as one of his ‘most prominent disciples.’ . . . He happened to find himself at the exact point of origin of the first ‘attack’ on Chagas disease.” The first blow was a critique of the inoculative pathway: “Neiva formulated the hypothesis that humans are infected by the excrement [of the insect], which contains infective forms of the trypanosome, by way of lesions in the skin due to scratching or via the mediation of mucus.”1 Kraus, it is alleged, then struck a second blow by challenging the clinical descriptions of the new disease: “Kraus, who had found infected triatomids in Argentina but no clinical sign of the disease, challenged the veracity of Chagas’s published documentation.”2 Finally, a third and decisive blow was supposedly struck by the epidemiological investigations of Kraus’s collaborators Rosenbusch and Maggio. Not only did they find that goiter and cretinism were apparently not consequences of contaminated insect bites, but they also failed to find the acute form of the disease. “Kraus reached truly disappointing conclusions: The pathogenic action of Trypanosoma cruzi was an illusion, American trypanosomiasis was a mythical disease, and Chagas disease did not exist.”3 73

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Having invented these three problems, the historians then use them to evoke the great debates that supposedly divided medical opinion. They would have us believe that a major conflict pitted adversaries against proponents of Chagas disease. On the one hand, Kraus, Parreiras, Horta, Peixoto, Aragão, and Vasconcellos denied the existence of the malady, while on the other, Carini, Escomel, Villela, Segovia, and Tejera confirmed the Brazilian physician’s major discovery. Long before Romaña, they insisted, Chagas showed the way and glimpsed the extent of the disease. He was right; his adversaries were wrong; and the attacks of the opposition were totally unwarranted. These historical reconstructions miss the point. Long before the work of Kraus and Brumpt (and not Neiva, who merely verified the Frenchman’s results), questions had been raised about Chagas’s work. To begin with, there was skepticism about the life cycle of the parasite. As early as 1910– 1911, the English scientists Bagshawe, Balfour, and Minchin expressed doubt about Chagas’s description of the life cycle of Trypanosoma cruzi. They were suspicious of gametogony in the lungs, of the endoglobular phase, and of fertilization in the insect. Minchin hit the nail on the head: In Chagas’s account of the cycle, he saw “further proof of the supposed affinity of the trypanosomes and malarial parasites—a doctrine which is one of the foremost tenets of the neo-Schaudinnian school.”4 Later, Chagas’s pathological anatomy was also challenged. In 1914, Mayer and Rocha-Lima expressed doubt that the parasite forms cysts in the glands and were skeptical of the lesions described by Vianna: “The thyroid gland, lungs, and testicles are undamaged: No parasites were found in these organs.”5 Finally, the parasitic etiology of goiter caused difficulty. Carini thought that the new theory required experimental verification. Kolle, a member of the Swiss National Goiter Commission, injected a culture of trypanosomes into the artery of the thyroid gland of a rabbit: The result was negative. But it was McCarrison who, as early as 1913, suspected that the description of parasitic thyroiditis might be mixing up two different diseases: “We must not lose sight of the possibility that a trypanosome infection may coexist in the same individual with goiter initiated by the endemic influence I have indicated to you. . . . The only criticism of Dr. Chagas’s admirable work which I am at present disposed to make is that he does not appear to have excluded, in a manner which leaves no room for doubt, the possibility that

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the form of trypanosomiasis which he has described may be an infection superimposed upon ‘endemic goiter,’ and not, as he considers the infection to be, the veritable cause of this malady in Brazil.”6 The work of Brumpt, Kraus, Maggio, and Rosenbusch followed directly from these early criticisms. There was no deconstruction or conspiracy, only objections of a scientific order. But as these critiques were pursued to the limit, profound differences were bound to emerge. It is a mistake to see the second period of the history of Chagas disease solely through the filter of the polemic that appeared to end it. The methodological bias of the historians is obvious: They seek to elucidate a scientific debate by relating it to a later conflict, which seized on that debate and distorted its terms. This retrospective distortion has three consequences. First, it makes it impossible to understand the reasons for the new research. Second, it fails to grasp the significance of the critiques of Chagas’s medical system. Finally, it forces the historians to look for a conspiracy whenever any sign of discord appears. We need to describe the methodological innovations on which the critiques of Chagas were based. The key to everything is the chain of deductions that led to the identification of what Brumpt, Kraus, and Kraus’s collaborators already considered to be errors. This marked the beginning of three processes that eventually undermined Chagas’s edifice. Brumpt challenged the life cycle of the parasite, Kraus revised the clinical interpretation of parasitic thyroiditis, and the Argentinians critically examined his epidemiology. The grounds for these three reexaminations were serious and complex. Several points of Chagas’s system had already come in for criticism from Minchin, Rocha-Lima, and McCarrison. But what allowed Brumpt, Kraus, and Kraus’s collaborators to transform these early objections into a radical critique was a novel perception of the whole set of problems that Chagas had confronted. Of these, the best known is his (erroneous) description of parasitic thyroiditis, but this is also the least well understood aspect of the story. Little notice has been taken of the fact that the epistemological priority of endocrinology imposed an absolute limit on scientific debate. At this point in time, disagreement did not extend to the significance of the most salient pathological phenomena. Chagas and his adversaries agreed that myxedema and thyroid hypertrophy were signs of hypothyroidism. The point of contention at the time was the agent responsible for these disorders.

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When different causes are adduced for the same pathological phenomena, controversy is inevitable. Instead of a disease caused by a trypanosome, Chagas’s adversaries saw a hereditary-infectious etiology. To be sure, a vehement polemic did erupt in Brazil in 1923, but it was not on the same level as the scientific debates. Theoretical results isolated from their premises were invoked to resolve conflicts of another order. Vasconcellos’s attacks on Chagas should be seen as a settling of scores. The fact that credit for the discovery of Trypanosoma cruzi was at the heart of the polemic is sufficient evidence of this. It is a mistake, however, to confuse a conflict of interest with a scientific controversy.

Triple Critique Several factors contributed to the critique of Chagas’s medical system: familiarity with the Brazilian physician’s work, the mobility of scientists, an experiment in parasitology, and the probable existence of the disease in Argentina. It was no accident that Brumpt attempted to resolve the issue of the life cycle of Trypanosoma cruzi. In 1912 he was put in charge of reorganizing the parasitology laboratory of the São Paulo medical school. While traveling across Brazil, he made a detour through Lassance, but it was in the Bahia region that he observed the trypanosomes in Triatoma megistus. There was no reason not to collect infected specimens and cultivate lines of organisms obtained by passage through a series of experimental animals. The actual unraveling of the life cycle of the parasite took place in Brumpt’s laboratory at the Faculty of Medicine in Paris. Argentine doctors were among the first to take an interest in Chagas’s work, because Lozano, after visiting the Cruz Institute, had given a series of lectures on the new disease in Buenos Aires. At about the same time, Maggio visited Rio de Janeiro and brought back infected guinea pigs, photographs of patients, and organ sections showing Leishmanian foci. In Argentina, the study of regional pathologies happened to be among the major concerns of the department of public health. That was why Kraus called on the services of Neiva. Sent out to work in the northern provinces, Neiva was assigned to study the biology of the protozoa and arthropods associated with malaria. Hence it is not surprising that the first epidemiological studies of Chagas disease were carried out in Argentina.

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Lozano soon noticed the resemblance of parasitic thyroiditis to certain endemic maladies: “It is possible that Chagas disease also exists in certain regions of [Argentina] in which goiter is endemic and exhibits characteristics that are similar to if not identical with its characteristics in the state of Minas, where the parasite and its transmitting vehicle were discovered.”7 But for these concrete, material factors, criticism of Chagas’s work would not have been possible. Nothing would have come of them, however, had other scientists not noticed the theoretical presuppositions, hasty inductions, and methodological errors on which Chagas had based his system. As we have seen, Chagas relied on German protozoology, the results of a few autopsies, and epidemiological data gathered in his own investigation. In 1911, Bagshawe, Balfour, and Minchin expressed doubts about his description of the life cycle of the parasite. Brumpt was able to transform this early skepticism into a systematic critique in part because he was associated with a group of scientists determined to undermine the authority of German protozoology. The work of Edmond and Étienne Sergent, Alexieff, Salvin-Moore, Breinl, Hindle, Strickland, and Patton had pointed to shortcomings in the theories of Schaudinn, Prowazeck, and Hartmann. In his description of the life cycle of Trypanosoma noctua, Schaudinn had confused the cycles of different parasites, and, furthermore, Culex pipiens was not the intermediate host. Prowazeck had described a sexual cycle in Trypanosoma lewisi that other scientists were unable to reproduce. The order of Binucleata proposed by Hartmann turned out to be illusory. In Brumpt’s view, trypanosomes did not exhibit alternating generations or sexuality: “I have seen nothing of the kind in the life cycles of the various vertebrate trypanosomes I have studied.”8 In 1914, Mayer and Rocha-Lima conducted an autopsy of an infected monkey without finding the thyroid lesions reported by Vianna. But what allowed Kraus to question Chagas’s clinical descriptions of the disease was the faulty reasoning behind them. Not only were the lesions of the thyroid not confirmed, but a dozen histopathological examinations of acute cases did not constitute an adequate basis for explaining the chronic forms of the disease. Chagas was guilty of hasty generalization: “It is problematic to deduce the chronic forms of Chagas disease, including spasmodic paralysis (diplegia) as a special form, from observations of the parasite in acute cases.”9

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In 1913, McCarrison suspected that parasitosis occurred along with goiter in cases where Chagas saw only parasitic thyroiditis. What allowed Kraus to move beyond suspicion to irrefutable objection was his detection of a methodological flaw in Chagas’s work. The mere coincidence of infected bugs with goiter was not enough to establish a causal relation. Chagas had failed to take the necessary precautions to place his work above suspicion. “In order to establish a new type of disease, which in many respects resembles endemic goiter and cretinism, it would have been necessary from the beginning to look for infected insects and the disease in areas where endemic goiter and cretinism are rare or nonexistent.”10 The diversity of modes of reproduction posed a series of questions to protozoologists. In studying the life cycle of a trypanosome, the first question to be answered was whether its life cycle included a sexual phase similar to that of the malarial hematozoon? Or did it undergo a series of morphological transformations owing to simple binary division? If trypanosomes in rodents completed their life cycle in the hindgut of the transmitting insect, did it not stand to reason that vectorial transmission proceeds via the contaminative rather than the inoculative pathway? Once scientists began to question the work of the German school, they were forced to reconsider all the research the Germans had inspired, and in particular the life cycles of Trypanosoma lewisi in the rat flea and of Trypanosoma cruzi in the barber bug. But the critique of Schaudinn’s theory is not the main point here. It was only the negative counterpart of an important experiment in parasitology that tied together a new set of objects, concepts, and theories. A new set of ideas arose, opposed almost point by point to the ideas of German protozoology. The Germans relied on three principles: sexual differentiation, fertilization in the vector, and alternating trypanosomic and hemosporidic forms in the vertebrate host. But what if the male and female forms were purely illusory? Kraus believed this and set out to describe the morphological differences that had misled his predecessors: The young trypanosomes were slender, whereas the adults were plump. The concept of the life cycle was extended: first reproduction by sporogony, then reproduction by schizogony (sporozooa) in a process characterized by the polymorphism of the parasite and its multiplication by binary fission in the crithidial phase (flagellates).

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This new life cycle theory, with its variety of morphological forms, linkages, and ordered series, reflected another new theory, this one phylogenetic. The blood-borne parasites of vertebrates were said to derive from primitive parasites of insects that had gradually adapted to the blood environment. This dual classification suggested an entirely different natural history for this type of organism, in stark contrast to that proposed by the German theorists. Instead of evolving toward the group of hemosporidiae with its complex forms of reproduction, the trypanosome was regressing toward its ancestral structures. The forms Crithidia, Letomonas, and Leishmania corresponded to different genera of invertebrate parasites. The new theory began in European laboratories, where Trypanosoma lewisi was the focus of attention. Not only was the rat a cosmopolitan species, but its trypanosomes were transmitted by fleas that were easy to manipulate after anesthesia. Criticisms of Schaudinn’s work were soon extended to the work of Prowazeck, who had discovered the sexual cycle of Trypanosoma lewisi in rat fleas. In 1918, Swellengrebel and Strickland reported that what Prowazeck had taken to be sexual dimorphism was in fact morphological diversity of the crithidial forms. They also described a cycle that could not be reduced to a simple parasite culture. The trypanosomes ingested with the blood multiplied in the crithidial form and reverted to trypanosomal form in the hindgut of the insect. Shortly thereafter, Brumpt described the full cycle of Trypanosoma lewisi as follows: “The blood-borne trypanosomes are transformed in the digestive tube of various species of insect into Crithidia, . . . which actively divide and give rise after a varying number of days to small trypanosomic forms, which infallibly infect the rat and which I propose to call ‘metacyclic trypanosomes.’ ”11 This concept led to the proposal of a new life cycle of the trypanosome. The return to the typical form made it possible to speak of authentic evolution rather than mere culturing. But how did the fleas transmit the infection from rat to rat? Minchin and Thomson, thinking of the transmission of the plague bacillus by rat fleas, suggested regurgitation of the contents of the insect’s stomach into the wound stemming from the bite. Strickland, Swellengrebel, and Brumpt quickly ruled out the inoculative pathway. They allowed rats to be bitten by infected fleas but prevented contaminated excrement from contacting the skin either by sterilizing the skin or inserting a fine layer of gauze. No infection was observed.

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Since trypanosomes were found in the rectal bulb, one could assume that the contaminative pathway completed the cycle. In order to show that only the excrement was infectious, Strickland infected the rodent by having it swallow contaminated fleas mixed with its food. The rat infected itself naturally, either by eating its fleas or by licking. This procedure was all the more reliable because metacyclic trypanosomes have greater penetrating power than blood-borne trypanosomes. Using infected flea excrement, Brumpt contaminated young rats by depositing a small amount of infectious liquid in the animals’ eyes and on the mucous membranes of their mouths. When the same experiments were repeated with blood-borne trypanosomes, the results were negative. The mode of contamination depended on vectorial transmission but also on the usual pathway of intestinal parasites. When the rat licked itself, it picked up parasites from its coat. And since it also ate its fleas, the insects acted as passive intermediate hosts. The elucidation of the cycle of Trypanosoma lewisi led to revision of the cycle of Trypanosoma cruzi. In 1912, in collaboration with Piraja da Silva, Brumpt observed trypanosomal flagellates in the excrement of Triatoma megistus. In order to prove that this liquid was infectious, he injected it into the peritoneal cavity of young mice: Typical trypanosomes were then observed in their blood. A few months later, Brumpt described the complete cycle in the bug. The blood-borne parasites changed into the crithidial form and then back to the trypanosomal form in the hindgut. “In all cases, the ingested trypanosomes were transformed . . . into Crithidia. In this form they multiplied. . . . These Crithidia decreased in size and shed their blepharoplast, ultimately yielding true trypanosomes. . . . As the larvae of Conorhinus age, the number of crithidial forms decreases and the number of trypanosomes increases.”12 Brumpt’s earlier work on nonpathogenic trypanosomes guided his research. The evolution of Trypanosoma cruzi was comparable to that of trypanosomes in fish and frogs, for which leeches played the role of intermediate hosts. The flagellate, after multiplication by binary fission in the crithidial form, matured into the trypanosomal form. The bloodborne form was thus the starting point and the metacyclic form the culmination. Whereas Chagas had observed noninfectious crithidial forms and trypanosomal forms, Brumpt showed that they had to be linked together.

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Ultimately, Brumpt established that cannibalism and coprophagy were also modes of dissemination of trypanosomes in insects. This form of evolution of the parasite was more common than one imagined. Brumpt found it in most trypanosomes that evolved in the fleas of small rodents, such as hamsters, rabbits, dormice, and mice. For all these species of trypanosomes, the metacyclic forms were found in excrement and never in the salivary glands or proboscis. But what was the mode of transmission of Trypanosoma cruzi? From the beginning, Brumpt ruled out the inoculative pathway. When a guinea pig is bitten by infected bugs, no trypanosomes appear in its blood. Brumpt repeated this experiment on Cercopithecus ruber: “Two monkeys of this species were bitten, one by Conorhinus megistus with infectious droppings, the other by Cimex lectularius with equally infectious droppings, but neither contracted the disease.” Since metacyclic trypanosomes were observed in the rectal bulb, a contaminative pathway had to be considered. But a new problem arose. If the rodents were infected by eating their fleas or by licking, these modes of contamination had to be ruled out in cases of human infection. Brumpt thought that the Trypanosoma cruzi in the insect droppings might somehow penetrate the skin and become infectious that way. In support of this hypothesis was the fact that the parasite had significant powers of penetration, since it was able to enter tissue to form cysts. This hypothesis was not confirmed, however: Experiments with infected excrement deposited on the skin of a monkey and a rat proved negative, because the excrement dried out and the trypanosomes died. Hence the idea of contamination via the mucous membranes of the mouth was revived. A series of experiments was performed to show that the trypanosomes have considerable penetrating power: “Excrement of Conorhinus deposited in the mouth or rectum of suckling mice (consequently without skin abrasions) invariably produced infections.” Still attempting to verify this hypothesis, Brumpt deposited a few drops of excremental liquid from infected bugs on the conjunctive membrane of a monkey: “The excrement deposited on the eyeball of a very vigorous adult Cercopithecus ruber infected it, and the animal was dead within a month, as quickly as if it had been inoculated in the peritoneum.” The mode of contamination in humans had to be different from that observed in rodents. In rodents, the process of contamination was a

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consequence of an instinctive behavior: Rats remove their fleas by licking. In humans, in natural conditions, the contamination had to be accidental: “Furthermore, it is probably through the mucous membranes of the mouth that man is infected. Conorhinus generally bites the face. . . . After their meal, and often before the end of the meal, these insects evacuate considerable amounts of excrement, which can readily come into contact with the mucous membranes of the mouth and infect the sleeping victim.”13 A second series of questions concerned the clinical description of the disease. Was parasitic thyroiditis in fact a new morbid entity? Or did its symptoms merely correspond to the same goiter and cretinism observed in Europe? Perhaps Chagas had mistaken the latter for chronic forms of what he called parasitic thyroiditis. If so, symptoms of hypothyroidism such as myxedema and thyroid hypertrophy might not be part of the clinical picture of the acute form of Chagas disease. Once one concluded that a few autopsies of acute cases were an insufficient basis for describing the chronic forms of parasitic thyroiditis, there was no choice but to reconsider the whole clinical description of Chagas disease. The critique of the extrapolation from acute to chronic cases was not the main point, however. It was merely the negative aspect of what really proved to be crucial: a more refined account of the clinical anatomy of goiter and cretinism. What we see emerging is a medical theory that contradicted Chagas’s point by point. Chagas’s theory relied on correlations between symptoms of the disease and lesions of the thyroid gland and nervous system. This led to the identification of a range of clinical forms from the most benign (pseudomyxedema) to the most serious (mental retardation, cretinism). But now a new theory emerged, a theory that dismissed the forms of parasitic thyroiditis as pure illusions. The new theory took full account of the latest research on the pathological anatomy of cretinism and saw the morbid manifestations of hypothyroidism as a hereditary disease. In short, the new theory told a completely different story about the pathology Chagas had described: The various forms of parasitic thyroiditis could no longer be differentiated from goiter and cretinism; rather, they corresponded point by point. At worst, Chagas had passed off a clinical account of goiter and cretinism as a description of chronic parasitic thyroiditis—a regrettable case of confusion. At best, his description of the acute form of the disease had confounded the signs of two distinct maladies: He had superimposed two morbid entities, a parasitosis and the classic signs of hypothyroidism.

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Kraus immediately pointed out that the clinical anatomy of goiter in Minas Gerais was no different from the clinical anatomy of goiter as described in Europe: “The form and frequency of endemic goiter correspond perfectly with Chagas’s description. Even from a histological point of view, it is impossible to establish any difference.” Since cretinism is endemic myxedema, neither has any distinguishing clinical characteristic. This view of cretinism contradicted Chagas’s: There were no significant differences between cases of cretinism and myxedema. Disturbances of the intellectual faculties in cretins were highly variable: “In regard to intelligence, one observes the full range of gradations, from intact intelligence to the cretinoid, semi-cretinous, and absolutely cretinous state, the latter being indistinguishable from idiocy.” The same could be said about motor troubles: “Cretins present with all gradations from uncertain gait to total paralysis of the legs with contracture. In serious cases, Scholz tells us, victims can neither walk nor stand erect.”14 These states correspond to lesions of the thyroid gland: areas of atrophic sclerosis and spots of cystic degeneration. But one also finds lesions of the nervous system: Cretins exhibit organic disorders associated with meningoencephalitis. Finally, Kraus noted that cretins are often offspring of patients with goiter. He counted heredity among the primary factors in cretinism and pointed out that Fodéré had already found that where goiter runs in families, the incidence of cretinism is high. Recent research showed that goiter in mothers had a marked effect on their children. Kraus reported his own experiments on animals in conjunction with Ranzi and von Graf. Goats whose thyroids were removed in pregnancy produced stillborn offspring. This fine perception of the symptoms and lesions associated with cretinism guided revision of the clinical account of parasitic thyroiditis. Chagas had identified mxyedematous, pseudomyxedematous, and paraschizotrypanosomic (goiter, infantilism) forms of the disease. But if cretinism was merely myxedema in the endemic state, differentiating chronic forms of parasitic thyroiditis from cretinism and goiter was an operation doomed to failure. To be sure, Chagas had anticipated the objection, noting that the difficulty was more apparent than real: It was impossible to confuse the chronic forms of parasitic thyroiditis with cretinism, he argued. In Chagas disease, troubles of the intelligence were not as marked as in cretinism. In serious cases, moreover, troubles of the intelligence (idiocy, dementia, and imbecility),

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often associated with problems of mobility, were due to lesions of the nervous system. For Kraus, these differences, based in part on symptomatology and in part on pathological anatomy, were irrelevant because troubles of the intelligence and mobility can be minor in some cretins, while more serious cases exhibit cerebrospinal lesions. Kraus thus cast doubt on Chagas’s whole account of the chronic forms of the new nosological entity. For him, these were simply classic endocrine disorders: “In contrast to Chagas, who wants to differentiate goiter and endemic cretinism from the chronic clinical manifestations of Brazilian trypanosomiasis, it is observed that the form and frequency of endemic goiter correspond to Chagas’s description of chronic cases.”15 But what about the clinical description of the acute infection in very young children? For Chagas, the acute phase of the disease was characterized by a specific set of symptoms: hypertrophy of the thyroid, myxedema, fever, and swollen lymph nodes. Once Kraus associated the chronic forms of parasitic thyroiditis with goiter and cretinism, he did not doubt that the Brazilian doctor had confused these disorders with his account of acute parasitic thyroiditis. The idea that the acute form of Chagas disease was complicated by concomitant goiter and cretinism seemed inescapable: “As for certain isolated symptoms such as goiter and myxedema found in these same cases, which the author also attempts to link to the same parasitic cause, it might well be necessary to ask whether endemic goiter and myxedema are not mere complications.” Chagas had considered this possibility but had ruled it out because breastfed newborns always presented with signs of hypothyroidism. By refuting the hydric and microbial etiologies of thyroid insufficiency, Chagas thought he had proved that hypothyroidism was linked to the parasitic invasion. For Kraus, however, this argument carried no weight because one could invoke the hereditary factor: “Chagas’s assumption that children who drink no water cannot acquire endemic goiter is not very persuasive, because goiter and cretinism can be transmitted from parent to child.” Although Kraus never for a moment doubted the causal relationship between the trypanosome and the parasitosis, he was also convinced that Chagas’s clinical account confused two different diseases. He therefore began to pick Chagas’s theory apart: From the acute form described by Chagas, one had to eliminate the symptoms of goiter and cretinism.

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After subtracting myxedema and thyroid hypertrophy, Kraus proposed a new definition of Chagas disease: “The acute form of the trypanosomiasis must be a disease sui generis and probably has no relation to thyroid hypertrophy or endemic myxedema. The acute form, which is characterized by acute symptoms such as fever, generalized swelling of the lymph nodes, and above all the characteristic results of blood testing, which alone permit a diagnosis, might later differentiate it easily from endemic goiter.”16 A third series of questions arose for epidemiologists who rejected the diagnosis of parasitic thyroiditis. When patients in regions where infected insects were prevalent presented with signs of thyroid insufficiency, were they victims of parasitic thyroiditis, or were they exhibiting classic forms of goiter and cretinism? If, as Kraus believed, Chagas had confused parasitic thyroiditis with goiter and cretinism, one would need to look for cases of Chagas disease in regions infested with insects but without goiter. As soon as it was recognized that the clinical account of parasitic thyroiditis might mistakenly include signs of goiter and cretinism, it became clear that Chagas had failed to take the precautions necessary to place his epidemiological study above suspicion. But that is not the key point. The main difficulty was the lack of a reliable method of diagnosing Chagas disease. Because the observation of Leishmanian forms in the tissue of experimentally infected animals was one sure sign, a new epidemiology was developed in opposition to Chagas’s method. Chagas had pointed not only to a correlation between contaminated insects and chronic forms of the disease but also to a diagnostic method based on locating schizogonic forms in the lungs of experimental animals inoculated with blood from patients. A new experiment was devised in which the coincidence of infected bugs with pathological forms was a necessary condition of the disease but not a sufficient one. It was an experiment in which the parasitic etiology of goiter and cretinism was subjected to a conclusive test: one that would reveal, in the absence of parasites, the presence of Leishmanian forms in laboratory animals infected with the blood of suspect individuals. When Kraus applied this reliable new diagnostic test, he noted a gap where Chagas had seen a causal relationship. There was no connection between infected insects and supposed chronic forms of parasitic thyroiditis. In other words, Chagas’s description of the chronic forms of his disease coincided with the description of goiter and cretinism as observed in both

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Europe and Argentina. Kraus did not doubt the existence of the acute forms of the disease that Chagas had identified by observing parasites in the blood. But in Argentina it proved impossible to find acute forms in areas where the insect was abundant. We must pause briefly to recall one of the practical applications of Chagas’s initial theory of the life cycle of the parasite. Because he believed that the sexed forms of the parasite were the infectious forms, he also believed that inoculation of laboratory animals with blood from patients would always lead to gametogony in the lungs. This led to the idea that the chronic forms of American trypanosomiasis could be diagnosed by examining lung smears from experimental animals. “This microscopic diagnostic procedure works for most chronic cases, in which the parasite cannot be found in the blood. Inoculated guinea pigs die after a variable length of time, and parasitic forms are found in their lungs.”17 In 1911, Chagas announced the identification of sixteen acute cases: The parasite was found in the blood of these patients. As for the chronic forms of the disease, the other diagnostic procedure yielded positive results in 40 percent of the cases: 100 cases out of a total of 232 patients. As noted earlier, however, Chagas mistook an infection by an accidental parasite for gametogony. His identification of chronic forms by this method was thus totally discredited. Kraus therefore had good reason to doubt the authenticity of the chronic forms of parasitic thyroiditis. Not only had Chagas confounded the chronic forms with goiter and cretinism, but his diagnostic method was also invalid. In order to identify the disease, it would be necessary to revert to Koch’s postulates. For the acute form, this meant observing the parasite, and for the chronic forms, it meant inoculating experimental animals with the blood of patients and looking for Leishmanian forms in the organs. With these new criteria, it was no longer possible to link the chronic forms of the disease to a distinctive clinical account (with diagnosis based on supposed gametogony and geographic coincidence of infected insects with goiter). The epidemiological investigation led by Kraus was intended to answer a question that Lozano had raised after returning from Rio de Janeiro. Did goiter and cretinism in Argentina correspond to the endemic forms observed in Europe, or were these signs of insect-transmitted Chagas disease? In order to confirm or refute the hypothetical causal relationship between infected insects and chronic forms of parasitic thyroiditis, infected insects

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first had to be located. A medical entomological study was therefore initiated. With the cooperation of rural doctors, Maggio and Rosenbusch collected specimens from various parts of Argentina. Most of the insects turned out to be contaminated with the parasite. In 1914, they mapped the distribution of the insect along with various indices of infestation. Bugs from northern and central Argentina contained trypanosomes in their guts that could be transmitted to laboratory animals. The Leishmanian form was detected in the heart and striated muscle of these animals. In that same year the two scientists published the results of blood analyses of thirteen patients, six of whom exhibited chronic goiter along with idiocy (adults) and seven chronic goiter (children from nine to thirteen years of age). “In none of these cases did we find parasites either in direct examination of the blood or in inoculated guinea pigs. With so few cases, we cannot say that the disease does not exist in this country.”18 In 1916, Maggio and Rosenbusch were able to publish the results of a vast survey of cases of goiter and cretinism in various public institutions (hospitals, asylums, schools, and maternity hospitals) located in regions where insects were prevalent. They examined the blood of patients and inoculated guinea pigs in order to look for cysts in their organs. All results were negative. Unable to perform autopsies, which would have enabled them to identify (or not) Leishmanian forms in tissue, Maggio and Rosenbusch applied a principle of comparative pathology. They conducted autopsies of goiterous animals in Argentine slaughterhouses: No Leishmanian forms were found. “In the Argentine republic, there are regions with infected insects, in which endemic goiter and cretinism exist, but thus far it has proved impossible to characterize these as chronic forms of Chagas’s trypanosomiasis.”19 It was the existence of areas infested with infected insects but without obvious goiter or cretinism that led Rosenbusch to undertake further research. “Everyone in the population with suspect symptoms was subjected to careful examination of the blood, always with a negative result. . . . In the village of Cachi we found some individuals with slightly enlarged thyroid glands. . . . Clinical examination of families in Cachi . . . did not reveal the presence of goiter, but in children we observed a slight facial edema (very common throughout Salta) and in some cases signs of micro-adenopathy. . . . In children in the schools of Palermo, La Poma, and El Trigal we see slight swelling of the lymph nodes. Examination of the blood was negative in all cases. Some subjects presented with a facial edema.”

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To us, it is clear that Rosenbusch was looking at cases of American trypanosomiasis, but we can also understand why he failed to see them. The absence of prominent goiter or cretinism and the presence of infected insects no doubt created a situation favorable to the identification of Chagas disease. But Rosenbusch’s idea of the pure form of the disease stood as the major obstacle to such identification. In the acute form of Chagas disease, one would not expect to observe myxedema and thyroid hypertrophy because these are signs of thyroid insufficiency. Although Rosenbusch was working in an area where goiter and cretinism were not prevalent, his clinical conception of the disease was that it was an expression of a benign form of hyperthyroidism: “Slight enlargement of the thyroid gland . . . slight facial edema in children . . . edema of the face.” Rosenbusch failed to grasp the fact that he was confronting the pure forms of Chagas disease, especially since examination of the children’s blood revealed no sign of the parasite. Nor did he imagine that his negative findings might not have the value he attributed to them without the slightest hesitation. His conclusion leaves no doubt as to the way in which he perceived the enlarged thyroids and edemas. For him, these morbid signs were expressions of hypothyroidism: “From these observations it follows logically that the high percentage of infected Triatoma infestans Klug plays no role in the production of goiter and cretinism” in northern Argentina.20 Rosenbusch then shifted his research in another direction. Having ruled out a deficiency of iodine in the drinking water, which had exactly the same content in the areas of endemic goiter as elsewhere, he raised the possibility that the water had been contaminated with a germ stemming from affected individuals. Curiously, the threefold critique of Chagas’s medical system did not lead to an epistemological reorganization of the disease. Biologically speaking, the revision of the life cycle of the protozoon led to the discovery of the contaminative pathway. But Brumpt did not question the clinical account of Chagas disease. The relation between the parasitology and the clinical description of the disease involved two independent but tightly related modes of interpretation. Parasitology studied the trypanosome from a biological point of view, whereas clinical medicine looked upon the parasite as an etiological agent responsible for certain endocrine disorders. Despite differences of opinion as to the mode of transmission, Brumpt and his contemporaries therefore agreed with Chagas that the signs of hypothyroidism were the result of thyroid disorders due to the etiological agent. The study

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of how the parasite was transmitted remained independent of examination of symptoms associated with the contaminative pathway. Something like a clinical account of a form of parasitosis remained unexplored. Subsequently, examination of the clinical descriptions of parasitic thyroiditis revealed a twofold disagreement: Where Chagas had seen chronic forms of parasitic thyroiditis, Kraus saw goiter and cretinism, and where Chagas described the acute form of the disease, Kraus saw signs of two different diseases. The difference between Kraus and Chagas was at once enormous and tiny. Enormous, in that Chagas tied signs of thyroid insufficiency to parasitic thyroiditis, whereas Kraus linked them to goiter and cretinism. Tiny, because despite their differences of opinion as to the nature of the nosological entity, they agreed in seeing signs of hypothyroidism. This agreement, to reiterate, ruled out something like a clinical account of a parasitosis. Finally, the epidemiological studies of Kraus, Maggio, and Rosenbusch refuted the parasitic theory of goiter and cretinism. Hence they were forced to link all the symptoms of hypothyroidism to a hereditaryinfectious etiology. Despite differences of opinion as to the causal factor of the endemic, Kraus agreed with Chagas in seeing an endocrine disorder. Kraus immediately linked his view of the etiology of goiter and cretinism to the way in which one ought to think about Chagas disease. In Brazil, and in the acute form only, the signs of an endocrine disorder could mask a parasitosis. Kraus here challenged the causal link, not between infected insects and a form of parasitosis, but between the insects and the signs of hypothyroidism that hid the parasitosis. For the third time, the clinical description of a parasitosis was in a sense ruled out, as it were, by definition: Because there was no myxedema or hypertrophy of the thyroid, there could not be any facial swelling associated with the new disease.

A Closed Arena The first Pan-American Medical Congress was held in Buenos Aires in 1916. Chagas gave a lecture on American trypanosomiasis: “We have followed the work of Kraus, Rosenbusch, and other Argentine scientists on this subject with sincere pleasure. Thanks to the certainty of their method and impressive technical and observational capabilities, we hope they will discover the ultimate truth about questions that our own work has left unresolved.”21

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There was no irony in this homage. Chagas had understood Kraus’s criticisms so well that he was already perfecting his medical system. He modified the clinical description of the acute form: Thyroid hypertrophy, which had been considered a dominant symptom, vanished. Some of the chronic forms, which had been challenged, were eliminated: The pseudomyxedematous form lacked specificity; the mxyedematous form introduced confusion with infantile myxedema; and the chronic forms with acute exacerbation pointlessly recapitulated the acute form. But Chagas’s concessions ended there. On the whole, he hardened his position. Against Brumpt he defended the hypothesis of sexual dimorphism and its correlative, the inoculative pathway. To rule out any possibility of contamination by excrement, Magarinos Torres had infected animals via insect bites. And guided by an analogy with the fertilization of a free parasite, Prowazeckia cruzi, Chagas thought he saw the same thing in insects: “Development begins with fertilization between two forms of the parasite in the midgut of the hematophage and ends subsequently in the salivary glands.”22 Against Kraus he argued that his description of the acute form did not mix up two different diseases. The sudden appearance of myxedema, along with its rapid evolution and intensity, sufficed to distinguish the acute form of Chagas disease from any other manifestation of hypothyroidism. “A few days after the onset of fever, the patient begins to swell. He swells up, his face is full, his eyebrows are tumescent, his lips are thick, his tongue is thick and pasty. . . . Indeed, myxedema is so salient a sign that it permits clinical diagnosis at a distance.”23 In the chronic forms, the syndromes of the acute forms could evolve toward acquired infantile hypothyroidism (arrested development, mental retardation) or toward adult goiter in Minas Gerais. Finally, Chagas stood by his parasitic theory of goiter and cretinism. In 1915, he ruled out the hydro-telluric theory, which attributed goiter to organic or inorganic chemical substances originating in the soil and transmitted by water. He also refuted the infectious theory: In a region where everyone drank the same water, hypothyroidism was seen only in individuals who lived in cottages. As for heredity, it played no role: Individuals from areas unaffected by goiter contracted the disease as soon as they moved into bug-infested homes. In his scientific debate with Kraus, Chagas rejected the idea of hypothyroidism due to a hereditary-infectious etiology. Parasitic thyroiditis was incompatible with the classic forms of hypothyroidism. Not entirely

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incompatible, however. In 1915, Chaves attempted to reconcile the two. The hereditary factor could lead to diminished functional capacity of the thyroid (miopragia), but it was the parasitic infection that led to the emergence of an endocrine disorder. In other words, infection by the parasite turned a latent disorder into a manifest one: “The hereditary predisposition might then aggravate the condition of patients infected with trypanosomiasis and facilitate the explosion of generalized myxedema and other signs of thyroid insufficiency in cases where the infection encounters a condition of hereditary miopragia.”24 This hypothesis made it possible to relate the hereditary factor to the local factor associated with trypanosome infection, but it was at once embarrassing and seductive. Embarrassing, because it revived the idea of a hereditary endocrine disorder. Seductive, because it reinforced the idea of a causal relationship between the parasite and myxedema. Chagas’s ambivalence toward this hypothesis tells us something about the way in which he saw the most salient sign of his disease. On the one hand, he rejected the idea of hereditary miopragia. If a latent thyroid insufficiency existed, it still had to be actualized by another disease: “Against this purely theoretical reasoning, we point to the absence of aggravation of this glandular miopragia by other diseases common in the region (malaria, ankylostomiasis, pneumonia, and exanthematic fever), because it allows us to consider hypothyroidism as a phenomenon, etc.”25 On the other hand, he did not reject this specific pathological hypothesis concerning trypanosomiasis: “If the trypanosomian infection played no other role than to reveal the preexisting miopragia of the gland, one would have to acknowledge that the parasite acted in some specific way on the thyroid.” This was the only explanation, moreover: “One cannot reasonably understand the physiopathological phenomena of the acute cases without acknowledging the specific action of the infection on the thyroid gland.”26 Chagas’s position was at once close to Kraus’s and diametrically opposed to it. Close, because they agreed that myxedema was the expression of hypothyroidism. Diametrically opposed, concerning the cause of the thyroid disorder: either it was the parasite, in which case you had parasitic thyroiditis, or it was a hereditary-infectious etiology, and you had the classic forms of goiter and cretinism. Chagas and Kraus thus defined two experimental paradigms that would orient the research of their contemporaries. Epidemiology had only two

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ways of conceptualizing the unity of a causal agent and a pathological entity. One procedure was tantamount to a system of double-entry bookkeeping: One could start by detecting a parasite in the blood of a patient and then work backward toward the infected insect, or one could start with an infected insect and work forward toward blood testing of suspect individuals. Then and only then could one claim that a clinical description was in fact a description of the symptoms of parasitic thyroiditis. Although it might be tempting to identify new cases of the disease, such identification had no epistemological significance. One would search in vain for clarification of Chagas’s account of the various pathological forms of his disease. His differential diagnoses were always modeled directly on his descriptions: Signs of thyroid insufficiency recur repeatedly. But epidemiology could also be invoked to show that a suspected causal relation between infected insects and parasitic thyroiditis was in fact an illusion. The method in this case was to look for the pathological entity described by Chagas in areas where infected insects were prevalent. The absence of parasitic thyroiditis in such areas would then suggest that this particular morbid entity was nonexistent. In this period, both proponents and adversaries of Chagas disease were guilty of hasty generalizations. Proponents pointed to a small number of patients, to areas infested with infected insects, and to doctors’ reports of goiter as indications of a widespread scourge. Adversaries pointed to the absence of disease in areas where infected insects were common and to contradictory medical reports to reach the opposite conclusion: Parasitic thyroiditis was rare and perhaps even nonexistent. The first identification procedure involved incidental encounters with patients. Individuals consulted with physicians because they suffered from a malady that was common in Latin America. In El Salvador in 1913, Segovia saw a patient with malaria and found trypanosomes in his blood. “Our case appears to be related to the pseudomyxedematous form, but we found no hypertrophy of the thyroid gland, no splenomegaly, and no adenopathy.”27 In Peru in 1919, Escomel saw a patient who complained of venereal disease. He came from a region where Triatoma megista was common: “This examination allowed us to observe the existence of the trypanosome. . . . The eyelids, limbs, and rest of the body exhibited hard edema that resisted finger pressure. . . . The edema rather belonged to the category of myxedemas.”28

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But one could also start with infected insects and then look for parasites in the blood of individuals exposed to it. Areas of the state of São Paulo were infested with triatomae of the megista, infestans, and sordida species. In Brotas, Maciel inoculated a guinea pig with the blood of a child and found Leishmanian forms in the animal’s muscles. In Ribeiro Preto, Bayma also found Leishmanian forms after inoculating an animal with blood from a child presenting with a small goiter. In 1918, Villela learned of the existence of Triatoma megista in a rancho in São João de Bõa Vista and proceeded to identify the parasite: “A child of sixteen months, whose thyroid was not appreciably enlarged, presented with a swelling exhibiting the characteristics of myxedema.”29 In 1919, Tejera systematically examined the blood of fever patients in an era where Rhodnius prolixus was common. He found three patients and described the usual symptoms: facial swelling, edematous eyelids, swollen lymph nodes, and thyroid hypertrophy. Soon thereafter, Neiva applied a form of natural xenodiagnosis: Insect infestation was the only sign. Examination of the contents of the gut of the triatomae became an indicator of the local morbidity due to Trypanosoma cruzi: “More rapidly than any other procedure, this will reveal the presence of Chagas disease in affected areas.”30 Endemic goiter and cretinism in insect-infested regions offered a complementary argument. In Paraguay and the state of Rio Grande do Sul, a scientific mission composed of Lutz, Souza Araujo, Migone, and Fonseca found infected insects. Local doctors attested to the existence of Chagas disease, that is, of patients with goiter. In the same region, using the same method, Oliveira and Souza Araujo came to the same conclusion. The other procedure was to observe the presence of infected insects but the absence of disease. In the state of Bahia, numerous infested areas were identified, but local doctors, medical school records, and public health reports all failed to mention any sign of Chagas disease. In the state of Rio Grande do Sul, results were also negative: “No authentic case of American trypanosomiasis is known to exist in Rio Grande do Sul, where these bugs are widespread in more than half the territory.” In the state of Ceara, Parreiras Horta found Rhodnius prolixus but no mention of Chagas disease: “The triatomae and Rhodnius in the state of Ceara are also infected. I obtained reports of the Rural Public Health Service pertaining to morbid entities in Ceara but found nothing.”31 In Brazil, Chagas’s adversaries came to the same conclusions as Kraus. There was one difference, however: Kraus

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thought that the disease did not exist in Argentina, but he readily acknowledged its presence in Brazil, although in combination with cretinism. In his eyes, the parasitological diagnosis constituted irrefutable proof. For Parreiras Horta, the presence of the parasite in the blood or of Leishmanian forms in tissue had no etiological significance. To reach that conclusion, it sufficed to apply the hypothesis that Kraus had proposed to explain the absence of the disease in Argentina despite the presence of infected insects. He suggested an attenuation of the virulence of Trypanosoma cruzi due to the climate. Parreiras Horta drew a parallel between Trypanosoma cruzi and harmless animal parasites, and between Leishmanian forms and a nonpathogenic livestock parasite found in cardiac muscle, Sarcocistis bulbali. This led him to the following assertion: “Nearly all of America, from Argentina, Paraguay, and Uruguay to the United States, is full of infected insects. In the human medical literature, there are only a few cases other than those reported by Chagas.”32 Chagas’s few cases were the exception that confirmed the rule. Aragão, relying on Parreiras Horta’s investigations, drew all the conclusions from his findings: Not only was there no causal relation between infected insects and goiter, but when the trypanosome was found in goiter patients, it was a harmless incidental parasite. Aragão thus reverted to the infectious etiology of endocrine disorders: “Among other hypotheses, one that has appeared recently is that the disease is due to a filterable virus. . . . I regard the hypothesis of a trypanosomic origin as absolutely untenable.”33 Three problems remained in suspense. In regard to the mode of transmission, proponents of the inoculative pathway clashed with proponents of contamination via the mucous membranes of the mouth. The clinical description of the disease was not settled. Instead of parasitic thyroiditis, some saw an endocrine disorder, or, at best, two combined diseases, one of which (goiter or cretinism) was known, while the other was indeterminate (American trypanosomiasis). The causal relationship between infected insects and endemic goiter and cretinism was countered by a hereditaryinfectious etiology. All of these disagreements stemmed from a single blind spot. To us, the shift in meaning and conceptual level is obvious, but the difference between the sign of a parasitosis (palpebral edema) and the sign of hypothyroidism (myxedema) was invisible to doctors at the time because of the way in which

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the pathogenic mechanism was deciphered. The epidemiological studies are interesting not for what they allowed physicians to see but rather for what they hid and what they revealed. On the one hand, they hid a pathognomonic sign linked to the mode of contamination; they obscured the fundamental fact that would later lead to the classification of Chagas disease as a type of parasitosis by severing the tie to endocrine pathology. On the other hand, they revealed facial swelling as a sign of thyroid insufficiency, which some attributed to a parasitic thyroiditis and others to an endocrine disorder. At this point, and for fifteen years to come, what was reported as “facial swelling” was interpreted as myxedema. Myxedema is compatible not only with the symptoms of parasitosis (fever, splenomegaly, hepatomegaly, adenopathy) but also with those of hypothyroidism (thyroid hypertrophy, idiocy, infantilism). The result was, as we have seen, a series of superficial conflicts, in which no serious epistemological issue was at stake. The historians who say that Chagas’s resistance to his detractors was totally justified and that he was right and they were wrong are suffering from a retrospective illusion. If one wants to play this little game, then one has to admit that Kraus’s attacks on Chagas were also totally justified and that Kraus was right and Chagas was wrong. But that is not the point: In this period, no one was capable of distinguishing between distinct but superimposed morbid entities. The pure form of Chagas disease could not be seen for the simple reason that it had yet to be constituted as a distinct morbid entity.

Conflicting Interests The events are well known. On November 30, 1922, Vasconcellos was received as an honorary member of the National Academy of Medicine. Following the welcoming speech, Peixoto launched a violent attack on Chagas, “the inventor of a rare and unknown disease, about which much has been said but no patients have been seen” and which supposedly affected millions of Brazilians, who were “accused of being cretins.” Worse, Chagas was charged with having initiated a costly but pointless reform to deal with an imaginary plague and of “having done everything that unscrupulous vanity and provocative impudence can imagine.”34

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Chagas immediately dispatched two letters to the president of the academy, Miguel Couto. In the first he asked that a commission be appointed to assess the value of his work and offered to resign if his findings were discredited. In the second, he listed his demands. It was time to settle the issue of his role in the discovery and to ascertain the extent of the disease: “Is or is not the extent of the new disease in the interior of the country a social problem of the highest order, deserving of the attention of the government and the diligence of public health officials?”35 Peixoto also sent two letters. He toned down his accusations but persisted in saying that the “Lassance malady” (some forty cases) was not as important as some would make it out to be. He also called for a reexamination of the question. Peixoto’s initiative was hailed by Azevedo Sodré as courageous and useful. The issue was the parasitic etiology of goiter. If goiter was indeed a symptom of Brazilian trypanosomiasis, the scourge was indeed vast. But if it was not, then Chagas disease was a mere pathological curiosity, and there was no need to mobilize the public health authorities. An investigating commission was appointed. It consisted of Alfredo Nascimento, Henrique Duque, Mac Dowell, Parreiras Horta, Eduardo Meirelles (who resigned a week later), and Artidonio Pamplona, who was soon replaced by Moreira da Fonseca. Fraga, Fonseca, and Couto represented Chagas. Vasconcellos, Parreiras Horta, and Fontes spoke for Peixoto. A year later, the commission delivered its findings. On the whole, they were favorable to Chagas. But the commission was unable to settle the issue as to the parasitic etiology of goiter. Chagas then took his defense to the National Academy of Medicine: The memorable session of December 1923 made headlines. The attacks had begun much earlier, however. The academy debate followed on the heels of another controversy, which began in 1919 at the Rio de Janeiro Society of Medicine and Surgery. On the day Aragão was received as a member, Vasconcellos had charged Chagas with taking credit for a discovery actually made by Cruz. He also accused Chagas of errors and of promoting belief in the existence of a deadly endemic. It was no accident that Vasconcellos, Fontes, and Aragão were among Peixoto’s supporters. All of them nursed an old grudge against Chagas. It all went back to a competition for the post of department head left vacant by the departure of Rocha-Lima in 1911. Chagas had been favored over these

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other candidates. From that point on, all of the young Brazilian doctor’s efforts seemed crowned with success. His rise was meteoric. In 1917, he succeeded Cruz as head of the institute and reinvigorated the public health movement through the League for a Healthier Brazil. In 1919, he was named director general of public health. The following year, he dreamed of an even higher distinction, as can be seen from the publication of a pamphlet entitled Exposition of Reasons for the Presentation of Dr. Carlos Ribeiro Justiniano das Chagas as a Candidate for the Nobel Prize in Medicine (1920). Nor was it an accident that the polemic erupted after 1917. Not only was Cruz no longer there to quiet dissension, but Kraus’s work had cast doubt on what had seemed to be settled results. This setback was enough to trigger a reconsideration of all aspects of the history of Chagas disease: discovery of the parasite, ensuing experiments, and more recent epidemiological surveys. New knowledge of the disease seemed to lay Chagas’s work open to criticism. But make no mistake: The violent attack on Chagas was a work of revenge. Doubt was cast on Chagas’s professional competence, on the legitimacy of his power, and on the ethics of his behavior. Scientific criticism was combined with attacks of an extrascientific order. The latter must now be described. Vasconcellos claimed that his motive for revisiting the history of the discovery of Trypanosoma cruzi was a disinterested one: “If I am looking at the question again, it is for the sole purpose of restoring the historical truth.”36 It would be wrong, however, to take this statement at face value. His whole historical analysis was based on the proposition that credit for a discovery should go to the discoverer. His narrative seizes on the relation between gaze and object, and his demonstration depends on an order of things from which thought is banished. What interests him is not the history of scientific thought but that of a scientific object supposedly given by nature. To know is to discover: For Vasconcellos, seeing the trypanosome was the essence of the discovery. That is why Vasconcellos attached such importance to evidence that to him seemed decisive. And to begin with, the evidence of his own eyes. If the discoverer of a thing is the first person to see it, then to see the person who sees is to offer irrefutable proof. Vasconcellos reports the experimental infections performed by Cruz in Manguinhos as follows: “The glory of having seen this protozoon for the first time and therefore for having

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discovered it belongs to Oswaldo Cruz. . . . I was an eyewitness to the way in which the parasite was discovered, and I believe it is my duty to restore the truth and to credit [Cruz] with this service to science, credit he undeniably deserves.”37 In addition to Vasconcellos’s eyewitness testimony, there was the testimony of medical authorities. Vasconcellos quotes a lengthy excerpt from a lecture by Fraga, who was one of the first to propose that the new malady be called “Cruz and Chagas disease” (1912). Vasconcellos also quotes from a lecture by Cruz. Why did Cruz not say that Chagas had discovered Trypanosoma cruzi? Because he himself was the discoverer. Finally, Vasconcellos subjected all of Chagas’s publications to critical scrutiny. This was easy game, because Chagas had told many versions of the story, and his accounts were full of contradictions. Indeed, on occasion he let the truth slip out. In his “Preliminary Note,” dated December 17, 1908, Chagas clearly stated that Cruz had caused the monkey to be bitten by the insect and that “he [subsequently] found” trypanosomes in the animal’s blood. A disinterested motive was also claimed for revising the history of research following the discovery of the parasite. The Manguinhos scientists deserved credit for their decisive contributions: “In all justice they deserve a share of the glory. They were not mere assistants but intelligent collaborators, who did original research to shed light on the disease, things that would never have been learned without them.” Note in passing that Vasconcellos hints at what he thought of Chagas in describing the attitude of Cruz: “Blessed with enormous altruism, unparalleled goodness, and a great and generous soul, Oswaldo Cruz drew on his own wealth to give to others, making it a matter of principle that his name did not appear lest he overshadow and diminish the contributions of those who worked with him.”38 It would be wrong, however, to think that it was a concern with fairness that led Vasconcellos to revise the history of the discovery. His entire historical analysis was based on the postulate, complementary to the previous one, that there is no science without truth. Hence error belongs to the realm of fantasy. It is the assertion of a fact that does not exist and therefore cannot be observed. His history is not a history of error but rather of the vain presumption of the person who commits the error. That is why he was so interested in research that discredited Chagas’s findings, and in particular the discovery due to his “illustrious colleague Henrique Aragão.”

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It should now be clear why Vasconcellos attached so much importance to Aragão’s observations, which showed that the pulmonary forms that Chagas had included in the life cycle of Trypanosoma cruzi were actually forms of a different parasite: “Dr. Chagas managed to see all these vital phenomena under his microscope! Dr. Chagas saw the merozoites separate, enter the blood stream, penetrate the blood cells, develop, and exit. . . . But none of this ever existed! I cannot understand, Mr. President, how Dr. Chagas could have had the audacity to assert the existence of a scientific fact, which even hypothetically he could not have observed!”39 Vasconcellos then went on to point out the consequences of this error: It formed the basis for diagnosis of the chronic forms of the disease and therefore for the confusion with endemic goiter. Finally, Vasconcellos presented his critique of the parasitic theory of goiter as a humanitarian gesture. To suggest that a terrible scourge existed in Brazil was to discredit the nation, discourage immigration, and denigrate the Brazilian people. “My reasons for thinking as I do are, I assure you, not dictated by any petty interests but solely by patriotism and a sincere desire to serve our cherished fatherland.”40 It would be a mistake, however, to take at face value Vasconcellos’s claim that his motives were benevolently philanthropic. He pursued two lines of attack. The first was legitimate though not original: The scientific critique of Chagas had already spread beyond the bounds of the scientific community. For example, on August 17, 1920, the newspaper La Noite published an article criticizing Chagas’s “exaggerations” on the basis of a recent paper by Kraus titled “Chagas Disease in Argentina, Studies and Observations by Professor Kraus.” Once it was recognized that Chagas disease did not fit the classic profile of vectorial diseases (such as yellow fever, malaria, and sleeping sickness), its reality began to be questioned. One had a parasite and a vector, but no disease was in sight. The second line of attack was insidious, because it turned scientific criticism into slander. The tenor of Vasconcellos’s critique changed when he began to question Chagas’s motives, alleging that Chagas had deliberately fostered ambiguity as to the nature of the disease for the sole purpose of furthering his ambitions in the area of public health policy. By exaggerating the danger and prevalence of parasitic thyroiditis, which he portrayed as one of the major public health dangers facing Brazil, Chagas had allegedly lent credence to Miguel Pereira’s famous remark that “Brazil is one

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vast hospital.” Chagas, Vasconcellos charged, held out the utopian prospect of national redemption in order to acquire advantage, prestige, and power. By downgrading the importance of American trypanosomiasis, Vasconcellos hoped to further his own career. Claiming that the disease was at best rare if it existed at all, Vasconcellos placed himself in the camp of optimists, in contrast to the pessimist Chagas. Despite his undistinguished scientific record, Vasconcellos thus cast himself in the role of expert on medical ethics, not to say public morality. Chagas quickly responded to his detractors. In the historical account he gave in 1922, he implicitly credited the discovery of the parasite to his teacher but showed that this was not the whole story. Following Cruz, he placed the discovery of a novel pathology at the beginning of the saga: “Something new in the realm of pathology remained unknown and did not yield to our curiosity.” But it was Cruz who had infected a monkey and discovered the pathogenic trypanosome. The narrative of the laboratory phase of the work attested to this. In order to avoid misunderstanding, one has to take the verb “verify” in its literal sense, as Chagas intended it. Chagas first verified the presence of Trypanosoma minasense, which had been discovered in Minas Gerais. Then, after staining the parasite, he corrected his initial mistake: “I thus verified that the observed trypanosome was morphologically different from Trypanosoma minasense.” Chagas concluded his account with these words: “This is the exact truth concerning the discovery of Trypanosoma cruzi.” And no doubt it was, provided we add that Chagas verified Cruz’s observation of the pathogenic parasite in the monkey. What followed proved that Chagas did not conflate discovery with verification. The return to Minas Gerais was marked by the discovery of the pathogenic parasite in a patient and verification of the disease. To be sure, the pathogenic parasite found in Berenice was the same as the one that had been observed in the laboratory monkey. But it was also different, because a natural infection differs from an experimental infection as pathology differs from protozoology. That is why Chagas speaks here of “the discovery of Trypanosoma cruzi in man” and of “verification of the new disease.” Not only had a novel pathology been discovered initially, but the discovery of the pathogenic parasite in Berenice could be counted as a verification: “I turn now to an account of the discovery of Trypanosoma cruzi in man and to the verification of the new disease.”41

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More serious was Vasconcellos’s accusation that Chagas had appropriated the work of his collaborators. In 1922, Chagas paid homage to their efforts: the entomologist Neiva, the pathological anatomist Vianna, and the clinician Villela. But Chagas was well aware that Vasconcellos’s criticisms, unlike those of Parreiras Horta, which he took the trouble to refute, were merely a pretext for casting doubt on his intellectual honesty. That is why he ended his lecture to the Academy of Medicine with an impassioned protest: “I have neither defamed my country nor denigrated the native qualities of my race: a strong and valiant race, which has confronted with rare stoicism the maladies that afflict unfortunate regions of our land. . . . I do not want to be seen by my contemporaries as a person who, under cover of nationalism, made use of his compatriots. This would be contrary to the national interest and erect an obstacle to its civilizing impulse.”42 To appreciate the nature of this polemic as well as the stakes, one must go beyond the high rational principles invoked by Vasconcellos: truth, justice patriotism. Vasconcellos had three objectives: to show that Chagas deserved no credit for the discovery, that his power over his collaborators was usurped, and that his behavior was dictated by ambition. In regard to the science, Vasconcellos credited Cruz with the discovery, played up the contributions of the Manguinhos scientists, and showed that the disease was rare. By showing that Chagas had not discovered the parasite, that he had made errors, and that he had mistakenly included goiter among the symptoms of the disease, Vasconcellos sought to sully Chagas’s scientific reputation. With respect to power, Vasconcellos suggested that Chagas had appropriated his teacher’s discovery and his disciples’ research and had concocted an imaginary scourge. Vasconcellos thus tried to undermine Chagas’s legitimacy, which was based on his discovery of the parasite, his subsequent research, and his plans for combating the endemic. In the realm of ethics, Vasconcellos sought to demonstrate that Chagas had claimed credit for a discovery he had not made, concealed the work of his collaborators, and fostered imaginary fears by promoting the idea of a lethal plague. Vasconcellos alleged that Chagas’s behavior had been unethical: He had lied, dissimulated his debts to others, and unscrupulously denigrated his compatriots. Oswaldo Cruz had been quick to honor Chagas’s work, however. He had made his student’s name a symbol of the excellence of Brazilian medicine, identified Chagas’s findings with his own institute, and used the newly

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identified endemic to promote a project of public health. Ten years later, Vasconcellos tried to undo what Cruz had begun by demystifying the history of the disease. Although his attack was based on scientific argumentation, it had nothing to do with medicine or even with the history of medicine. In 1923, Torres, Marques da Cunha, Lessa, Villela, and Fonseca came to Chagas’s defense. In A Folha Médica they published a series of articles offering a positive assessment of research on the new disease and pointing out the incompetence of Chagas’s detractors. Chagas knew full well that the attack on him was a work of treachery executed by the wretched Peixoto. He might well have subscribed to the conclusion of an article that appeared in the newspaper O Brasil on November 18, 1923: “Jealousy is the sole reason for this debate, which in the end will contribute nothing to the progress of Brazilian science.”

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The polemic, some argue, was not without consequences. Historians contend that most physicians turned away from the study of Chagas disease. A decade-long “oblivion” ensued, they tell us, only to end abruptly when American trypanosomiasis was supposedly “rehabilitated.” The “revival,” moreover, was allegedly the work of one man: “Mazza traveled throughout Argentina, raised the issue, aroused the interest of his colleagues, looked for suspected cases in the appropriate places, and completed a scientific mission that may be counted among the most brilliant ever conducted in South America.”1 To explain what Mazza allegedly achieved, historians generally point to the rediscovery of the most salient sign of the disease, facial swelling. “Thanks to the work of Mazza and his collaborators, other characteristics of the disease previously noted by Chagas again came to to the fore and took on an importance that had not been suspected initially.”2 They also point to improvements in diagnostic technique. More recently, Perleth has explained why so few cases were recorded before 1935. For one thing, methods were rudimentary: One could either observe the parasite in the blood or inoculate animals with blood from suspected patients. For another, the absence of laboratories in rural areas is supposed to have made it difficult to identify new patients. Finally, the small number of confirmed cases made comparative study of different diagnostic methods difficult. “This meant that data regarding the sensitivity and specificity of these methods remained scarce. Had more sophisticated diagnostic techniques been implemented earlier to screen the population in regions where infected triatomine vectors were found, the extent of the endemic nature of Chagas’ disease as well as the chronic course of the infection might have been recognized sooner.”3 103

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Presumably, then, it was by refining the methods of diagnosis that the Argentine school revived the study of American trypanosomiasis. The Argentines, we are asked to believe, completed the work of Chagas by confirming his brilliant insights. What the work of Mazza and his disciples ostensibly proved was that Chagas disease was indeed a widespread endemic. We must not be misled by these historical reconstructions. Consider, for a moment, the methodological assumptions that these historians make. From 1909 to 1935, only a few dozen cases of the disease had been identified; after 1935, hundreds of cases emerged. What the historians argue is that this quantitative change in the “revival” period came about because a reliable diagnostic method was at last applied on a large scale. Presumably, then, the small number of cases recorded previously was due to the inadequacy of earlier methods. But this explanation cannot withstand scrutiny. The Argentines used the same methods as earlier practitioners: Most of the cases identified after 1935 were confirmed by examination of the blood or by the “thick drop” method. Furthermore, when Perleth says that “Mazza rediscovered the disease in Argentina,” he implies that the disease previously discovered by Chagas was the same as the one now rediscovered in Argentina. What he fails to see is that after 1935, this ceased to be true. Before that date, Chagas disease was understood to be a parasitic thyroiditis with cardiac and nervous complications associated with goiter. What happened in 1935 was not the rediscovery of an earlier disease but the first diagnosis of American trypanosomiasis. And the reason why a great many cases could now be identified was that the medical understanding of the disease had undergone a complete revision. It is hard to see how American trypanosomiasis could have been diagnosed before 1935 because the very idea of the disease precluded its discovery. The epidemiological character of the malady changed as new light was shed on the nature of this parasitosis. In order to grasp this point, we must focus not on the work of Mazza but rather on that of Romaña. To be sure, “Romaña’s sign” became a key feature in identifying the disease. But that is not the main point: It became possible to identify American trypanosomiasis clinically because Romaña had raised and resolved the difficult problem of identifying the pure form of the malady. Historians of medicine have for too long been fixated on a simple fact: the sudden increase in the number of cases diagnosed. This shortsighted approach has prevented them from seeing how medical perception

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was transformed in this period. Thanks to Romaña’s discovery, doctors finally knew what they were looking for. This chapter will examine the final process that led to recognition of the pure form of Chagas disease. It is easy to get lost in the detail of events. For a little more than a decade (from 1923, the date of Chagas’s final brief in his own behalf, to 1935, the year in which Romaña described the oculopalpebral syndrome), Chagas’s medical system was an important focal point of research. Because historians have generally failed to pay attention to the critiques of Brumpt, Kraus, Maggio, and Rosenbusch, they have also overlooked the fact that, in Manguinhos, a new generation of researchers now followed in their footsteps. The early critics suspected that Chagas had made a series of mistakes. The work of Dias, Penna de Azevedo, and Lobo Leite showed that they were right. But before American trypanosomiasis could rise from the ashes of previous misconceptions, an epistemological transformation was necessary, along with the constitution of a new syndrome: the oculo-palpebral complex. Romaña’s description of this syndrome was not the result of sudden curiosity about the acute form of Chagas disease but rather a consequence of his turn toward clinical medicine. In other words, the focus of Romaña’s research was fundamentally different from that of his contemporaries. The young Argentine doctor ignored the mode of transmission of the disease, turned his back on experimental medicine, and ceased to worry about overlapping diseases. The mere fact of working in a region free of goiter allowed him to make clinical examinations of patients who came to see him of their own accord. Then and only then did the observation of unilateral palpebral edema suggest a contaminative pathway for the disease. Until then, the only sign of Chagas disease had been identification of the parasite; Romaña discovered its pathognomonic sign. The new situation was the key: It allowed Romaña to observe the acute phase of the disease, the period of invasion. The formation of the concept of American trypanosomiasis is a chapter in the history of clinical medicine, not of diagnostic technique. Curiously, Mazza showed that it was Chagas who had first discovered the ocular sign. That is why his account was so well received by most Brazilian historians: He emphasized the endless fertility of Chagas’s work. But make no mistake: That was not Mazza’s purpose. In crediting Chagas with the discovery of palpebral edema, Mazza not only

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denied Romaña the credit he deserved but also claimed credit himself for spreading word of the sign that marked the revival of Chagasian studies. The ultimate conflict therefore pitted Mazza and his disciples against Dias and Evandro Chagas, who had immediately grasped the significance and implications of Romaña’s clinical investigations.

The Threefold Error Throughout the third decade, Chagas’s collaborators explored avenues of research that he had pioneered. These were three in number: the modes of transmission of the disease, its clinical manifestations, and its epidemiology. The researchers also tried to resolve issues that had been raised in the previous decade’s debates. The first problem was to figure out how the parasite penetrated its host and explain its life cycle. Chagas and his supporters had argued that the infectious stage culminates in the salivary glands of the insect vector. Brumpt and his followers argued that the life cycle was completed in the insect’s gut. The second problem had to do with the interpretation of the signs of hypothyroidism associated with the disease. Some, including Chagas, continued to associate myxedema and thyroid hypertrophy with a parasiteinduced disorder of the thyroid gland. Others, including Kraus, were dubious about the existence of thyroid symptoms and lesions in Chagas disease. The third problem involved the parasitic etiology of goiter and cretinism. Chagas’s disciples asserted a causal relation between the parasite and signs of hypothyroidism. The proponents of a hereditary-infectious etiology of goiter and cretinism argued that their clinical presentation had nothing to do with Chagas disease. New empirical data did not emerge until the 1930s, when younger Brazilian doctors sought to liberate themselves from the authority of Chagas. First, Dias studied the life cycle of Trypanosoma cruzi and concluded that the contaminative pathway was correct. Then Penna de Azevedo investigated the histopathology of samples taken from patients whose blood had been found to contain parasites. He found thyroid lesions characteristic of classic forms of goiter and cretinism. Finally, Lobo Leite conducted new

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epidemiological studies in Minas Gerais. After identifying a pure form of goiter, he was able to show that it was consistent with much of the symptomatology of the acute and chronic forms of Chagas disease as described by Chagas. Taken together, this work showed that Brumpt’s theory was correct; Kraus’s suspicions were confirmed by histopathological and epidemiological studies. Instead of the acute and chronic forms of parasitic thyroiditis described by Chagas, it was finally clear that he had confused two simultaneous afflictions: a form of parasitosis and the only form of goiter. Among the possible modes of transmission of the disease, Chagas had considered the possibility of an intrauterine pathway. In favor of this hypothesis were, first, the detection of signs of hypothyroidism in numerous newborn children of affected parents and, second, the detection of parasites in the ovaries, testicles, and seminal ducts. In 1921, Nattan-Larrier published his results concerning experimental infections of guinea pigs. It proved possible to infect offspring by injecting parasites into the uteruses of fertilized females. The trypanosome then appeared in the blood of the offspring: “We concede that Chagas disease and Debab [a North African name for a bovine trypanosomiasis] are the only trypanosomiases whose pathogenic agents can cross the placenta to contaminate the fetus.”4 Although Bruni’s results were negative, the congenital pathway was confirmed by experiments carried out by Villela and Souza Campos. Villela observed cases of acute encephalitis in contaminated puppies, and Souza Campos found trypanosomes and Leishmanian forms in their bodies. In short order, Brumpt, Neiva, Mayer, and Rocha-Lima showed that metacyclic trypanosomes could penetrate via the mucosa of the mouth and vagina. This led to the idea of looking to see whether Chagas disease, like dourine, could be sexually transmitted. Once again, it was Nattan-Larrier who performed a series of experimental infections. He showed that the trypanosome could easily penetrate the mucosa of the vulva and vagina, recalled Vianna’s histopathological findings, and hypothesized that genital contagion could be effected at least in laboratory animals. In 1913, the French doctor also found the parasite in breast milk. In 1916, Lanfranchi showed that mammalian trypanosomes can pass from mother to child by way of breast milk. A series of experimental infections proved that the disease could be passed on to offspring via this new pathway. The milk of female guinea pigs inoculated during the first months of

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pregnancy revealed the presence of trypanosomes, leading to the hypothesis that newborns can be contaminated by breast feeding. But these modes of transmission were believed to be exceptional. The most heated controversy concerned the life cycle of the parasite in the vector and its mode of penetration of the vertebrate. Schaudinn’s school was pitted against Brumpt’s. Chagas and his supporters reaffirmed the existence of a sexual cycle giving rise to infective forms. In 1926, Chagas was still defending his hypothesis that the parasites found in the body of the insect were the products of fertilization. In that same year, Muniz seemed to confirm this view: “It may be that the shape we observed represents the beginning of fertilization, and the aspect of the nucleus of the slender form is a prior chromatic reduction. Subsequent research may shed light on this point. All signs point to the possible existence of fertilization phenomena in certain cultures of Trypanosoma cruzi.”5 But Gaillard immediately warned him against placing too much trust in appearances, especially when observing old cultures. A second point of disagreement followed from the first: If the trypanosomal forms were the products of fertilization, they were found in the salivary glands, and transmission took place by inoculation. In the line of work done by Magarinos Torres, the Argentines Mülhens, Dios, Petrocchi, and Zuccarini obtained positive results by allowing guinea pigs to be bitten while obstructing the contaminative pathway. But Gaminara, Taliaferro, Niño, Kofoid, and Donat obtained negative results using the same experimental protocol. They observed infections in experimental animals after depositing excrement on the mucous membranes of the mouth and eye. To resolve these differences, Dias conducted a series of experiments on the transmission of the parasite from the insect to the vertebrate host. He infected laboratory animals by way of bites as well as by deposition of infected excrement on mucous membranes. Several guinea pigs were bitten by triatomids with negative results. Evandro Chagas then went to work on human subjects and showed that it was impossible to transmit the disease to a volunteer via the bites of infected insects. Verterbrates could be infected only if infected excrement contacted the mucous membranes or a lesion due to scratching. But how then could one explain the positive results obtained via bites? Perhaps the proboscis of the insect had been infected accidentally after an injury or via coprophagy, or perhaps the content of the insect’s gut had been regurgitated during the act of sucking.

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The clinical anatomy of the various phases of the disease had never been carried to such lengths, but these examinations involved only laboratory animals. In 1912, Mayer and Rocha-Lima had found the trypanosome in subcutaneous, connective, and adipose tissue. Villela, Dias, and Souza Campos examined pathological changes at the point of inoculation of the parasites. They described inflammations, edemas, and ulcerations reminiscent of the lesions observed in the cutaneous form of Leishmaniasis. The rapid multiplication of the parasite revealed its affinity for the reticuloendothelial system. Chagas and Villela soon described the cardiac and nervous forms of American trypanosomiasis. Souza Campos, Torres, and Evandro Chagas studied the clinical anatomy of the chronic forms. New methods were employed: Radiological examination of humans revealed cardiac hypertrophy, and the electrocardiograph made it possible to record changes in cardiac rhythm. Evandro Chagas was therefore able to describe total tachycardia, total brachycardia, total arrhythmia, nodal rhythm, gallop rhythm, idioventricular rhythm, and various types of blockage: total, partial, sino-auricular, intra-auricular, and intraventricular. In the nervous form, pathological anatomy revealed inflammatory foci in the brains and spinal cords of experimental animals. Lesions of the central nervous system were related to signs of functional impairment. Finally, clinical and histopathological examinations were extended to a wider population. New syndromes previously suspected by Chagas were described. As early as 1916, Chagas thought that evidence of dysphagia, known colloquially as “mal de engasgo,” might be linked to the action of the parasite. Villela ascribed a series of gastrointestinal symptoms to effects of the parasite on the digestive system. Evandro Chagas was one of the few physicians to study the disease through human experimentation on cancer patients, but with the exception of myocardial lesions, his work added nothing new to the clinical anatomy of the disease. This was because the symptoms of trypanosomiasis were masked by the cancerous cachexia. Finally, Souza Campos and Toledo Artigas conducted histopathological examinations of relatively unstudied organs: the lymph nodes, kidneys, lungs, and thymus. Oddly enough, the study of symptoms linked to lesions of the thyroid lagged behind. This was a crucial issue, however, because of its bearing on the semiology of the acute and chronic forms of the disease. Chagas had always insisted that myxedema and thyroid hypertrophy were expressions of

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an endocrine disorder caused by the parasite. On this point, doctors continued to rely on a small number of autopsies. Some of these confirmed the findings of Vianna and others, while others supported the results of Mayer and Rocha-Lima. In 1923, the American pathologist Crowell described the parasites found in the glands and the characteristic lesions of parasitic thyroiditis. In experimental animals he noted the enlargement of the cells of the thyroid and the presence of parasites in the vessels. In 1932, de Coursey performed an autopsy that contradicted Crowell’s findings. He found Leishmanian forms in the heart but nothing in the thyroid: “The thyroid was firm, symmetrical, and normal in size and color. It showed no microscopic lesions.”6 In the same period, Kofoid and Donat found lesions in the gland but hesitated to blame them on the parasite. Did the symptoms of hypothyroidism belong to the clinical picture of Chagas disease, or were they associated with a coincident malady? In 1933, Penna de Azevedo took a fresh look at the five acute cases identified by Chagas, in whose blood the parasite had been found. He was unable to find lesions indicative of parasitic thyroiditis: no interstitial inflammatory process, no cellular infiltration, and no parasitic cysts. On the other hand, he observed lesions typical of goiter as observed in Europe: “In all cases we found diffuse hyperplasia of the thyroid gland, with little variation in the type of hyperplasia from case to case. . . . The diffuse parenchymatous goiter of the newborn was of the histological type prevalent in acute forms of Chagas disease. This is also the anatomical type of endemic goiter commonly found in children in Europe.”7 Subsequently, Penna de Azevedo examined a series of thyroid glands from individuals exhibiting the chronic forms of Chagas disease and found no lesions of parasitic thyroiditis. He did, however, find histopathological changes comparable to those found in goiter in parts of Europe and North America where goiter was endemic. Epidemiological studies revealed many new vectors and reservoirs of the parasite but few cases of the disease. Most diagnoses resulted from largescale hematological examinations. Although the symptomatology coincided with Chagas’s in some cases and differed in others, the overall clinical picture of parasitic thyroiditis went unquestioned. Everyone invoked the same nosological entity, the one that Chagas had defined years earlier. In Peru, where Escomel had already found one case, Noguchi described another in 1924 after examining the blood of patients for the yellow fever parasite. In Argentina in 1925, Mülhens, Dios, Petrocchi, and Zuccarini

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found two patients. They were working in an area in which malaria was endemic. The first patient presented with a mixed infection, not really suitable for clinical study, while the second presented with slight hypertrophy of the thyroid. In the same year, Dios, Zuccarini, and Oyarzabal described a third patient: The thyroid isthmus was perceptible on palpation. They failed to observe the symptoms described by Chagas but assumed that they must have appeared at an earlier stage. Borzone and Coda found a fourth patient: A child presented with skin pigmentation reminiscent of melanoderma. In 1925, Mazza described Chagas disease in a woman of twentyseven: “Our patient, who may be the first adult observed in this country, presented at the time of the examination with quite visible thyroid hypertrophy, including the isthmus and both lobes, slight exophthalmia, and tachycardia, . . . splenomegaly and hepatomegaly.”8 In 1927, Niño found a sixth patient: “Hypertrophy of the thyroid gland . . . on palpation one does not feel the liver or adenopathy.”9 In the same year, Mazza described a child of five with a slight hypertrophy of the thyroid and edema, but he found no parasite in the blood. In 1929, Geoghegan found three asymptomatic patients with parasites in their blood. In the same year, in Ecuador, Martinetti described two patients, both with facial edema and one with an enlarged thyroid. In 1931, in Panama, five asymptomatic subjects were identified, three by Miller and two by Clark and Dunn. These were in the context of blood examinations on populations affected by malaria. In Guatemala in 1933, Reichnow examined the blood of a hundred children in a malarial region and detected the parasite in three of them. The diagnosis of a small number of patients by identification of the parasite in the blood left the problem of the parasitic etiology of goiter untouched. The only new element, which supported Chagas’s theory, was introduced by Lacorte. In Lassance in 1927, he performed the complement fixation test on the blood of a hundred patients with goiter. Eighty showed a positive reaction: “Our judgment is that this fact strongly supports the hypothesis formulated by the discoverer of the disease, according to which endemic goiter in this region is caused by Trypanosoma cruzi.”10 In Argentina, however, Kraus still contested the parasitic theory of goiter. Munk, Mülhens, Dios, Petrocchi, and Zuccarini shared his view: The absence of the parasite in the blood of goiter patients led them to reject the causal relationship established by Chagas. In Brazil, Baeta Vianna was one of the few doctors to challenge the parasitic theory of goiter. In a village

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near Belo Horizonte, he found a population affected by goiter without any sign of infected bugs: “The absence of the transmitter in Ouro Branco rules out, at least provisionally, Chaves’s hypothesis that parasitic thyroiditis is the cause of endemic goiter, whose existence here has been confirmed.”11 But Baeta Vianna’s position was not firm: He revived Chaves’s hypothesis that parasitic thyroiditis might be the expression of two coincident diseases that mutually reinforce each other. The question remained open. Was goiter part of Chagas disease? Or were the signs of hypothyroidism indicative of a different morbid entity? In order to rule out the parasitic theory of goiter in Minas Gerais, it sufficed to diagnose goiter in the region, for which it was of course necessary to find a site without infected insects. Lobo Leite was after something more, however: certainty beyond a reasonable doubt. He showed that animals and bedbugs were parasite-free. The clinical account was also taken into consideration. The characteristic signs of hypothyroidism were the following: thyroid hypertrophy, myxedema, cretinism, infantilism, deafness, and muteness. All of these signs were indicative of goiter. A negative diagnosis would therefore be conclusive: “We inoculated nearly 200 guinea pigs with the blood of individuals suffering from goiter, from Lobo Leite, Murtinho, and Ouro Blanco. After observation for a period of four to five months, all the animals were free of trypanosomes. . . . We believe that endemic goiter in this region is no different from endemic goiter in other countries and cannot be attributed to trypanosomiasis.”12 Lobo Leite had identified the pure form of endemic goiter in Minas Gerais. The pure forms of Chagas disease had not been identified in either the acute or chronic phase, however. To be sure, the chronic form was suspected in patients exhibiting certain cardiac syndromes and nervous disorders, but these signs were always associated with goiter. Villela deplored the gaps in the semiology: “The clinical studies were not done carefully. Nearly all investigators were satisfied with laboratory verifications. It would be very instructive to know the clinical features of Chagas disease.”13 The gaps in the semiology were not the result of negligence or inattention. Villela could not do more than his contemporaries and had to make do with laboratory verifications as well. The situation was paradoxical. It was impossible to isolate the cardiac and nervous forms of the disease because they were combined with goiter. For that very reason, goiter in insect-infested areas was the surest sign of the existence of chronic forms of

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Chagas disease. So doctors had no choice but to rely on the diagnosis: “The difficulty of deciding exactly what symptoms belong to Chagas disease as opposed to some simultaneous malady forced us to rely on laboratory methods.”14 Villela also performed the complement fixation text on the blood of nearly two hundred patients with goiter. There were fifty-three positive reactions, confirmed by inoculating guinea pigs with blood from these patients. As for the acute form of the disease, the path forward was similarly blocked. Dias’s work in Lassance showed that semiology had reached a dead end. He blindly examined the blood of the entire population because there was no sign he could use to narrow his investigation. April 1933: “We did not find the trypanosome in blood freshly drawn from sixty children living in infested homes, regardless of whether or not they were suspected of having the disease.”15 April 1934: “In attempting an etiological diagnosis of the disease in question . . . , we tested all the inhabitants of the region indiscriminately wherever it was possible to do so.”16 Another failure: Tests on fresh blood or thick smears from a hundred children proved negative. At most one acute case might have been identified by the presence of the parasite in the blood. When Dias went to Lassance, he was hardly better prepared than Chagas had been in 1909. Twenty-five years after Chagas’s discovery, Brazilian researchers were back at square one. What are we to make of this “snapshot” of Brazilian medical research in the period 1930–1934? First, Dias’s experimental infections had removed all doubt about the contaminative pathway. Hoare’s experiments showed that Trypanosoma cruzi belonged to the group of parasites that complete their life cycle in the “posterior station,” as opposed to the “anterior station.” Subsequent histopathological examinations by Penna de Azevedo proved that Chagas, in describing the acute form, had confused two superimposed diseases: a parasitosis and the classic forms of hypothyroidism. Finally, Lobo Leite’s epidemiological studies showed that the semiology of goiter and cretinism had to be eliminated from the description of Chagas disease. But this threefold advance in medical knowledge soon reached its limits. A series of problems remained unresolved. The experimental infections pointed to a contaminative pathway but did not reveal the natural transmission mechanism. The histopathological research identified the characteristic lesions of goiter, but the correct clinical description of Chagas disease

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remained unknown. Epidemiological research showed that goiter existed without American trypanosomiasis but failed to demonstrate the converse. These three impasses were related to the configuration of the medical field at this point in time: The objective pattern that emerged was intimately related to the conceptual instruments and techniques employed. Experimental infections performed on laboratory animals led to study of the mode of transmission of the disease and the clinical anatomy of the period of invasion following inoculation of the parasite. A number of consequences flowed from this. Focusing on the contaminative pathway, a problem of biology, led researchers to overlook specific lesions. Conversely, when researchers focused on lesions at the point of inoculation, they were looking at lesions associated with an experimental disease. This laboratory work left untouched the question of symptoms associated with the initial phase of the disease in nature. Similarly, histopathological examination of the thyroid led to the idea that the facial symptoms were the expression of a thyroid disorder. Finally, in the realm of epidemiology, the absence of any sign of the acute form meant that the disease had to be diagnosed by other means, and the chronic forms were always combined with goiter. In such a setting, it was impossible to arrive at a proper clinical description of Chagas disease. The proper vantage point for perceiving the symptoms associated with natural contamination in the acute phase was out of reach. Thus we can imagine how much effort it took to perceive something as apparently trivial as palpebral edema. Before Romaña could recognize this sign, he had to solve a problem of medical geography, adopt a clinical point of view, and establish a conceptual framework that would enable him to suspect its existence.

Romaña’s Sign In 1934, Reichnow summed up the state of research on Chagas disease in Latin America. In addition to the cases identified in Brazil, some thirty other cases had been found in other countries. Long after Chagas’s discovery, the situation remained problematic: Infected insects were widely distributed, but only a few dozen cases of Chagas disease had been identified. This disparity lent credence to those who doubted that the disease was widespread. But in the following year Romaña published a much noticed

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article: “Concerning a Reliable Initial Symptom for the Diagnosis of the Acute Form of Chagas Disease.” As this sign became widely known, the number of confirmed cases soon increased sharply. Within a relatively short period of time, American trypanosomiasis achieved an unprecedented status. No longer was it a rare malady, not to say a mere pathological curiosity. Now it was an endemic disease present in every country in South America. In 1936 Dias wrote: “During the last few years, remarkable progress has been made in the study of Chagas disease. . . . Today it is recognized as a true continental scourge.” He connected this transformation with Romaña’s discovery: Facial edema was the clinical sign that made it possible to identify numerous cases of the disease. But he also expressed surprised that so obvious a sign had escaped the notice of so many Brazilian doctors: “Strangely, this sign went unnoticed by researchers in Brazil who studied the disease.” Dias mentioned several factors that might explain this blindness and the resulting stagnation of research. “First among the reasons for this delay is the multifarious and varied symptomatology of the known clinical forms, which makes differential diagnosis more difficult.” He also mentioned two additional factors. First, the complexity of the symptoms was such that most doctors had turned away from the clinic. Until recently, he argued, there had been little in the way of clinical work since the classic papers by Chagas. Second, the use of direct and indirect diagnostic techniques was not within everyone’s reach. As long as these techniques required specialized knowledge, the possibilities of diagnosis were necessarily limited. “For all these reasons, the existence of American trypanosomiasis went unnoticed for quite some time in areas where it has now been found.”17 It would be wrong, however, to accept these reasons as an adequate explanation of the lack of progress in Brazilian research on Chagas disease. Researchers had not been baffled by the complexity of the disease, but they had been fixated exclusively on the complex of chronic forms that Chagas had set before them. Dias’s explanation must be stood on its head: The complex symptomatology did not discourage study of the disease but aroused the curiosity of physicians. They liked using the latest techniques to make diagnoses in the laboratory, for example by studying the pathological anatomy of experimentally infected animals. Too little notice has been taken of the fact that the vogue for experimental medicine was a sign of failure: The impossibility of a clinical approach ruled out developing a semiology of

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the disease. Because Villela and Dias could not make a clinical diagnosis, they were forced to turn to parasitological diagnosis. Once again, the order of factors must be reversed: It was not because diagnosis required specialist knowledge that doctors failed to identify Chagas disease, but rather because the disease could be identified only by parasitological techniques. Dias failed to grasp the impasse in which he found himself: Finding a parasite in experimental animals could at best prove the existence of some form of parasitosis. In order to diagnose large numbers of cases of American trypanosomiasis, one first had to forge a concept of the disease. Dias does not try to identify epistemological obstacles in his historical account. Its function is one of retrospective justification: If Romaña provided a clinical account of the acute form of the disease and rediscovered the contaminative pathway, the most recent research in Manguinhos had been headed in the same direction. Dias thus called attention to the relevance of his own work: He pointed to the experimental infections that had demonstrated the pertinence of the contaminative pathway and to his description of lesions in the reticuloendothelial system at the point of inoculation. But neither his research nor that of Penna de Azevedo or Lobo Leite had done much to lay the groundwork for Romaña’s discovery. To be sure, Romaña had spent a good deal of time at the Cruz Institute in 1934. Oddly enough, it was the young visitor who instructed the teachers who were supposed to complete his medical education. Two events demonstrate this point directly. In April 1934, Dias had identified one positive case by applying xenodiagnosis to some forty subjects. When Dias examined this patient clinically, Romaña was with him: “Upon returning in August, we examined this child along with Dr. C. Romaña and found a slight enlargement of the spleen and liver, tachycardia, and a notable increase in the volume of the heart.”18 This was no accident: It was also in August 1934 that Chagas performed the first experimental contamination of cancer patients via the conjunctive pathway. He noted the local inflammation pointed out by Romaña, the pathognomonic sign of the disease. The chronology speaks volumes. By the time Romaña arrived at the Cruz Institute, the die had already been cast. Consider the lecture he gave in August 1934 at the National Academy of Medicine in Rio de Janeiro, entitled “New Research on Chagas Disease in the Argentine Republic.”

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One imagines that Carlos Chagas listened to Romaña with satisfaction mixed with regret. Satisfaction, because he could for the first time be certain that his struggle had not been in vain. Regret, because the description of six acute cases revived two avenues of research that he had previously ruled out. One of these he might have explored had he not accepted the advice of his teachers Couto, Pereira, and Austregesilo, which led him to identify the facial swelling he saw with myxedema. The other was one that he had stubbornly resisted because he was under the influence of German protozoology, which led him to favor sexual dimorphism and the inoculative pathway. In his final years, Chagas was certainly aware of having missed a key point: palpebral edema associated with an infection of the conjunctiva. Broadly speaking, Romaña had reverted to the method of symptomatic analogy, using Brumpt’s framework to interpret trypanosomiases as the result of contamination rather than inoculation. In 1912, Laveran, in collaboration with Mesnil, had published a second edition of Trypanosomes and Trypanosomiases in which he summed up what was known about the clinical aspect of trypanosomiases. What he reported had already been known for several years: the importance of facial edema and adenopathy in the early stages of the disease. In the same year, Brumpt published his work on the life cycle of the parasite, “Penetration of Schizotrypanum cruzi via the Healthy Mucous Membrane of the Eye.” Romaña believed that he was merely rediscovering the common clinical description of the contaminative pathway in trypanosomiasis. A period of latency separated Laveran’s text and Brumpt’s discovery from their use by Romaña: This was the period of twenty years during which Chagas’s medical system reigned supreme. That was the obstacle, not the series of reasons given by Dias. The inoculative pathway had been linked to a host of organic disorders. That is why the facial symptom was associated with a lesion of the thyroid gland. For more than twenty years, Chagas and his school prevented Latin American medicine from understanding what the semiology of trypanosomiases and Brumpt had to teach. The conflict was not between Brazilian medicine at the end of its tether and a young Argentine doctor but rather between two distinct models of the disease. As long as the pathogenic process of Chagas disease was modeled on that of endocrine disorders, the facial swelling was seen as an expression of hypothyroidism. Once Romaña formulated the idea that Chagas disease was a

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parasitosis similar to other forms of trypanosomiasis, the unilateral palpebral edema became the signifier of the contaminative pathway. What enabled Romaña to transform Chagas disease into a parasitosis was the consistency of his professional experience. In 1931, at the age of 32, he earned his doctorate in medicine from the medical school of the University of the Littoral in Rosario. Before taking his diploma, however, he had already been practicing for ten years at the Home Hospital of the company La Forestal Argentina in the forests of northern Santa Fe province. In 1934, he joined the Regional Pathology Study Mission at the University of Buenos Aires as an auxiliary physician. This institution, which had its headquarters in Jujuy, was a creation of Mazza, who in 1928 had proposed to work on the social and medical problems of rural areas. Romaña took Mazza’s courses, and Mazza had him study a thesis by Niño titled “Contributions to the Study of Chagas Disease” (1929). This offered him a good overview of what was known about the malady, and he was soon thoroughly familiar with all the issues raised by this strange pathology. Romaña had an opportunity to observe the trypanosome, the infected vectors, and the reservoir animals in the field. In 1931, he co-authored a first article with Mazza and Schürmann titled “New Observations on the Spontaneous Infection of Local Armadillos by Trypanosoma cruzi.” In 1932, in collaboration with Schürmann, he wrote “Spontaneous and Experimental Infection of the Armadillo of Chaco Santafesino by Trypanosoma cruzi,” and, with Mazza, “Spontaneous Infection of Marsupials of Chaco Santafesino by Trypanosoma cruzi.” But the crucial factor was Romaña’s practice of medicine in a rural area: There all the conditions necessary to perceive the pure forms of Chagas disease were satisfied. First, the recognition of the disease required that a geographical region in which the disease existed coincide with a hospital catchment area. The geographical region had to be a select natural environment in which the disease existed without other pathologies that might mask, disturb, or complicate it (such as goiter and malaria). The hospital catchment area was a place where patients could come together: It was both an institutional and a strategic environment, in which the disease could unfold from the moment of infection to the chronic phase. Romaña did not discover the pathognomonic sign of the disease by scouting out patients but rather by practicing medicine in a hospital located in a favorable area. “It was not difficult to identify the early stage of acute

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infection among the patients who came regularly to the outpatient clinic of the Villa Guillermina hospital. The number of acute cases seen thus far is six. . . . They were found among the dispensary patients without any systematic effort to sort them out.”19 Romaña’s brilliant theoretical stroke was to look for the sign of the disease in a different place. Parasitic thyroiditis, encompassing manifestations of hypothyroidism, was understood as an endocrine disorder, but an exceptional one owing to its causal agent. Romaña turned this approach around: Among diseases caused by parasites, it was the entity invented by Chagas that stood out as an exception. He therefore tackled the nosological singularity by looking for a symptomatology that would correspond to a parasitosis. In February 1932, when Romaña identified the first acute case, he had already formulated a clear statement of the issue: Chagas disease was either an endocrine disorder or it was a parasitosis. The absence of any sign of hypothyroidism would then establish that the pathological manifestations of the disease were those of American trypanosomiasis. It was not possible to see the incompatibility between endocrine disorder and parasitosis until a clinical description adequate to distinguishing between the two had been constituted, however. That description depended in turn on satisfying a certain set of conditions. It was because Romaña made sure that all those conditions were satisfied that he was able to describe the pure form of Chagas disease. The region in which he worked had been carefully selected. The presence of infected insects, reservoirs of the parasite, and domestic animals constituted a series of signs: It followed that cases of the disease must exist. Furthermore, the danger of confusion with other diseases was eliminated: “These regions of the country, which are free of malaria and endemic goiter, are of great interest for the study of human infection by Trypanosoma cruzi, which has been the subject of much debate.”20 Because there was no malarial infection, symptoms such as enlarged liver and spleen could not be put down to the simultaneous effects of the malarial parasite. No endocrine disorder: An epidemiological study of children in the school of Villa Guillermina revealed no sign of goiter. Finally, no evidence of hypothyroidism was found in any of the clinical cases at any stage of the disease: “All our trypanosomiasis patients, whether acute (six cases studied) or chronic (two published and others still under study) presented with any

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symptom of thyroid hypertrophy, as can be seen in photographs taken for the purpose.”21 It would not be wrong to say that Romaña went back to the sources. He had only to consult any treatise on tropical medicine to learn that edema was a common symptom in a variety of parasitoses. In sleeping sickness and various animal trypanosomiases, doctors had described edemas without ever associating them with a thyroid disorder. Romaña lumped Chagas disease together with other trypanosomiases and therefore concluded that edema should be among its symptoms. He also shared Kraus’s doubts: The description of the acute form of Chagas disease, signaled by the presence of parasites in the blood, probably confused two diseases, a parasitosis and hypothyroidism. But in rediscovering the classic descriptions of edema along with Kraus’s doubts, he made one major modification. It was because Romaña saw a connection between these two things that he opened a new field of visibility. In order to identify the pure form of Chagas disease, he had to conceive of the disease in a way consistent with the clinical description of other trypanosomiases: an infiltration of the subcutaneous tissue could exist without signaling hypothyroidism. This idea enabled Romaña to get around the hypothesis that had governed all research on the disease for the previous twenty years. From the beginning he rejected the assumption that the most salient sign of the disease pointed to myxedema, an assumption shared not only by Chagas but also by Kraus and Penna de Azevedo. To resolve the symptomatology of Chagas disease, it was not enough to suspect the existence of two overlapping infections or even to prove this by histopathological examination. Indeed, the problem was not even recognized, since the myxedematous nature of the facial swelling was taken for granted. The only question was what morbid entity was to be associated with the myxedema: parasitic thyroiditis, as Chagas and his supporters believed, or hypothyroidism in combination with a parasitosis, as Kraus had suspected and Penna de Azevedo had shown. This led to the idea that no facial swelling should be associated with American trypanosomiasis. In order to discover the pure form of Chagas disease, Romaña had to avoid falling into the trap of “Same” and “Other,” which had ensnared all of his contemporaries. Swelling can be a sign of myxedema. But it can also signal inflammation, along with pain, redness, heat, and tumefaction.

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Clearly, Romaña had decided on a new approach, which differed in two ways from the old. He broke with Chagas by rejecting the idea that the swelling was an expression of myxedema. And he broke with Kraus and Azevedo by insisting that the swelling might be inflammatory in origin. A new structure of visibility then emerged: The unilateral palpebral edema could at last be seen. At first glance, one might think that Romaña shared Penna de Azevedo’s concern with breaking the link between American trypanosomiasis and goiter. But whereas the Brazilian confined himself to clarifying a problem of nosology, Romaña drew all the consequences of the hypothesis that the two diseases were unrelated. The relation between clinical examination and nosography therefore changed. Romaña’s major discovery, systematically recounted in his 1935 paper, was his description of the initial syndrome. He linked the unilateral palpebral edema to a local tissue disruption following a parasite invasion. The syndrome could be observed in a series of similarly infected patients. The edema stood out at once: “Onset is generally sudden, with swelling of the eyelids and conjunctiva of one eye.” There was no crackling when the swelling was touched and no imprint when depressed. It was elastic, painless, and violet to pink in color: “Injection and edema of the conjunctiva sometimes to the point of chemosis.” The ocular syndrome peaked on the tenth day. The edema extended to regions of the face near the affected eye and sometimes beyond. But it receded after several weeks: This was a key feature. A second key element was “the satellite lymph node reaction on the same side as the ocular inflammation, localized to the preauricular, parotidian, and submaxillary nodes. One node is usually larger than the others.” Romaña called this syndrome “unilateral schizotrypanosomian conjunctivitis”: “This important symptom, which was the only visible and obvious manifestation of the disease in our three most recent patients, was observed on various occasions during our professional practice in Chaco, though at the time we did not ascribe to it the importance that we do now thanks to knowledge of its true etiology.”22 This sign was usually accompanied by a series of other pathological signs: fever, tachycardia, and enlargement of the liver and spleen. Subsequently, other signs were identified, completing the original and fundamental account. In 1936, in “A New Case of Chagas Disease in Villa Ana (Santa Fe),” Romaña and Cereijo described the exophthalmia that sometimes accompanied

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the conjunctivitis. In 1937, in “Verification of the Schizotrypanosic Nature and Frequency of Dacrioadenitis in Chagas Disease,” Mazza and Benitez described dacryocystitis and dacryadenitis, indicated by inflammation of the lachrymal gland. Histological examination of a biopsy of the gland revealed Leishmanian forms in the inflammatory nodules. Once the edema was seen as the expression of a local inflammation, the conjunctiva emerged as the focal point of the cause of the irritation. Chagas’s perception of the causal mechanism of the disease was stood on its head: The most salient sign was no longer the indication of a thyroid disorder due to the parasite but the sign of a lesion at the point where trypanosomes in the excrement deposited by the bug entered the body of the host. In February 1932, Romaña, without even raising the question of the mode of transmission, identified the parasite’s point of penetration. Because the precocious edema was unilateral and associated with a lymphatic reaction on the same side, it was immediately designated a sign. The initial edema affected one eye: “A few days after the process began, we observed a prominent edema of the left eye accompanied by intense satellite adenopathy. This made such a powerful impression that it suggested the hypothesis that the conjunctiva was the portal by which the infection entered the body, . . . the site of penetration of the human organism by Schizotrypanum cruzi.”23 As Romaña observed additional cases, evidence in favor of the hypothesis became so solid that he subtitled his paper “Hipótesis sobre puerta de entrada conjuntival de la enfermedad” (Hypothesis concerning the conjunctival entry point of the disease). He now felt that he was in a position to dispel what still remained a paradox: the contrast between the wide diffusion of infected insects and the small number of recorded cases of the disease. We have already seen how Chagas resolved this problem: Given the frequency of insect bites and consequent inoculation of the parasite, the infection was general, he believed, and therefore went unnoticed. But if the edema was the sign of the infection, it was no longer general. The replacement of the inoculative pathway by the contaminative pathway led Romaña to link the bite of the insect to a risk of infection. Everyone in the population was certainly exposed to contact with contaminated excrement deposited by the insect while feeding. But the risk of contracting the disease was small because of the mode of contamination. The edema pointed to the mucosa of the eye as the natural entryway. Inaccessible during sleep, it was also a restrictive factor: “With

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the eyes closed during sleep, it is not easy for the excrement to reach the inner portions of the eye in victims attacked by the bugs; a number of things must occur simultaneously for this to happen. The difficulty that the infective forms of Schizotrypanum cruzi face in reaching the conjunctiva and penetrating the organism thus constitutes a natural limitation on wider diffusion of the disease.”24 In 1912, Brumpt had carried out experimental infections via the ocular membrane. In 1932, Dias confirmed this mode of transmission in laboratory animals. It would not be wrong to say that Romaña rediscovered the contaminative pathway discovered by Brumpt, but it would be quite insufficient as a description of his achievement. It was observation of the palpebral edema that led to the rediscovery of the contaminative pathway. Romaña thereby sidestepped the second (endocrine disorder) theme, which had dominated research for twenty years. This had interfered with perception of the natural mode of infection and therefore of the causal link between the contaminative pathway and the palpebral edema. One might even go so far as to say that variations on this theme multiplied the number of obstacles to a correct perception of the disease. Consider, for example, the intention of the experiment that involved depositing contaminated excrement on the ocular membrane: It was to resolve an issue pertaining to the biology of the parasite and to test its powers of penetration. Researchers still expected to find lesions when that pathway was transcutaneous, that is, inoculative. This was what was observed in sleeping sickness as well as in experimental infections in animals, and it formed the basis for the description of inflammations at the point of inoculation of Trypanosoma cruzi. Consequently, contamination via the mucosa went unnoticed. For Brumpt and his followers, man could be naturally albeit accidentally infected via the mucosa of the mouth. Hence the mode of contamination of Trypanosoma cruzi was understood in terms of that of Trypanosoma lewisi in rodents. For all these reasons, no one thought of questioning the myxedematous nature of the facial swelling. In 1936, Brumpt had yet to update the fifth edition of his Précis de parasitologie, even though it was billed as “entirely revised.” He persisted in describing what Romaña had just definitively ruled out: “Since these animals bite the lips and cheeks, they can soil the buccal mucosa of a sleeping victim with their excrement, and the entry point of the virus will go unnoticed.” As for the clinical forms, “All present with the various syndromes of thyroid insufficiency, hence the name

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parasitic thyroiditis.”25 Thus it was not enough to suspect the contaminative pathway or even to verify it experimentally as Dias had done to see the accompanying edema. Romaña did not rediscover the mode of transmission; he rather discovered, at the very beginning of his work, the solution to the problem of natural transmission. Until 1934, the life cycle of the parasite suggested a contaminative pathway. Romaña’s work showed that palpebral edema indicated a conjunctival pathway. The question of the etiology of the disease thus took on a new relation to the questions of the mode of transmission and initial lesions at the point of inoculation. With the ocular portal defining the typical syndrome, the conjunctiva could be seen as a moist environment favorable to the penetration of the parasite. After the ocular portal, a cutaneous pathway was soon discovered as well. Parasites could enter the organism by way of a lesion caused by scratching or by the bite of the insect itself. In 1936, Mazza, Romaña, Parma, and Zambra described a lesion similar to the one observed in sleeping sickness. Usually the process was localized to the cheeks, temples, eyelids, forehead, or hairy areas of the head. The “canker of inoculation” (Romaña) or “chagoma of inoculation” (Mazza) resembled a moderately severe boil or carbuncle. The key point is that Romaña’s discovery changed the way in which the epidemiology of the disease was approached. Patients were no longer identified by parasitological diagnosis. Instead, they were identified first by other signs, and only then was a parasitological diagnosis performed. This reversal clearly entailed a change in the nature of the object itself. As long as the indicator of Chagas disease was identification of the parasite, its prevalence was equated with the total number of patients. In nosological terms, doctors hesitated between parasitic thyroiditis and an indeterminate parasitosis masked by signs of hypothyroidism. But once the concept of American trypanosomiasis defined a parasitosis that could be identified by observing the oculo-palpebral syndrome, prevalence could be defined in terms of the number of cases of disease. The nosological ambiguities disappeared: Detection of the disease became routine. In principle, the malady could be recognized at a glance: “Some of the collaborators of the Mission (Dr. Romaña), and one of us (Mazza), were able to predict clinically the discovery of trypanosomes in the circulation of certain patients, especially children, presenting with a symptomatological

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picture that, once known, cannot be confused with any other process.”26 Of course the discovery of the pathognomonic sign of the disease did not mean that existing diagnostic methods were of no use. On the contrary, those methods remained essential for the diagnosis, but now they could be applied judiciously. The clinical diagnosis of Chagas disease encouraged rational use of diagnostic techniques. The discovery of Romaña’s sign marked a new era in the history of the disease. The number of cases now rose to hundreds and before long to thousands.

Mazza the Impostor The question of renaming American trypanosomiasis soon arose. In 1944, Talice wrote: “In strict justice it should be called Chagas-Mazza disease. Indeed, the work of Salvador Mazza in Argentina on this disease, especially in the last six years, has been so important, original, and fruitful, that any impartial observer must conclude that it is imperative to associate his name with that of the disease in question.”27 In 1953, on the occasion of the first National Conference on Chagas Disease, the minister of public health, Ramón Carillo, revived Talice’s proposal: “To make this homage concrete, I propose that this conference settle a question of nomenclature and recommend that the malady known as Chagas disease be renamed, at least in Argentina, Chagas-Mazza disease.”28 The proposal was favorably received, and the Argentine Society for Microbiology was charged with pressing the case at the next International Congress of Microbiology. In the meantime, however, the Brazilians did not sit still. In 1959, at the International Congress on Chagas Disease, the director of the Oswaldo Cruz Institute summed up the situation: “In Brazil, the name of the disease has been officially recognized since June 6, 1918, ratified by Article 1 of federal decree no. 13,055, which states among other things that the fight against ‘Chagas disease’ shall be among the top priorities of the rural public health service. This was confirmed by decree no. 13,139, with both decrees bearing the signatures of President W. Brazz and the minister of the Carlos Maximiliano government.”29 The effort was wasted. In 1971, Canal-Feijoo published an article titled “Social-Medical Aspects of Chagas Disease.” In 1974, Jörg, who was also a

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disciple of Mazza, published “Trypanosomiasis (Cruzi) in Humans, or ChagasMazza Disease.” In 1978, G. Basso, R. Basso, and Bibiloni wrote in the introduction to their work that “the immense efforts of the Mission for the Study of Argentine Regional Pathology, headquartered in Jujuy, completed the work of Chagas. That is why we believe that in strict justice, following the practice in other cases, American trypanosomiasis should henceforth be known as ‘Chagas-Mazza disease,’ as the title of our book indicates.”30 These repeated interventions on behalf of Mazza reveal a conviction widely shared in Argentine scientific circles: that the revival of the study of American trypanosomiasis in Latin American was due to Mazza. How did the idea of honoring Mazza come to pass? Mazza himself probably never asked for any such honor. Yet he did claim credit for the rediscovery that justified the association of his name with that of Chagas in the eyes of his compatriots. From 1935 on, Mazza repeatedly insisted that he was responsible for reviving the study of Chagas disease. The brilliant results obtained by his collaborators were due to his research and teaching at the Mission for the Study of Regional Pathology. Mazza soon gave his version of the crucial turning point: Chagas disease achieved the status of a continental scourge with the rediscovery of the pathognomonic sign of the disease. Why did he tell this lie? It all went back to the ninth meeting of the Argentine Society for Regional Pathology in Mendoza (1935), when Mazza was confronted with a version of events that he could not accept. Dias, who had been invited along with Evandro Chagas, started things off. After pointing out that Romaña had discovered the primary pathway by which the parasites entered the human host and identified unilateral conjunctivitis as an omnipresent syndrome, he took the initiative of proposing to name the syndrome after its discoverer: “A great many acute cases were recently confirmed in Argentina thanks to ‘Romaña’s sign,’ as justice requires us to name this very important syndrome, which has proved to be a reliable method of diagnosing acute cases of Chagas disease.”31 Sierra Iglesias, Mazza’s biographer, expresses regret that his hero never recognized Romaña’s contribution, a failing that he puts down to the pride of the master. No doubt this is correct. But what Sierra Iglesias does not say is that Mazza and his followers did everything they could to discredit Romaña. In a campaign of systematic slander, they attacked the professional ethics of the young Argentine physician. So vehement and so unrelenting

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were these attacks that in the end they poisoned medical research, and for no good reason: “We will show that the persistent attacks on this syndrome were totally unjustified and succeeded only in creating confusion that is still evident in the recent literature on the detection of this trypanosomiasis.”32 No sooner did the medical community embrace the idea that Romaña’s ocular syndrome allowed for rapid diagnosis of acute cases of Chagas disease than Mazza set about to put Romaña back in his place by rewriting history. Instead of crediting Romaña for the discovery, he credited Chagas. Mazza claimed that Chagas had described the characteristic lesions of unilateral conjunctivitis. This discovery, he argued, was enshrined in Chagas’s 1916 paper: “In his compilation of twenty-nine cases of the acute form of the trypanosomiasis observed in Lassance, Chagas carefully noted oculopalpebral phenomena, especially those occurring in one eye only.” Mazza supported his claim by pointing to a series of photographs of patients that Chagas had included in his paper: In most of the children, one sees a unilateral facial edema. By crediting Chagas with the discovery of the sign, Mazza was able to portray himself as the person who rediscovered it. For instance, he claimed to have used it in 1927 to identify a case of the disease in a five-year-old child named Eduarda Vilches: “The prominent edema of the eyelids and orbital region on the right side, along with the cervical lymph nodes on the same side, is what led us to the diagnosis of Chagas disease.”33 Mazza claimed already to have been teaching the ocular syndrome in courses and lectures that he gave in the interior of the country: in 1929 in Jujuy, in 1930 in Salta, and in 1931 in Tucamán and Reconquista in the province of Santa Fe. Photographs were offered as evidence, especially photographs of Eduarda Vilches. Mazza did not challenge the fact that Romaña had described acute cases but claimed that he did so under his, Mazza’s, supervision: Dr. Romaña, a young doctor who practiced in a subordinate position for ‘La Forestal’ and possessed some limited information about Chagas disease . . . benefited more than others from this instruction, as well as from our guidance and technical advice. . . . The voluminous correspondence in which Dr. Romaña later obliged us to engage reveals the insistence with which we urged him to look for Chagas disease in this region of Santa Fe, as well as our efforts to overcome his skepticism, which is evident in many of his letters. . . . That is how Dr. Romaña found his first acute case . . . , his second case . . . , and

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his third case. . . . . Up to that point, as we have seen, Dr. Romaña’s activity did not go beyond our suggestions, as we guided his efforts, not always without difficulty, and in which he did no more than his colleagues in the interior, all of whom were guided by and worked in the spirit of the MEPRA.34

We must take care not to be misled by Mazza’s historical reconstruction. Chagas did indeed recognize certain phenomena that would later be associated with unilateral palpebral edema, but he saw these as signs of myxedema, so we cannot conclude that he already recognized the syndrome. The photographs that Chagas took of patients always show the entire body. In order to see the oculo-palpebral syndrome in the photographs in the 1916 paper, the faces must first be cropped and enlarged. The crucial thing is not what Mazza saw in 1935 in enlargements made after the fact but what is in the text that accompanied the original photographs. The captions refer to parasitic thyroiditis. In order to prove that he had quickly grasped the importance of the ocular syndrome, Mazza also pointed to the case of Eduarda Vilches, who presented with “prominent edema of the eyelids and orbital region on the right side, along with the cervical lymph nodes on the same side.” This is misleading. A clinical account of this case was sent to Niño, who published it in 1929. At that time Mazza made no mention of the asymmetrical appearance of the face, because he did not see the connection between the palpebral edema and the adenopathy on the same side: “Slight hypertrophy of the thyroid gland. Edemas of the eyelids and extremities . . . despite the negative blood examination, this patient has all the features of the acute form of Chagas disease.”35 Clearly, Mazza did not at this point recognize Romaña’s sign in Eduarda Vilches. In 1935, Mazza again offered a post hoc enlargement of the little girl’s face: “The face in our photograph, reproduced by Niño on page 198 of his work, to which we add here a second photo, an enlargement of the face, shows significant edema of the eyelids and neighboring areas of the right eye.”36 In addition to the fraudulent use of retrospective diagnoses, Mazza was guilty of yet another lie. Mazza’s letters to Romaña give direct evidence that his disciple had embarked on an avenue of research so new that Mazza sought to insinuate his own name into Romaña’s publications. Consider the following series of cases in point. An infected dog (letter of June 26, 1930): “I urge you to present your observation of the infection of a dog in Salta

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very soon, or else we will do it.” Isabelino Martínez, the first acute case (letter of August 16, 1933): “Your work will be excellent for this new insight and not for what you borrow from Chagas or Niño, and to that end I will, if you wish, see to it that it does you honor.” Cervanda Canete, the second acute case (letter of November 14, 1933): “Your new case is splendid.” The three acute cases that Romaña identified in January 1934 (letter of May 26, 1934): “As for the other cases, if you have no objection (and feel free to make your own decision), I would like to join you in presenting them to the Congress. If you decide to present them alone, we will in any case publish them afterwards at the Mission.” Clearly, Mazza doctored the historical record in order to portray events in a certain way. By crediting Chagas with the discovery of the ocular syndrome, he portrayed himself as the person who took up the question at the point where Chagas had left it. There was no discontinuity in the research program, only a certain delay. From this it follows that Brazilian doctors, by overlooking the sign, were responsible for the delay in progress on Chagas disease. By giving himself credit for reviving and teaching about the sign, Mazza portrayed himself as the person who made progress once again possible. Romaña therefore could not claim credit for the slightest originality, and there was no justification for Dias’s proposal to name the sign after him. In 1939, Dias himself pointed out that Mazza’s version of history was anachronistic and showed that Chagas had not discovered the unilateral palpebral edema. To be sure, Chagas had indeed described facial swelling as a sign worthy of attention, since it aroused suspicion of infection at some point in the past. But Chagas and his collaborators saw the sign as a myxedematous infiltration due to an endocrine disorder: “These [swollen] faces cannot be compared with more or less localized palpebral edemas together with other signs such as unilateral schiztrypanosomic conjunctivitis, which Romaña interpreted as lesions at the point of entry.” Chagas had indeed pointed to a number of oculo-palpebral lesions. But these were mentioned in isolation and seen as exceptional lesions in the acute form of the disease. Furthermore, Chagas was never able to explain these ocular changes. He never described the triad of symptoms (palpebral edema, conjunctivitis, and adenopathy on the same side) that characterized Romaña’s ocular syndrome: “No legitimate doubt remains as to the priority in the discovery of the ‘eye sign,’ which some authors erroneously date from the time of Chagas’s first papers.”

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What is more, if Chagas had discovered the sign, the extent of the disease would have been recognized much earlier: “So many years would not have passed before recognition of the continental extent of American trypanosomiasis, which Chagas so often affirmed and others have so often denied.”37 In short, Dias was willing to credit Mazza with the role of teacher provided that the sign he taught was credited to Romaña. A glance at what MEPRA published in 1935 is enough to show that he was right. Take one example among those cited by Dias. In June 1935, at the invitation of the Medical Society of Paraná, Mazza gave three lectures. Caceres and Izaguirre remembered them: “Engraved in our memories were many illustrations of the particular symptomatology of the patients, and especially the sign of the eye, which had been established beyond a shadow of a doubt by the work of the Mission over which Mazza presided.”38 After Dias presented his critical version of this history, Mazza changed strategy and took the risk of contradicting himself. Unilateral palpebral edema, he now said, did not have the value ascribed to it: it was a crude sign without any particular importance. This about-face would be incomprehensible but for the new emphasis on a cutaneous entry point. Mazza retained the logic of his version of history but substituted another syndrome for Romaña’s sign. What Chagas had discovered was not the ocular sign but the cutaneous entry point. Mazza was thus able to take credit for discovering what he called the “hematogenic chagoma.” Contamination usually occurred by way of a lesion due to the bite of the insect. If Chagas disease began with a general infection, the pathological indications associated with the eye revealed an endogenous infection. For Mazza, conjunctivitis accompanied by dacryadenitis and exophthalmia indicated the propagation of a deep inflammation of the orbital tissue. The orbito-palpebral localization of the Leishmanian forms in the tissues indicated an internal infection. Compared with this, the contaminative pathway was less important than some claimed. There was no local exogenous infection by contamination of the ocular mucosa: “Clearly, Romaña’s sign is far from constituting an invariable syndrome of Chagas disease, which does not exist in the form described by Dr. Romaña and which therefore does not deserve the status of pathognomonic sign assigned to it by Dias.”39 Mazza pointed to the statistics: of the first five hundred cases to be identified, one hundred exhibited cutaneous entry points. It was time to forget about Romaña’s sign. A series

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of new names were proposed for the sole purpose of discrediting the name that Dias had proposed: “unilateral schizotrypanosomic ophthalmia” (Olle), “ophthalmo-lymphic initial complex (R. and G. Basso), “ophthalmo-glandular complex” (Zembra), “oculo-annexial symptoms” (Benitez), “primary Chagasic adenopathy” (Mazza and Jörg), “Chagasic dacryadenitis,” “unilateral erythrodermic palpebral edema with or without conjunctival reaction” (Mazza). In 1939, Brumpt tried to placate all sides by using the designation “Romaña-Chagas-Mazza sign.” But Romaña showed that the distinction between these various syndromes and “unilateral schizotrypanosomic conjunctivitis” was illusory. Mazza defined endogenous acute conjunctivitis by the following signs: palpebral edema, conjunctival hyperemia, chemosis, dacryadenitis, and exophthalmia. But this was just the definition of conjunctivitis. In fact, the ocular syndrome was characterized by a triad of signs: redness of the mucosa (hyperemia), tumefaction (chemosis), and abnormal secretion. Mazza had merely added dacryadenitis and exophthalmia to conjunctivitis, but these are inconstant phenomena due to the propagation of the morbid process toward deep tissue. “In considering what conjunctivitis is, it must not be forgotten that conjunctivitis cannot be reduced to the superficial epithelial sheath but includes the chorion, the glandules, and the underlying vessels, all tissues that participate actively in the pathogenic processes.”40 To establish the value of the ocular syndrome, Romaña performed an experimental demonstration. In 1939, he redid Brumpt’s experiment and produced the ocular entry syndrome in two monkeys by depositing infected excrement on the conjunctiva of one eye: “From its exact reproduction in the monkey, together with knowledge gleaned from the clinic and from parasitology and pathology, one can conclude that ‘unilateral schizotrypanosomic conjunctivitis’ in man must be interpreted as a syndrome, which, in all cases in which it appears, indicates the entry point of Chagas disease.”41 In the same year, Herr and Brumpt published an acute case of Chagas disease contracted accidentally by contact with a triatomid. They observed an infection identical to the spontaneous acute forms. Mazza’s attacks peaked with the publication of Zembra’s book, Chagas Disease: Its History (1944). In this work by one of Mazza’s obedient disciples we find all the unfair tactics already deployed by Mazza: anachronism, selective reading of the evidence, and falsehoods. Once again, history was wielded as a weapon in a settling of scores. There can be no doubt that Mazza played an

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important role in stimulating new work on regional pathologies. But it was a solitary figure without an institutional position who managed to put all the pieces together in such a way as to lift the epistemological obstacle that had blocked progress on the disease. There are few parallels to Romaña’s achievement in the history of medicine. And what is truly remarkable is that this work had such formidable real-world consequences: nothing less than the revelation of a continental plague.

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Conclusion

This book covers a rather short period of time: 1909–1935. In 1909, Chagas discovered Trypanosoma cruzi and began searching for the disease it caused. In the beginning, however, Chagas disease was interpreted in a way that today’s medical science would not recognize. Chagas formulated a medical system that enabled him to apprehend what he called parasitic thyroiditis. In order to arrive at this concept, he had to weave together strands of German protozoology, the clinical anatomy of endocrine diseases, and the infectious etiology of goiter. He quickly cobbled together an explanatory framework. It consisted of an etiology (the sexual life cycle of the parasite implied an inoculative pathway), an etiopathogeny (myxedema indicating an endocrine disorder), and an epidemiology (parasitic thyroiditis accounted for the goiter and cretinism observed in Minas Gerais). In 1935, an epistemological transformation made it possible to see Chagas disease in a new light, as a full-fledged member of the class of parasitic diseases. For more than twenty years, researchers had missed American trypanosomiasis. Sometimes the disease was masked by a concurrent malady, while at other times it was replaced by an experimental infection. Romaña changed all this in two ways, which allowed what had previously been imperceptible at last to be seen. To put it another way, the concept of American trypanosomiasis was elaborated only after medical researchers began to explore new terrain. This was true literally as well as figuratively: In Santa Fe (Argentina), unlike in Lassance (Brazil), no other malady coexisted with Chagas disease, and the hospital, as opposed to the laboratory, was a place where spontaneous natural infections could be observed. The replacement of experimental medicine by clinical medicine led to the development of a new etiopathogenic 133

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schema: At the point of contact with the conjunctiva, the parasite produces the oculo-palpebral syndrome. The true dimensions of Chagas disease could now be seen for the first time: It was a continental scourge. Historians like to say that the Argentine school “rehabilitated” Chagas disease. But was renunciation the price of rehabilitation? From the moment that Romaña’s discovery gave this parasitosis a new lease on life, the old parasitic thyroiditis was relegated to the status of a nosological curiosity and dismissed as “false.” The choice to end this essay in 1935 was intended to bestow on it the unity appropriate to a study of the formation of the concept of American trypanosomiasis. In this history, discovery proceeds in an order opposite to that observed in most other pathologies. Everything began in 1909 with the discovery of a pathogenic parasite, but it was not until 1935 that the disease corresponding to it was definitively identified. In the discovery of this parasitosis, time thus exhibits a certain “viscosity.” Our challenge in recounting this history was to make this viscosity intelligible. The usual linear history of medicine failed to do justice to the latency period between the discovery of the parasite and the formation of the concept of American trypanosomiasis. There was resistance to understanding the disease owing to the “thickness” of time. To see this, we had to explore the various conditions that had to be met before Chagas’s medical system began to dissolve, making room for uncertainty to creep back in. The critical period was the time between the discovery of the trypanosome and the discovery of the trypanosomiasis. Initiated by Brumpt, Kraus, and Kraus’s collaborators, it ended around 1934 or 1935: The life cycle that Brumpt had described was confirmed, as were Kraus’s suspicions. But it was still impossible to distinguish American trypanosomiasis from the hypothyroidism that Chagas had included as a sign of the acute form of the disease and often confounded with its chronic forms. Chagas disease could not be seen as a distinct entity because it always presented in a form that hid it from scrutiny. The failure to recognize it was not a failure of observation but a consequence of the invisibility of the disease. Historians of medicine are surprised that so few cases were recognized in Brazil. They fail to see that many cases also went undetected in Argentina, where hundreds of cases were later found. Throughout the latency period, rigid limits had been imposed on the study of Chagas disease, hiding it from view. No one imagined that a sign as common as facial swelling indicated anything other than thyroid insufficiency. Chagas was in no doubt about

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this; indeed, he thought that no other explanation was possible. With that mind-set, it was impossible to imagine that myxedema might be common to two different maladies. Paradoxically, it was because there was agreement about the nature of the most salient sign of the disease that different schools of physicians could not understand one another. In Brazil, Chagas ascribed the thyroid disorder to a parasitic infection spread by insects, implicitly assuming that the kind of goiter and cretinism observed in Europe did not exist there. Conversely, his opponents attributed thyroid insufficiency to a hereditary-infectious etiology, which meant that parasitic thyroiditis of the sort Chagas claimed to have observed in Lassance must not exist. Given this mind-set, debate did not revolve around the nature of the most salient sign of the disease but rather around the morbid entity that should be associated with that sign. The nature of the disease depended in an essential way on the specific nature of the etiological agent. In order to understand what was said on both sides of this controversy for a period of more than twenty years, it was essential first to recognize this fundamental division at the heart of medical thinking: Was Chagas disease classic hypothyroidism or parasitic hypothyroidism? Both sides agreed on the diagnosis of hypothyroidism and disagreed only about the etiology; neither recognized any other possibility. The history of Chagas disease is disconcerting. The first surprise is that Chagas never came closer to grasping the crucial point than at the beginning of his research, when he knew least about the disease. In the beginning, he thought that the crithidial forms were developmental forms of a trypanosome; he described the signs of a parasitosis (sub-palpebral edema, fever, enlarged lymph nodes); and he did not regard goiter as a symptom of the disease. But as the scientific elite poured more and more effort into research, their discoveries took them farther and farther away from Chagas’s initial perception. The lessons are clear: Initial intuitions are not always wrong, and the scientific community cannot always be relied on to prevent error. In the end, Chagas was able to formulate a theory of the disease, but he paid a high price: His achievement enshrined a bankrupt protozoology, an unrigorous clinical anatomy, and an old but updated etiological theory (of endemic goiter). The second surprise is the discovery that during the critical period, to which historians of medicine have granted so little credit, many important

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new issues were raised: There were questions concerning the life cycle of the parasite and its mode of transmission, the value of histopathological examinations, and the interaction of different disease entities. But the more different strategies for resolving each of these issues were tried, the greater the obstacles to identifying Chagas disease became. The proof that Chagas had mistakenly included symptoms of hypothyroidism in his description of the disease drew attention away from myxedema as its pathognomonic sign. By 1934, a peculiar situation had arisen: The only evidence in favor of Chagas disease was the parasitological diagnosis. It was more difficult than ever to perceive the disease clinically: Chagas disease was an enigma. The third surprise was that the sign that Romaña discovered seems so obvious to us that it is hard to believe that no one saw it before him. What Romaña did was not so much discover a sign as create the conditions under which it was possible for the sign to emerge. Instead of a medicine of pathogenic agents, what needed to be discovered was a medicine of pathological reactions. Then and only then could the pathogenic agent be fitted into a new picture of the disease. The discovery of a symptomatological detail proved decisive: Suddenly, hundreds of cases could be diagnosed at a glance, thanks to a simple sign: unilateral palpebral edema. The purpose of this essay was to show how Chagas disease could be interpreted as a history of traces. What do I mean by that? A trace is that which remains of a past that has left no trace. A trace refers to a complex operation: the invention of relations that allow an object, a theory, or a concept to emerge. First, an object: The discovery of the pathogenic parasite had nothing to do with Chagas’s experience of other vectorial diseases such as malaria. In order to find, observe, and describe Trypanosoma cruzi, he had to be assigned to a public health mission in Minas Gerais and to have received instruction in protozoology, in his case from members of the Schaudinn school. He had to relate two unrelated biological objects (the crithidial forms in the insect and Trypanosoma minasense) in order to accidentally discover a third object (Trypanosoma cruzi). Second, a theory: Chagas’s medical system fitted none of the paradigms of tropical medicine. It presumed an unprecedented combination of three things: a developmental cycle (anterior station), a thyroid syndrome, and an infectious etiology of goiter. This triad defined a framework that allowed

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the entity known as parasitic thyroiditis to emerge as a parasitic theory of goiter in Minas Gerais. Finally, a concept: The revelation of the oculo-palpebral syndrome did not mark the culmination or consequence of the immediately preceding state of knowledge. In order to describe it, Romaña had to bring together a geographical region, a hospital, a developmental cycle (posterior station), and a symptom common to known trypanosomiases. These abstract and concrete ingredients were tied together in “conceptual bundles”: a priori forms of perception that have a function in scientific discourse but do not figure in them explicitly, because scientific discourse itself depends on them. In homage to Michel Foucault, one might say that what we have here is an example of the “epistemonomic functioning” of medicine, which is realized in practices. If traces define “ways of acting,” then writing their history can only mean following the action. But since they are invisible, we must follow them as they emerge into visibility, at the moment they are first described. Their theoretical locus is therefore in the historical analysis that produces them. The object of a history of traces is the never foreordained history of norms of “effectuality,” the successive figures of which describe a series of traces. Traces are the unpredictable and varied lineaments of a series of “conceptual bundles” in the sense defined above—bundles that shape the transformations, grammatical rules, and epistemological limits of what can be said.

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notes

foreword: the false cannot be the moment of the true

1. François Delaporte, “Chagas Today,” Parassitologia 47, no. 3–4 (2005): 319–327. The essay, in part, is a response to critiques of La maladie de Chagas: Histoire d’un fléau continental (Paris: Payot, 1999). 2. Ilana Löwy, “The Controversy of the Early History of Chagas Disease,” Parassitologia 47, no. 3–4 (2005): 329–333. 3. François Delaporte, “Romaña’s Sign,” Journal of the History of Biology 30 (1997): 357–366. 4. Georges Canguilhem, Ideology and Rationality in the History of the Life Sciences, trans. A. Goldhammer (Cambridge: MIT Press, 1988), 2. 5. Delaporte, “Chagas Today,” 325. 6. Gaston Bachelard, Le Matérialisme rationnel (Paris: PUF, 2000), 86, quoted in Georges Canguilhem’s essay, “The Role of Epistemology in Contemporary History of Science,” in his Ideology and Rationality, 11. introduction

1. Henrique de Souza Araujo, “Costumes paraenses—As habitações e costumes das populações do interior, do Gurupy ao Oyapock,” Brasil-Médico (1923), reprint, 5–6. 2. Ezequiel Dias, “Traços de Oswaldo Cruz,” Memórias do Instituto Oswaldo Cruz 15 (1922): 25–35. 3. Reginaldo Lizarraga de Ovando, Descripcion breve de toda la Tierra del Peru, Tucaman, Rio de la Plata y Chile. In Historiadores de Indias, Obras Completas. Madrid, 1909, 2: 544–645, in Francisco Guerra, “American Trypanosomiasis: An Historical and a Human Lesson,” reprinted from the Journal of Tropical Medicine and Hygiene 73 (April–May 1970): 83–118; reprint 3a.

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Notes to pages 6–17

4. Joseph Gumilla, El Orinoco Ilustrado: Historia natural, civil y geografica de este gran rio (Madrid, 1741), 426; in Francisco Guerra, “American Trypanosomiasis: An Historical and a Human Lesson,” reprinted from the Journal of Tropical Medicine and Hygiene 73 (April–May 1970): 83–118; reprint 3b. 5. Charles Darwin, Journal of Researches into the Geology and Natural History of the Various Countries visited by H.M.S. Beagle, under the command of Captain Fitzroy, R.N., from 1832 to 1836 (London, 1839), 403–404; in Francisco Guerra, “American Trypanosomiasis: An Historical and a Human Lesson,” reprinted from the Journal of Tropical Medicine and Hygiene 73 (April–May 1970): 83–118; reprint 4b. 6. Rodrigues Alves, “Mensagens presidenicais (1890–1910),” Câmara dos deputados: Documentos parlamentáres 9 (Brasília, 1978), 303–307, in Manguinhos do sonho a vida, coord. Jaime Benchimol (Rio de Janeiro, 1990), 23. 7. Carlos Chagas, “Oswaldo Cruz,” Memórias do Instituto Oswaldo Cruz (1916), in Oswaldo Cruz no julgamento dos contemporâeneos (Rio de Janeiro, 1972), 23. Chagas stressed this point as early as 1912. Cf. “Discurso pronunciado pelo Dr. Carlos Chagas,” VII Congresso brasileiro de medicina e cirurgia (Belo Horizonte, 1912), 4–5. 1. identifications

1. Matthias Perleth, Historical Aspects of American Trypanosomiasis (Chagas’ Disease) (Frankfurt am Main, 1997), 80–81. 2. Jaime Benchimol and Luis Teixeira, Cobras, lagartos e outros bichos (Rio de Janeiro, 1993), 50. 3. “Testamento de Oswaldo Cruz,” in Oswaldo Cruz, Opera Omnia (Rio de Janeiro, 1972), 740. 4. Gilberto Freire, Casa grande e Senzal, in L. Cunha, O ensino superior de Colônia à Era de Vargas: Educação e transformação (Rio de Janeiro, 1980), 117. 5. Letter from Pasteur to the emperor of Brazil, Sept. 22, 1884, in Daniel Raichvarg, Éthique médicale et Droits de l’homme (Paris, 1988), 164–165. 6. Oswaldo Cruz, “A vehiculação microbiana pelas aguas,” these apresentado à Facultade de Medicina do Rio de Janeiro em 8 de Novembro de 1892 (Rio de Janeiro, 1893), in Opera Omnia (Rio de Janeiro, 1972), 23. 7. Oswaldo Cruz, “Uma visita à seção de preparo dos sôros therapeuticos” Brasil-Médico, 1898, in Opera Omnia (Rio de Janeiro, 1972), 285–286. 8. Oswaldo Cruz, Relatoria acerca da moléstia reinante em Santos, 1900, in Opera Omnia (Rio de Janeiro, 1972), 332. Pedro de Affonso’s letter is quoted in T. Fernandes, “Oswaldo Cruz X Barão de Pedro Affonso: polemica no controle de imunizantes,” Cadernos de Casa Oswaldo Cruz (1989): 1, 34a. 9. Henrique de Beaurepaire Aragão, “Noticia Histórica sobre a fundação do Instituto Oswaldo Cruz,” Memórias do Instituto Oswaldo Cruz 48 (1950): 11.

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Notes to pages 18–27

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Cf. Oswaldo Cruz, “A vaccinação anti-pestosa,” Brasil-Médico (1901), in Opera Omnia (Rio de Janeiro, 1972), 373–375. In a previous work, Cruz had already mentioned this fictitious affiliation: “Contribuição para o estudo dos culicidios de Rio de Janeiro” (Trabalho do Instituto de Manguinhos), Brasil-Médico (1901), in Opera Omnia (Rio de Janeiro, 1972), 363–372. 10. Quoted in Nancy Stepan, Gênese e Evolução da Ciência Brasileira (Rio de Janeiro, 1976), 78. 11. A. Normand, L’architecture des nations étrangéres (Paris, 1870), 42b. See also A. Chirac, L’exposition universelle de 1867: Illustrée, International Publication Authorized by the Imperial Commission (Paris, 1867), 39c–42b. The Moorish style is common in Latin America. See, for example, the work of Aldunate in Chile (including a parody of the Alhambra for a wealthy mine owner and the façade of the Recoleta Dominica) and of Teodore Burchard (the Diaz Gana palace in Santiago, Chile). 12. Eurico Villela, Carlos Chagas (Rio de Janeiro, 1959), 49. This version of story has been repeated more recently by Carlos Chagas Filho, Meu Pai (Rio de Janeiro, 1993), 82. 13. Perleth, Historical Aspects, 92. 14. Rachel Lewinsohn, “Carlos Chagas and the Discovery of Chagas’s Disease (American Trypanosomiasis),” Journal of the Royal Society of Medicine 74 (1981): 454. See also Benjamin Harrison Kean, “Carlos Chagas and Chagas’ Disease,” American Journal of Tropical Medicine and Hygiene 26 (1977): 1085a. 15. John Leonard, “Carlos Chagas, Pionero de la salud en el interior del Brasil,” Boletin de la Oficina Sanitaria Panamericana 110 (1991): 189b. This idea already appears in Evandro Chagas; see “Comentarios sobre la vida e a obra de Carlos Chagas,” Novena reunión de la Sociedad argentina de patología regional 103 (Mendoza, Argentina, 1935): 121. 16. Villela, Carlos Chagas, 49. See also Alicia Buttner, “Un aspect inconnu de Brésil: L’oeuvre de Carlos Chagas (1879–1934),” O Hospital 48 (1955): 510. 17. Rachel Lewinsohn, “Carlos Chagas (1879–1934): The Discovery of Trypanosoma cruzi and of American Trypanosomiasis,” Transactions of the Royal Society of Tropical Medicine and Hygiene 73 (1979): 513b. 18. Emile Brumpt, Précis de parasitologie, 2nd ed. (Paris, 1913), 165. 19. Cecil Hoare, The Trypanosomes of Mammals (London, 1972), 191. 20. L. Deane, J. da Silva, and L. Lures Filho, “Nycthemeral variation in the parasitaemia of Trypanosoma minasense in naturally infected Marmosets of the genus Callithrix (Primates, Callithricidae),” Revista do Instituto de medicina tropical de São Paulo 16 (1974): 6. 21. Carlos Chagas, “Descoberta do Tripanosoma cruzi e verificação da Tripanosomíase Americana: Retrospecto Historico,” Memorias do Instituto Oswaldo Cruz (1922), in Coletânea de trabalhos cientificos (Brasilia, 1981), 600.

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Notes to pages 27–35

22. Carlos Chagas, “Nova tripanossomíase humana,” Memórias do Instituto Oswaldo Cruz (1909) in Coletânea de trabalhos cientificos (Brasilia, 1981), 12. 23. Carlos Chagas, “Nova entidade morbida do homen,” Memorias do Instituto Oswaldo Cruz 2 (1911), in Coletânea de trabalhos cientificos (Brasilia, 1981), 111–112. This experiment reflected Chagas’s hypothesis, which was incompatible with two others: a parasite of the insect itself or a parasite of humans and domestic animals. The latter could have been verified on the spot. 24. Carlos Chagas, “O mal de Chagas,” Arquivos da Sociedade de medicina e cirurgia (1912), in Coletânea de trabalhos cientificos (Brasilia, 1981), 197. The same information had already been given two years earlier. Cf. Carlos Chagas, “Nova entidade morbida do homem,” 1910, in Coletânea de trabalhos cientificos (Brasilia, 1981), 90: “After a few days, [the monkey] showed a trypanosome in its peripheral blood.” 25. Carlos Chagas, “Trypanosomiase Americana: Uma rectifição do Dr Chagas a conferencia do Dr F. de Vasconcellos,” Jornal do comércio, August 23, 1919, 6c–7a. 26. Carlos Chagas, “Neue Trypanosomen: Vorläufige Mitteilung,” Archiv für Schiffs- und Trophenhygiene 13 (1909): 120–121 (emphasis added). See also Carlos Chagas, “Nova tripanossomiase humana,” Imprenta Médica (São Paulo) 10 (1909): 154–155. Chagas always indicated that it was he who obtained experimental infections in dogs, guinea pigs, and rabbits. 27. Oswaldo Cruz, “Algumas moléstias produzidas por protozoarios,” Conferencia feita na Bibliotheca Nacional, 1915, in Opera Omnia (Rio de Janeiro, 1972), 732. If Cruz wrote “a few days,” it was because this was what he meant. Chagas twice ignored this information. See n. 24 above. 28. Carlos Chagas, “Nova especie morbida do homem, produzida por um tripanossoma (Trypanosoma cruzi),” Brasil-Médico 16 (1909): 227a. See also Carlos Chagas, “Uma nova tripanossomíase humana,” Brasil-Médico 17 (1909): 175b; and “Über eine neue Trypanosomiasis des Menschen: Zweite vorläufige Mitteilung,” Archiv für Schiffs- und Tropenhygiene 13 (1909): 351–53, in Coletânea de trabalhos cientificos (Brasilia, 1981), 5. 29. Chagas, “Nova tripanossomíase humana,” 12. 30. Chagas, “Neue Trypanosomen,” 120. 31. Carlos Chagas, “Nouvelle espèce de trypanosomiase humaine,” Bulletin de la Société de pathologie exotique 6 (1909): 304–305. 32. Chagas, “Nova especie morbida do homen,” 227b. 33. Chagas, “Uma nova tripanossomíase humana,” 176a. 34. Chagas, “Nova especie morbida do homen,” 227b. 35. Chagas, “Nova tripanossomíase humana,” 16. The second child was eight years old and not two, as Chagas wrote. The diagnosis in the third case

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Notes to pages 36–52

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was based not on identification of the trypanosome but on observation of schizogonic forms in the lungs. 36. Quoted in Renato Clark Bacellar, Carlos Chagas (Rio de Janeiro, 1953), 11. 37. Clementino Fraga, “Nova entidade morbida do homem descoberta e estudada pelo Dr Carlos Chagas,” Gazeta médica da Bahia 47 (1911): 204–205. 38. Carlos Chagas, Moléstia de Carlos Chagas ou tiróidite parasitaria (second lecture at the National Academy of Medecine) (Rio de Janeiro, 1911), 3. 39. Bento Cruz, “Letter of December 19, 1922, to Professor Miguel Couto, president of the National Academy of Medicine,” A Folha Médica 25 (1923): 25c. 40. Chagas, “Nova entidade morbida do homem,” 112. 41. Cruz, “Algumas moléstias produzidas por protozoarios,” 731–732. 42. Chagas, “O mal de Chagas,” 197–198. Subsequent versions would combine this idea with the claim that a novel pathology had been identified at the outside. We will see that these two ideas are not contradictory. 43. Cruz, “Algumas moléstas produzidas por protozoarios,” 732. 44. Chagas, “O mal de Chagas,” 197–198. Two variants of this account appear in subsequent versions: “A few days” became two or three weeks, and Chagas himself took credit for the discovery of the trypanosome. “Fifteen to twenty days after the contact with the insect, one of these monkeys showed symptoms of an infection, including acute keratitis. While examining the blood of this animal, we discovered a trypanosome.” See Carlos Chagas, La tripanosomiase américaine: Étude du parasite et de son insecte intermédiaire (Rio de Janeiro, 1923), 4a. 45. Cruz, “Algumas moléstias produzidas por protozoarios,” 731. 46. Belisário Penna, Saneamento do Brasil (Rio de Janeiro, 1918), 22. 2. system

1. J. L. Minoprio, “Consideraciones sobre los trabajos originarios del Dr Carlos Chagas,” Boletín de la Academia nacional de medicina 57 (1979): 335. 2. Emile Marchoux, “Notice nécrologique sur Carlos Chagas,” Bulletin de l’Académie de médecine (1934), reprint, 4. 3. Olympio da Fonseca Filho, A Escola de Manguinhos (São Paulo, 1974), 45b. 4. Matthias Perleth, Historical Aspects of American Trypanosomiasis (Chagas’ Disease) (Frankfurt am Main, 1977), 94. 5. Carlos Chagas, “Nova tripanossomíase humana,” Memorías do Instituto Oswaldo Cruz (1909), in Coletânea de trabalhos cientificos (Brasilia, 1981), 73–77. 6. Ibid., 69. In 1974, the historian Olympio da Fonseca Filho pointed to the role of German protozoology. See A Escola de Manguinhos, 46a–48b. 7. Chagas, “Nova tripanossomíase humana,” 25.

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Notes to pages 52–65

8. Henrique de Beaurepaire Aragão, “Sobre o ciclo evolutivo do halteridio do pombo (2e Nota),” Brasil-Médico 31 (1907): 303a. See also “Nota preliminar,” Brasil-Médico 15 (1907): 139a–140a. No other author confirmed Schaudinn’s research on the direct penetration of red blood cells by sporozoites. Aragão here described a primary schizogony, the “exo-erythrocytic cycle.” 9. Chagas, “Nova tripanossomíase humana,” 55. This idea was shared by Max Hartmann. See “Notiz über eine weitere Art der Schizogonie bei Schizotrypanum cruzi (Chagas),” Archiv für Protistenkunde 20 (1910): 361–363. 10. Chagas, “Nova tripanossomíase humana,” 43. 11. Ibid., 65. 12. Gaspar Vianna, “Contribução para o estudo da anatomia patológica da ‘Moléstia de Carlos Chagas,’ ” 1911, in Opera Omnia de Gaspar Vianna (Rio de Janeiro, 1962), 324. 13. M. and Mme Pierre Delanoë, “Sur les rapports des kystes de Carini du poumon des rats avec le Trypanosoma lewisi,” Comptes rendus de l’Académie de sciences 7 (1912): 660. 14. Henrique de Beaurepaire Aragão, “Nota sobre as schizogonias e gametogonias dos tripanosomas,” Brasil-Médico (1913), reprint, 3. 15. Carlos Chagas, “Revision of the Life Cycle of ‘Trypanasoma cruzi,’ Supplementary Note,” Brasil-Médico (1913), in Coletânea de trabalhos cientificos (Brasilia, 1981): 241. 16. Carlos Chagas, Moléstia de Carlos Chagas ou tireódite parasitaria, second lecture at the National Academy of Medicine (Rio de Janeiro, 1911), 7. 17. Carlos Chagas, “Nova entidade morbida do homen,” 1911, in Coletânea de trabalhos cientificos (Brasilia, 1981), 163. 18. Chagas, “Nova tripanossomíase humana,” 17–19. 19. Chagas, “Nova entidade morbida do homem,” 94. See also “Sobre a etiologia do bocio endemico no Estado de Minas Gerais,” Brasil-Médico (1910), reprint, 3: “Our attention was drawn by the constant hypertrophy of the thyroid gland in children infected by the Schizotrypanum. . . . In cases of acute infection, one must also add myxedema.” See also Moléstia de Carlos Chagas ou tireóidite parasitaria, Conferencia realisada perante a Associação Médico Cirurgica de Minas Gerais (Rio de Janeiro, 1911), 17. 20. Chagas, Moléstia de Carlos Chagas, second lecture, 9. 21. Vianna, “Contribução,” 325. See also Chagas, “Nova entidade morbida do homem,” 94, 99. 22. Chagas, “Sobre a etiologia,” 4. The description of the various syndromes dates from 1910. See Chagas, “Nova entidade morbida do homem,” 96–102. 23. Chagas, “Sobre a etiologia,” 3. 24. Chagas, “Nova entidade morbida do homem,” 104. Cf. Robert McCarrison, “Further Researches on the Etiology of Endemic Goiter,” Quarterly Journal of Medicine 2 (1908–1909): 285–287.

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Notes to pages 66–73

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25. Paul Jeandelize, Insuffisance thyroïdienne et parathryoïdienne (Paris, 1904), 623. Carlos Chagas might have consulted this work, which Oswaldo Cruz had in his library. 26. Edouard Chatton and R. Courrier, “Un Schizotrypanum chez les chauvessouris (Versperugo pipstrellus) en Basse-Alsace: Schizotrypanose et goitre endémique,” Comptes rendus de la Société de biologie 84 (1921): 946. Cf. M. Bouilliez, “Contribution à l’étude et à la répartition de quelques affections parasitaires au Moyen-Chari (Afrique central),” Bulletin de la Société de pathologie exotique 9 (1916): 167. See also Ernest de Bergevin and Étienne Sergent, “À propos de l’hypothèse de la transmission du goitre endémique par un insecte piqueur,” Bulletin de la Société de pathologie exotique 10 (1916): 345. 27. Chagas, Moléstia de Carlos Chagas, second lecture,14–15. Chagas often compared American trypanosomiasis to syphilis. See Chagas, “Nova entidade morbida do homem,” 94. 28. Chagas, “Nova entidade morbida do homem,” 103. 29. Carlos Chagas, “Sobre um tripanossoma do tatu, Tatusia novemcincta, transmittido pela Triatoma geniculata Latr. (1811). Possibilidade de ser o tatu um depositário do Trypanosoma cruzi no mundo exterior,” Brasil-Médico (1912), in Coletânea de trabalhos cientificos (Brasilia, 1981), 228. 30. Arthur Neiva, “Informações sobre a biologia do Conorhinus megistus Brum,” Memórias do Instituto Oswaldo Cruz (1910), in Triatomideos Coletânea (Rio de Janeiro, 1944), 4: 2–5. 31. Arthur Neiva, “Da transmissão do Trypanosoma cruzi pela Triatoma sordida Stal,” Brasil-Médico (1913), in Triatomideos Coletânea (Rio de Janeiro, 1944), 4:37. On the vectors of the parasite, see Arthur Neiva, “Revisão do gênero Triatoma Lap,” 1914, in Triatomideos Coletânea (Rio de Janeiro, 1944), 4: 53–98. And E. Brumpt, “Réduvides de l’Amérique du Nord capables de transmettre le Trypanosoma cruzi,” Bulletin de la Société de pathologie exotique 6 (1914): 132–133. 32. Arthur Neiva, “Penetração do Trypanosoma evansi a través da conjuntiva da cobaia (nota prévia).” Brasil-Médico (1913), reprint, 104. 33. Eurico Villela, “Bocio endemico,” Revista brasileira de medicina 10 (1953): 211. 3. revisions

1. Jaime Benchimol and Luis Teixeira, Cobras, lagartos e outros bichos (Rio de Janeiro, 1993), 56–59. 2. Carlos Chagas Filho, “Historico sobre doença de Chagas,” in Doença de Chagas, ed. J. Romeu Cançado (Belo Horizonte, 1968), 12. 3. Eurico Villela, “Carlos Chagas e sua projeção no estrageiro,” A Folha Médica 25 (1936): 298b.

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Notes to pages 74–85

4. E. Minchin and J. Thomson, “On the Occurrence of an Intracellular Stage in the Development of Trypanosoma lewisi in the Rat-Flea,” British Medical Journal 2 (1911): 363b. 5. Martin Mayer and Henrique da Rocha Lima, “Zum Verhalten von Schizotrypanum cruzi in Warmblütern und Arthropoden,” Archiv für Schiffs- und Tropenhygiene 18 (1914): 124. Eucario Novaes reached the same conclusions. See “La tripanossomíase brésilienne et son rapport avec le corps thyroïde,” Revue médicale de la Suisse romande 36 (1916): 610. 6. Robert McCarrison, “The Milroy Lectures on the Etiology of Endemic Goitre,” Lancet 1 (1913): Lecture 3, 365b; Kolle’s experiment was reported by McCarrison, 365b. See also Antonio Carini, “Contributo sperimentale alla etiologia del cretinismo,” Pathologica 5 (1912): 172a. 7. Nicolas Lozano, “La enfermedad de Chagas,” Archivo de higiene 4 (1911): 125. 8. Emile Brumpt, “Immunité partielle dans les infections à Trypanosoma cruzi, transmission de ce trypanosome par Cimex rotundatus: Rôle régulateur des hôtes intermediaries: Passage à travers la peau,” Bulletin de la Société de pathologie exotique 6 (1913): 175. 9. Rudolph Kraus, Carlos Maggio, and Francisco Rosenbusch, “Bocio, cretinismo y enfermedad de Chagas (Primera comunicación),” La Prensa médica argentina 1 (1915): 5a. 10. Ibid., 2b. 11. Emile Brumpt, “Évolution de Trypanosoma lewisi, duttoni, nabiasi, blanchardi, chez les puces et les punaises: Transmission par les dejections: Comparaison avec T. cruzi,” Bulletin de la Société de pathologie exotique 6 (1913): 167–168. 12. Emile Brumpt, “Le Trypanosoma cruzi évolue chez Conorhinus megistus, Cimex lectularius, Cimex boueti et Ornithodorus moubata: Cycle évolutif de ce parasite,” Bulletin de la Société de pathologie exotique 5 (1912): 360–361. 13. Emile Brumpt, “Immunité partielle dans les infections à Trypanosoma cruzi, transmission de ce trypanosome par Cimex rotundatus: Rôle régulateur des hôtes intermediaries: Passage à travers la peau,” Bulletin de la Société de pathologie exotique 6 (1913): 173–174. In note 1, Brumpt pointed out that he infected a three-week-old lamb by depositing ground-up triatomids on the mucous membranes of the mouth. 14. Kraus, Maggio, and Rosenbusch, “Bocio, cretinismo y enfermedad de Chagas (Primera comunicación),” 4b–c. 15. Rudolph Kraus and Francisco Rosenbusch, “Bocio, cretinismo y enfermedad de Chagas (Segunda comunicación),” La Prensa médica argentina 17 (1916): 178b. 16. Kraus, Maggio, and Rosenbusch, “Bocio, cretinismo y enfermedad de Chagas (Primera comunicación),” 2c–3b.

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Notes to pages 86–92

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17. Carlos Chagas, “Nova entidade morbida do homen,” 1911, in Coletânea de trabalhos cientificos (Brasilia, 1981), 91a. 18. Carlos Maggio and Francisco Rosenbusch, “Estudio de los Trypanosomas de las vinchucas de la República Argentina,” Annales del Departamento nacional de higiene 21 (1914): 222. 19. Kraus, Maggio, and Rosenbusch, “Bocio, cretinismo y enfermedad de Chagas (Primera comunicación),” 5a–b. See also Kraus and Rosenbusch, “Bocio, cretinismo y enfermedad de Chagas (Segunda comunicación),” 178b. 20. Francisco Rosenbusch, “Comisión de investigación sobre bocio, cretinismo y enfermedad de Chagas en la provincial de Salta,” Anales del Departamento nacional de higiene 23 (1916): 119–123 (italics added). 21. Carlos Chagas, “Aspectos clínicos y anatomo patológicos de la Tripanosomiasis americana,” La Prensa médica argentina (1916), in Coletânea de trabalhos cientificos (Brasilia, 1981), 259. See Carlos Chagas, “Processos patogénicos da tripanossomíase Americana,” 1916, in Coletânea de trabalhos cientificos (Brasilia, 1981), 387: “We hope especially in this chapter to eliminate any confusion in the clinical criteria that may have been occasioned by shortcomings in previous publications.” 22. Carlos Chagas, Résumé de l’étiologie et des aspects cliniques de la trypanosomiase américaine (Rio de Janeiro, 1920), 8b. See Carlos Chagas and Carlos B. de Magarinos Torres, “Fecundação num flagelado de vida livre Prowazeckia cruzi, Hartmann et Chagas,” Brasil-Médico 29 (1916): 224a–b. In 1916, Chagas recalled the denomination of Lutz, taken from the realm of transmission: “Choreotrypanosis.” 23. Chagas, “Processos patogénicos,” 392. See also Carlos Chagas, “Tripanossomíase Americana: Forma aguda da moléstia,” Memórias do Instituto Oswaldo Cruz, 1916, in Coletânea de trabalhos cientificos (Brasilia, 1981), 310. 24. L. Chaves, “Processos distroficos na moléstia de Carlos Chagas,” Memórias do Instituto Oswaldo Cruz 7 (1915): 205a. 25. Chagas, “Aspectos clínicos,” 393. 26. Ibid., 413. Ultimately, Chagas could accept that he had been wrong to speak of a parasitic etiology of goiter, but on the subject of the acute form he stood his ground. Cf. page 394: “Even if we were in error as to the etiology of goiter, we stand by the assertion that myxedema is the most predominant sign in the description of acute cases.” 27. Juan Segovia, “Un caso de Trypanosomiasis,” Archivo del Hospital Rosales 8 (1913): 252–253. This encounter reoriented the investigation toward a search for the propagating insect. Segovia subsequently described the vector, and Neiva immediately classified the bug as Triatoma dimidiata Latreille. In 1922, Segovia described a second case, also encountered accidentally. See Juan Segovia, Trypanosomiasis en el Salvador (San Salvador, 1922), 1–19. Wurtz and Tanon proposed the name Trypanosoma cruzi, Segovia variety.

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Notes to pages 92–103

28. Edmundo Escomel, “La tripanossomíase humaine existe dans les forêts orientales du Pérou,” Bulletin de la Société de pathologie exotique 12 (1919): 724. Debate broke out about whether the parasite was in fact Trypanosoma cruzi: Because it was larger in size, Yorke proposed to call it Trypanosoma escomeli, but Brumpt and Mesnil challenged this denomination. 29. Eurico Villela, “Forma aguda da moléstia de Chagas: Primeira verificação no Estado de São Paulo,” Brasil-Médico 32 (1918): 65. 30. Arthur Neiva, “Presença em uma localidade do Estado do Rio de um novo transmissor da ‘Moléstia de Chagas’ encontrado infectado em condições naturaes,” Brasil-Médico (1914), in Triatomideos Coletânea (Rio de Janeiro, 1944), 4:102. Cf. Emile Brumpt, “Le xénodiagnostic: Application au diagnostic de quelques infections parasitaires et en particulier à la trypanosomiase de Chagas,” Bulletin de la Société de pathologie exotique 7 (1914): 706–710. 31. Paulo Parreiras Horta, Boletim da Academia nacional de medicina 20 (1923): 698–704, session of November 22, 1923. 32. Ibid., 707. 33. Henrique de Beaurepaire Aragão, Alguns problemas relatives a prophylaxia das endemias ruraes no Brasil (Rio de Janeiro, 1919), 8–9. 34. Afrânio Peixoto, Boletim da Academia nacional de medicina (1922): 723, in L. Ribeiro, Afranio Peixoto (Rio de Janeiro, 1950), 191. 35. Carlos Chagas, Boletim da Academia nacional de medicina (Rio de Janeiro) (1922): 768, session of December 14, 1922. 36. Figueiredo Vasconcellos, Moléstia de Cruz e Chagas (Rio de Janeiro, 1919), 46. 37. Figueiredo Vasconcellos, Boletim de Academia nacional de medicina (Rio de Janeiro) (1923): 678, session of November 8, 1923. 38. Vasconcellos, Moléstia de Cruz e Chagas, 4–6. 39. Figueiredo Vasconcellos, Boletim de Academia nacional de medicina (Rio de Janeiro) (1923): 771. session of November 23, 1923. 40. Vasconcellos, Moléstia de Cruz e Chagas, 17. 41. Carlos Chagas, “Descoberta do Tripanosoma cruzi e verificação da Tripanossomíase Americana: Restrospecto Historico,” Memórias do Instituto Oswaldo Cruz (1922), in Coletânea de trabalhos cientificos (Brasilia, 1981): 600–602. 42. Carlos Chagas, “Informações prestadas pelo Dr. Carlos Chagas a Academia de medicina,” Arquivos brasileiros de medicina 14 (1924): 87–88. 4. recasting

1. Rodolf Talice, F. Medina, and F. Rial, “Primer caso de enfermedad de Chagas en el Uruguay,” Anales de la Facultad de Medicina de Montevideo

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Notes to pages 103–13

149

22 (1937): 238. See also Octavio de Magalhaes, “Un poco da vida de Carlos Chagas,” Memória do instituto biológico Ezequiel Dias 4 (1942): 3–16. 2. Carlos B. de Magarinos Torres, “En homenaje al prof. Salvador Mazza,” Suplemento de La Semana médica, Sept. 21, 1949, quoted by Jobino Pedro Sierra Iglesias, Salvador Mazza (San Salvador de Jujuy, 1990), 347. 3. Matthias Perleth, Historical Aspects of American Trypanosomiasis (Chagas’ Disease) (Frankfurt am Main, 1977), 103. 4. Louis Nattan-Larrier, “Hérédité des infections expérimentales à Schizotrypanum cruzi,” Bulletin de la Société de pathologie exotique 14 (1921): 238. 5. Julio Muniz, “Quelques forms intéressantes trouvées dans des cultures de Trypanosoma cruzi,” Comptes rendus de la Société de biologie 97 (1927): 823. See Carlos Chagas, “Quelques aspects évolutifs du Trypanosoma curzi dans l’insecte transmetteur,” Comptes rendus de la Société de biologie 97 (1927): 832. 6. Elbert de Coursey, “The First Fatal Case of Chagas’ Disease Observed on the Isthmus of Panama,” American Journal of Tropical Medicine 15 (1935): 36. 7. Arthur Penna de Azevedo, “Histologia patológica da glandula tireóide na forma aguda da Moléstia de Chagas,” Memórias do Instituto Oswaldo Cruz 27 (1933): 119. 8. Salvador Mazza, “Caso de esquizotrypanosis humana observado en la ciudad de Jujuy (nota preliminar),” Revista de la Sociedad argentina de biologia 1 (1925): 84. 9. Flavio Niño, “A proposito de un nuevo caso de enfermedad de Chagas en la República Argentina,” Cuarta reunion de la Sociedad argentina de patología regional del Norte (Buenos Aires) (1928): 581. 10. J. Lacorte, “A reacção do desvio do complemento na Moléstia de Chagas,” Memórias do Instituto Oswaldo Cruz 20 (1927): 201a. 11. J. Baeta Vianna, “Bocio endemico em Minas Gerais,” Anais da Faculdade de medicina de Minas Gerais 3 (1931): 56. 12. A. Lobo Leite, “Communication faite à la Société brésilienne de biologie,” 1933, in Cecilio Romaña, “Trypanosomiasis americana y bocio endémico,” La Semana médica 42 (1935): 901a–901b. See also A. Lobo Leite, “Doença de Chagas e bocio endemico,” Brasil-Médico 46 (1939): 1031a–1033a. 13. Eurico Villela, “Da ocorrência da doença de Chagas nos hospitaes de Belo Horizonte e na população de seus arredores,” A Folha Médica 11 (1930): 235b. 14. Ibid., 229b. See also Emmanuel Dias, “Persistance de l’infection par le Schizotrypanum cruzi chez l’homme,” Comptes rendus de la Société de biologie 117 (1932): esp. 506–507: “Patient from Affonso-Penna asylum. Mental retardation, deaf-mute. Goiter. Increased heart volume. Positive Machado reaction.” 15. Emmanuel Dias, “Estudos sobre o Schiztrypanum cruzi,” Memórias do Instituto Oswaldo Cruz 28 (1935): 91.

Delaporte-Notes.indd 149

6/27/2012 2:30:33 PM

150

Notes to pages 113–27

16. Emmanuel Dias, “Le xénodiagnostic appliqué à la trypanosomiase américaine,” Comptes rendus de la Société de biologie 118 (1935): 287. 17. Emmanuel Dias, “O ‘Signal de Romaña’ e os novos progressos no estudo da doença de Chagas,” A Folha Médica 17 (1936): 345b–346b. 18. Dias, “Le xénodiagnostic,” 288. 19. Cecilio Romaña, “Novas investigações sobre a moléstia de Chagas na República Argentina,” Revista médico-cirúrgica do Brasil 9–10 (1934): 302. 20. Cecilio Romaña, “Comprobación de formas agudas de tripanosomiasis americana en el Chaco austral y santafecino,” MEPRA 14 (1934): 3. 21. Cecilio Romaña, “Trypanosomiasis americana y bocio endémico,” La Semana médica 42 (1935): 901b. 22. Cecilio Romaña, “Acerca de un sintoma inicial de valor para el diagnostico de forma aguda de la enfermedad de Chagas,” MEPRA 22 (1935): 25–26. 23. Ibid., 17. Romaña had already made the same observation in his first paper. See “Comprobación de formas agudas de tripanosomiasis americana,” 15. 24. Romaña, “Acerca de un sintoma inicial,” 28. 25. Emile Brumpt, Précis de parasitologie, 5th ed. (Paris, 1936), 354. 26. Salvador Mazza and A. Ruchelli, “Comprobación de dos casos agudos de enfermedad de Chagas en Tinogasta” (Catamarca), La Prensa médica argentina 20 (1934): 3. See also Cecelio Romaña, “Nuevas comprobaciones de formas agudas puras de enfermedad de Chagas en el norte santafecino,” MEPRA 20 (1934): 30. 27. Rodolfo Talice, Enfermedades parasitarias del hombre (Montevideo, 1944), 409. 28. Ramón Carillo, “Primera conferencia nacional de la enfermedad de Chagas (Buenos Aires, 1953),” in Jobino Pedro Sierra Iglesias, Salvador Mazza, su vida, su obra, redsucbridor de la enfermedad de Chagas (San Salvador de Jujuy, 1990), 350. 29. Henrique de Souza Araujo, “Congreso internacional sobre la enfermedad de Chagas (Rio de Janeiro, 1959),” in Sierra Iglesias, Salvador Mazza, 353. 30. Germinal Basso, Redento Basso, and Alberto Bibiloni, Investigaciones sobre la enfermedad de Chagas-Mazza (Buenos Aires, 1978), xi. 31. Emmanuel Dias, “Xenodiagnostico e algunas verificacções epidemiologicas na moléstia de Chagas,” Novena reunión de la Sociedad argentina de patologia regional (Buenos Aires) (1935): 106. 32. F. Pick, “Sur le ‘Signe de Romaña,’ ” Acta tropica 11 (1954): 105. 33. Salvador Mazza, “Sobre el valor del edema palpebral de un solo lado para el diagnostico de forma aguda de la Enfermedad de Chagas,” Novena reunión de la Sociedad argentina de patología regional (Buenos Aires) (1935): 343–345. See also the photographs accompanying the Spanish translation of

Delaporte-Notes.indd 150

6/27/2012 2:30:33 PM

Notes to pages 128–31

151

Chagas’s paper, “Tripanosomiasis Americana, forma aguda de la enfermedad,” MEPRA 55 (1941): 3–45. 34. Salvador Mazza, “Inexistencia de un sintoma patognomonico en formas agudas de Enfermedad de Chagas,” La Prensa médica argentina 1939, reprint, 5–7. 35. Flavio Niño, Contribución al estudio de la enfermedad de Chagas o tripanosomiasis americana (Buenos Aires, 1929), 207. 36. Mazza, “Sobre el valor del edema palpebral,” 345. 37. E. Dias, “O signal de Romaña e sua influencia na evolução dos conhecimentos sobre a moléstia de Chagas,” Brasil-Médico 42 (1939): 969a–b. See also Evandro Chagas and Emmanuel Dias, “A proposito do sinal de Romaña,” O Hospital 19 (1941): 185–189. 38. R. Caceres and A. Izaguirre, “Primer caso de forma aguda de enfermedad de Chagas determinado en la Provincia de Entre Ríos y Litoral argentine,” MEPRA 25 (1935): 19, quoted in Dias, “O signal,” 967a. 39. Mazza, “Inexistencia de un sintoma patognomonico,” 26. 40. Cecilio Romaña, Réplica (Tucamán, 1944), 25. 41. Cecilio Romaña, “Reproduction chez le singe de la ‘conjonctivite schizotrypanosomienne unilatérale,’ ” Bulletin de la Société de pathologie exotique 32 (1939): 392; see also “Le parasitisme des cellules épithéliales de la conjonctive du singe,” Bulletin de la Société de pathologie exotique 32 (1939): 810–813.

Delaporte-Notes.indd 151

6/27/2012 2:30:33 PM

Delaporte-Notes.indd 152

6/27/2012 2:30:33 PM

bibliography

Academia Nacional de Medicina. Medicina no Brasil. Rio de Janeiro, 1940. Ackerknecht, Erwin H. History and Geography of the Most Important Diseases. New York, 1965. Addison, Thomas. “On the Constitutional and Local Effects of Disease of the Suprarenal Capsules.” London, 1855. Alexeieff, Alexis. “Sur quelques points de la structure des Binucléates de Hartmann.” Comptes rendus de la Société de biologie 69 (1910): 532–534. Alfaro, Gregorio. Semblanzas y Apología de Grandes Médicos. Buenos Aires, 1936. Alves, Rodrigues. “Mensagens presidenciais (1890–1910).” Câmara dos deputados: Documentos parlamentares (Braisilia) 9 (1978): 303–307. Amaral, Aristote do. “Carlos Chagas, 1879–1934.” Revista de biologia e higiene 5 (1934): 55–57. Aragão, Henrique de Beaurepaire. Alguns problemas relativos à profilaxia das endemias ruraes no Brasil. Rio de Janeiro, 1919. ———. “Carlos Chagas, Diretor de Manguinhos.” Memórias do Instituto Oswaldo Cruz 51 (1953): 1–10. ———. “Classificação dos hemosporideos.” Memórias do Instituto de Butantan 1 (1918–1919): 167–185. ———. “Homenagem à memoria de Carlos Chagas e Evandro Chagas.” Boletim de higiene e saúde pública 4 (1946): 5–7; 6 (1946): 3–7. ———. “Nota sobre as schizogonias e gametogonias dos tripanosomas.” BrasilMédico (1913). Reprint. ———. “Notícia histórica sobre a fundação do Instituto Oswaldo Cruz.” Memórias do Instituto Oswaldo Cruz 48 (1950): 1–51. ———. “Sobre o ciclo evolutivo do halteridio do pombo (nota preliminar).” BrasilMédico 15 (1907): 139a–140a. ———. “Sobre o ciclo evolutivo do halteridio do pombo (2e Nota).” Brasil-Médico 31 (1907): 301a–303a. 153

Delaporte-Bibliography.indd 153

6/27/2012 4:07:16 PM

154

Bibliography

Bacellar, Renato Clark. Brazil’s Contribution to Tropical Medicine and Malaria. Rio de Janeiro, 1953. ———. Carlos Chagas. Rio de Janeiro. 1938. Baeta Vianna, J. “Bocio endemico em Minas Gerais.” Anais da Faculdade de medicina de Minas Gerais 3 (1931): 53–73. Bagshawe, Sir Arthur. “Recent Advances in Our Knowledge of Sleeping Sickness.” Transactions of the Society of Tropical Medicine and Hygiene 4 (1910): 1–23. Baillarger, Jules. Enquête sur le goitre et le crétinisme. 2 vols. Paris, 1873. Balfour, Andrew, and Sir Robert Archibald. “Second Review of some Recent Advances in Tropical Medicine.” Fourth Report of the Wellcome Tropical Research Laboratories at the Gordon Memorial College. Khartoum, London, 1911. Basso, Germinal, Redento Basso, and Alberto Bibiloni. Investigaciones sobre la enfermedad de Chagas-Mazza. Buenos Aires, 1978. Bayma, Theodore. “Moléstia de Carlos Chagas (segunda nota sobre sua verificação parasitológica no homem, em São Paulo).” Anais paulistas de medicina e cirurgia 3 (1914): 57a–58b. ———. “Um caso de mixedema congênito. Apontamentos sobre a distribução do “Triatoma” no Estado de São Paulo.” Revista de medicina de São Paulo 16 (1913): 103–105. Benchimol, Jaime, coord. Manguinhos do sonho a vida: A ciência na Belle Epoque. Rio de Janeiro, 1990. Benchimol, Jaime, and Luis Teixeira. Cobras, lagartos e outros bichos. Rio de Janeiro, 1993. Bergevin, Ernest de, and Etienne Sergent. “À propos de l’hypothèse de la transmission du goitre endémique par un insecte piqueur.” Bulletin de la Société de pathologie exotique 10 (1916): 345. Blanchard, Maurice. “Généralités sur la trypanosomiase américaine.” Annales d’hygiène et de médecine coloniales 15 (1912): 772–780. ———. “Marche de l’infection à Schizotrypanum cruzi chez le cobaye et la souris.” Bulletin de la Société de pathologie exotique 8 (1912): 598–599. ———. “Sur un travail de M. le Dr E. Brumpt, intitulé: Etude expérimentale de la trypanosomiase américaine de C. Chagas.” Bulletin de l’Académie de médecine 117 (1912): 428–433. Bombois, E. “L’oeuvre de Carlos Chagas (1879–1934).” Le Progrès médical 83 (1955): 85. Borzone, R., and M. Coda. “Tercera observacíon de Trypanosomiasis americana en Argentina: Forma suprarenal de enfermedad de Chagas.” Revista de sanidad militar 24 (1925): 119–132. Bouilliez, Marc. “Contribution à l’étude et à la répartition de quelques affections parasitaires au Moyen-Chari (Afrique centrale).” Bulletin de la Société de pathologie exotique 9 (1916): 143–167.

Delaporte-Bibliography.indd 154

6/27/2012 4:07:16 PM

Bibliography

155

Boyd, John. “Sleeping Sickness: The Castellani-Bruce Controversy.” Notes and Records of the Royal Society of London 28 (1973): 93–100. Breinl, Anton, and Edward Hindle. “Observations on the Life History of Trypanosoma lewisi in the Rat Louse (Haematopinus spinulosus).” Annals of Tropical Medicine and Parasitology 3 (1910): 353–360. Britto, Nara. Oswaldo Cruz: A construção de um Mito na Ciência Brasileira. Rio de Janeiro, 1995. Bruce, Sir David. Further Report on the Tsetse-Fly Disease or Nagana, in Zululand. London, 1897. Bruce, Sir David, David Nabarro, and Edouard Greig. “Further Report on Sleeping Sickness in Uganda.” Report of the Sleeping-Sickness Committee 2 (1903): 11–88. Brumpt, Emile. “Évolution de Trypanosoma lewisi, duttoni, nabiasi, blanchardi, chez les puces et les punaises: Transmission par les déjections: Comparaison avec T. cruzi.” Bulletin de la Société de pathologie exotique 6 (1916): 167–171. ———. “Immunité partielle dans les infections à Trypanosoma cruzi, transmission de ce trypanosome par Cimex rotundatus: Rôle régulateur des hôtes intermédiaires: Passage à travers la peau.” Bulletin de la Société de pathologie exotique 6 (1913): 172–176. ———. “Importance du cannibalisme et de la coprophagie chez les réduviidés hématophages (Rhodnius, Triatoma) pour la conservation des trypanosomes pathogènes en dehors de l’hôte vertébré.” Bulletin de la Société de pathologie exotique 7 (1914): 702–706. ———. “Le Trypanosoma cruzi évolue chez Conorhinus megistus, Cimex lectularius, Cimex boueti et Ornithodorus moubata. Cycle évolutif de ce parasite.” Bulletin de la Société de pathologie exotique 5 (1912): 360–364. ———. “Le xénodiagnostic. Application au diagnostic de quelques infections parasitaires et en particulier à la tripanossomiase de Chagas.” Bulletin de la Société de pathologie exotique 7 (1914): 706–710. ———. “Pénétration du Schizotrypanum cruzi à travers la muqueuse oculaire saine.” Comptes rendus de la Société de biologie 5 (1912): 723–724. ———. Précis de parasitologie. 2nd ed. Paris, 1913. ———. Précis de parasitologie. 2 vols. 5th ed. Paris, 1936. ———. “Réduvides de l’Amérique du Nord capables de transmettre le Trypanomosa cruzi.” Bulletin de la Société de pathologie exotique 6 (1914): 132–133. ———. “Sur quelques espèces nouvelles de trypanosomes parasites des poissons d’eau douce, leur mode d’évolution.” Comptes rendus de la Société de biologie 60 (1906): 160–162. ———. “Trypanosomiase américaine ou maladie de C. Chagas.” In Nouveau Traité de médecine, fasc. 5, ed. G. Roger, F. Widal, and P. Teissier, 299–312. Paris, 1922.

Delaporte-Bibliography.indd 155

6/27/2012 4:07:16 PM

156

Bibliography

Brumpt, Emile, and F. Gomes. “Description d’une nouvelle espèce de Triatoma (T. chagasi) hôte primitif du Trypanosoma cruzi Chagas.” Anais paulistas de medicina e cirurgia 3 (1914): 73–77. Brumpt, Emile, and Gonzalez Lugo. “Présentation d’un réduviidé du Venezuela, le Rhodnius prolixus, chez lequel évolue Trypanosoma Cruzi” Bulletin de la Société de pathologie exotique 6 (1913): 382–383. Brumpt, Emile, and Manuel Piraja da Silva. “Existence du Schizotrypanum cruzi Chagas, 1909, à Bahia (Matta de São João). Biologie du Conorhinus megistus.” Bulletin de la Société de pathologie exotique 5 (1912): 22–26. Bruni, N. “Observations et recherches sur Trypanosoma lewisi et Schizotrypanum cruzi,” Bulletin de la Société de pathologie exotique 19 (1926): 791–793. Buchanan, S. “Note on developmental forms of Trypanosoma brucei (pecaudi) in the internal organs, axillary glands, and bone marrow of the gerbil (Gerbillus pygargus).” Proceedings of the Royal Society of London, S. B. 84 (1911): 161–164. Buttner, Alicia. “Un aspect inconnu du Brésil: L’oeuvre de Carlos Chagas (1879–1934).” O Hospital 48 (1955): 509–520. Caceres, R., and A. Izaguirre. “Primer caso de forma aguda de enfermedad de Chagas determinado en la provincia de Entre Rios y Litoral argentino.” MEPRA 25 (1935): 18–25. Campos, Francisco. “Le professeur Carlos Chagas.” La Vie médicale 15 (1934): p. 162 1083–1084. Canal-Feijoo, E. “Aspectos médico-sociales de la enfermedad de Chagas-Mazza.” La Prensa médica argentina 58 (1971): 869–872. Canguilhem, Georges. “Pathologie et physiologie de la thyroïde au XIXe siècle.” In Etudes d’histoire et de philosophie des sciences, 274–294. Paris, 1979. Carillo, Ramón. “Primera conferencia nacional de la enfermedad de Chagas (Buenos Aires, 1953).” In Jobino Pedro Sierra Iglesias, Salvador Mazza, su vida, su obra, redescubridor de la enfermedad de Chagas, 350–352. San Salvador de Jujuy, 1990. Carini, Antonio. “Contributo sperimentale alla etiologia del cretinismo.” Pathologica 5 (1912): 172a–b. ———. “Über Schizogony bei Trypanosomaen.” Archiv für Protistenkunde 24 (1911): 80–83. ———. “Ueber Trypanosoma minasense.” Archiv für Schiffs- und Tropenhygiene 13 (1909): 447–448. Carini, Antonio, and J. Maciel. “Comunicação sobre a moléstia de Chagas feita à Sociedade de Medicina e Cirurgia de São Paulo.” Arquivos da Sociedade de Medicina e Cirúrgica, São Paulo, 8, 9 (1913): 39–40. ———. “Distribution des triatomes dans l’Etat de São Paulo.” Bulletin de la Société de pathologie exotique 7 (1914): 292–295.

Delaporte-Bibliography.indd 156

6/27/2012 4:07:16 PM

Bibliography

157

———. “Existence de la maladie de Chagas dans l’Etat de São Paulo.” Bulletin de la Société de pathologie exotique 7 (1914): 289–292. Carneiro, Milton. História da Doença de Chagas. Curutiba, Brazil, 1963. Cerqueira, D. “Trypanosoma minasense.” Ciência médica 3 (1924): 155. Cerqueira Falcão, Edgard de. “Gaspar Vianna, sua vida e sua obra.” In Opera omnia de Gaspar Vianna, 9–39. Rio de Janeiro, 1962. Chagas, Carlos. “A forma cardíaca da tripanossomíase americana.” Arquivos brasileiros de medicina 18 (1928): 46–56. ———. American trypanosomiasis: Study of the Parasite and of the Transmitting Insect. Rio de Janeiro, 1920. ———. “Aspecto clínico geral da nova entidade mórbida produzida pelo Schizotrypanum cruzi.” Brasil-Médico (1910). In Coletânea de trabalhos cientificos, 87–89. Brasilia, 1981. ———. “Aspectos clínicos y anatomo patológicos de la Trypanosomiasis americana.” La Prensa médica argentina (1916). In Coletânea de trabalhos cientificos, 259–269. Brasilia, 1981. ———. “Aula Chagas, 21 Novembro 1914, 3° ponto (4a continuação).” Arquivos do Dr. Carlos Chagas. Fiocruz, document dactylographié. ———. Boletim da Academias nacional de medicina (Rio de Janeiro) (1922): 765–779. Session of December 14, 1922. ———. “Descoberta do Tripanosoma cruzi e verificação da Tripanosomíase Americana. Retrospecto Histórico.” Memórias do Instituto Oswaldo Cruz (1922). In Coletânea de trabalhos cientificos, 599–608. Brasilia, 1981. ———. “Die amerikanische Trypanosomiasis.” Handbuch der Inneren Medizin, 1367– 1381. Berlin, 1925; in Coletânea de trabalhos cientificos, 703–722. Brasilia, 1981. ———. “Discurso pronunciado pelo Dr. Carlos Chagas.” VII congresso brasileiro de medicina e cirurgia. Belo Horizonte, 1912. ———. Einige Ausdurcksformen der amerikanischen Trypanosomiasis (ChagasKrankheit). Rio de Janeiro, 1925. ———. “Epidemiologia da tripanossomíase Americana.” Brasil-Médico 32 (1918): 213b–214b. ———. “Estado atual da Tripanossomíase Americana.” Revista de biologia e higiene, 1934. In Coletânea de trabalhos cientificos, 759–767. Brasilia, 1981. ———. Estudos hematológicos do impaludismo. Rio de Janeiro, 1903. ———. “Forma cardíaca da Tripanossomíase Americana.” Memórias do Instituto Oswaldo Cruz 24 (1930): 89–125. ———. “Forma nervosa da tripanossomíase Americana.” Revista das clínicas (1930). In Coletânea de trabalhos cientificos, 755–758. Brasilia, 1981. ———. “Informações prestadas pelo Dr. Carlos Chagas à Academia de medicina.” Arquivos brasileiros de medicina 14 (1924): 69–88.

Delaporte-Bibliography.indd 157

6/27/2012 4:07:16 PM

158

Bibliography

———. Interview: “Como Chagas descobriu a moléstia que lhe imortalizou o nome.” A Noite, February 15, 1917. ———. “La trypanosomiase américaine: maladie de Chagas.” Annales des Laboratoires Clin (1926), 1–9. Reprint. ———. La Tripanossomiase américaine: Etude du parasite et de son insecte intermédiaire. Rio de Janeiro, 1923. ———. “Le cycle de Schizotrypanum cruzi chez l’homme et les animaux de laboratoire.” Bulletin de la Société de pathologie exotique 4 (1911): 467–471. ———. “Les formes nerveuses d’une nouvelle trypanosomiase.” Nouvelle Iconographie de la Salpêtrière (1913). Reprint. ———. Moléstia de Carlos Chagas ou tireoidite parasitária. Conference before the Associação médico cirúrgica de Minas Gerais, Rio de Janeiro, 1911. ———. Moléstia de Carlos Chagas ou tireoidite parasitária. Second lecture at the National Academy of Medicine. Rio de Janeiro, 1911. ———. “Neue Trypanosomen: Vorläufige Mitteilung.” Archiv für Schiffs- und Tropenhygiene 13 (1909): 120–122. ———. “Nouvelle espèce de trypanosomiase humaine.” Bulletin de la Société de pathologie exotique 6 (1909): 304–307. ———. “Nova entidade morbida do homem.” Brasil-Médico (1910). In Coletânea de trabalhos cientificos, 90–105. Brasilia, 1981. ———. “Nova entidade morbida do homem.” Memórias do Instituto Oswaldo Cruz (1911). In Coletânea de trabalhos cientificos, 109–155. Brasilia, 1981. ———. “Nova espécie morbida do homen, produzida por um tripanossoma (Trypanosoma cruzi),” nota prévia. Brasil-Médico 16 (1909): 227a–b. ———. “Nova tripanossomiase humana.” Imprenta Médica (São Paulo) 10 (1909): 154–155. ———. “Nova tripanossomíase humana.” Memórias do Instituto Oswaldo Cruz (1909). In Coletânea de trabalhos cientificos, 11–80. Brasilia, 1981. ———. Novas espécies de culicidios brasileiros. Rio de Janeiro, 1907. ———. “Novas estudos sobre a forma cardíaca da Tripanossomíase americana.” Memórias do Instituto Oswaldo Cruz 26 (1932): 329–338. ———. “O mal de Chagas.” Arquivos da Sociedade de medicina e cirurgia (1912). In Coletânea de trabalhos cientificos, 195–227. Brasilia, 1981. ———. “Oswaldo Cruz.” Memórias do Instituto Oswaldo Cruz (1916). In Oswaldo Cruz, no julgamento dos contemporâneos, 17–28. Rio de Janeiro, 1972. ———. “Processos patogénicos da tripanossomíase americana.” Memórias do Instituto Oswaldo Cruz (1916). In Coletânea de trabalhos cientificos, 387–417. Brasilia, 1981. ———. Profilaxia do impaludismo. 1906. In Coletânea de trabalhos científicos, 790–829. Brasilia, 1981.

Delaporte-Bibliography.indd 158

6/27/2012 4:07:16 PM

Bibliography

159

———. “Quelques aspects de la tripanossomiase américaine.” Revue d’hygiène 48 (1926): 694–702. ———. “Quelques aspects évolutifs du Trypanosoma cruzi dans l’insecte transmetteur.” Comptes rendus de la Société de biologie 97 (1927): 829–832. ———. Résumé de l’étiologie et des aspects cliniques de la trypanosomiase américaine. Rio de Janeiro, 1920. ———. “Revisão do ciclo evolutivo do Trypanosoma cruzi.” Brasil-Médico 23 (1913): 225a–b. ———. “Revision of the Life Cycle of Trypanosoma cruzi,” supplementary note. Brasil-Médico (1913). In Coletânea de trabalhos cientificos, 239–241. Brasilia, 1981. ———. “Sobre a etiologia do bocio endemico no Estado de Minas Gerais.” Brasil-Médico (1910). Reprint. ———. “Sobre um tripanossoma do tatu, Tatusia novemcincta, transmittido pela Triatoma geniculata Latr. (1811). Possibilidade de ser o tatu um depositário do Trypanosoma cruzi no mundo exterior.” Brasil-Médico (1912). In Coletânea de trabalhos cientificos, 228. Brasilia, 1981. ———. “Sur les altérations du coeur dans la trypanosomiasis américaine (maladie de Chagas).” Archives des maladies du coeur, des vaisseaux et du sang 21 (1928): 641–655. ———. “Trypanosoma minasense.” Brasil-Médico 48 (1908): 470a. ———. “A Trypanosome of the Armadillo, Tatusia novemcencta, Its Transmission by Triatoma geniculata and the Role of the Tatusia as an Out-of-Door Host of Trypanosoma cruzi.” Brasil-Médico (1912). Reprint. ———. “Trypanosomiase Americana: Uma rectifição do Dr Chagas a conferencia do Dr F. de Vasconcellos.” Jornal do comércio, August 23, 1919, 6a–7b. ———. “Trypanosomiasis Americana.” Revista española de medicina y cirurgia 11 (1928): 15a–18b. ———. “Trypanosomiasis Americana, forma aguda de la enfermedad” (Spanish translation and notes by Salvador Mazza). MEPRA 55 (1941): 3–45. ———. “Trypanossomíase Americana.” Revista do Brasil (1918). Reprint. ———. “Trypanossomíase americana: Forma aguda da moléstia,” Memorias do Instituto Oswaldo Cruz (1916). In Coletânea de trabalhos cientificos, 307–335. Brasilia, 1981. ———. “Über eine neue Trypanosomiasis des Menschen.” Archiv für Schiffsund Tropenhygiene (1909). In Coletânea de trabalhos cientificos, 5–7. Brasilia, 1981. ———. “Uma nova tripanossomiase humana.” Brasil-Médico 17 (1909): 175b–176b. Chagas, Carlos, and Carlos B. de Magarinos Torres. “Fecundação num flagelado de vida livre Prowazeckia cruzi, Hartmann et Chagas.” Brasil-Médico 29 (1916): 225a–b.

Delaporte-Bibliography.indd 159

6/27/2012 4:07:16 PM

160

Bibliography

Chagas, Carlos, and Henrique da Rocha Lima. “Amerikanische Trypanosomenkranheit: Chagas-Krankheit.” In Handbuch der Tropenkrankheiten, ed. Carl Mense, 5. Leipzig, 1929. In Coletânea de trabalhos cientificos, 643–692. Brasilia, 1981. Chagas, Carlos, and Eurico Villela. “Forma cardíaca da Tripanossomíase americana.” Memórias do Instituto Oswaldo Cruz, 1922. In Coletânea de trabalhos cientificos, 457–544. Brasilia, 1981. Chagas, Evandro. “Comentarios sobre la vida y la obra de Carlos Chagas.” Novena reunión de la Sociedad argentina de patología regional (Mendoza, Argentina) 103 (1935): 120–135. ———. “Forma cardíaca da Tripanossomíase Americana.” Memórias do Instituto Oswaldo Cruz 24 (1930): 89–125. ———. “Infection expérimentale de l’homme par le Trypanosoma cruzi.” Comptes rendus de la Société de biologie 115 (1933): 1339–1340. ———. “Infection expérimentale de l’homme par le Trypanosoma cruzi.” Comptes rendus de la Société de biologie 117 (1934): 390–392. ———. “Infection expérimentale par le Schizotrypanum cruzi chez l’homme.” Comptes rendus de la Société de biologie 118 (1935): 718. ———. “Novas estudos sobre a forma cardíaca da Tripanossomíase Americana.” Memórias do Instituto Oswaldo Cruz 26 (1932): 329–338. ———. “Súmula dos conhecimentos atuais sobre a Tripanossomíase americana.” Memórias do Instituto Oswaldo Cruz 30 (1935): 387–416. Chagas, Evandro, and Emmanuel Dias. “A propósito do sinal de Romaña.” O Hospital 19 (1941): 185–189. Chagas Filho, Carlos. “Carlos Chagas (1879–1934).” O Hospital 54 (1959): 9–25. ———. “Carlos Chagas e seus colaboradores.” O Estado de São Paulo, December 24, 1924, 27. ———. “Histórico sobre a doença de Chagas.” In Doença de Chagas, 5–21. Belo Horizonte, 1968. ———. Meu Pai. Rio de Janeiro, 1993. ———. “A Short Chronicle of the Discovery of the Chagas’ Disease.” Pace, Pacing and Clinical Electrophysiology 11 (1988): 1108. Chatton, Edouard, and R. Courrier. “Un Schizotrypanum chez les chauves-souris (Vesperugo pipistrellus) en Basse-Alsace: Schizotrypanose et goitre endémique.” Comptes rendus de la Société de biologie 84 (1921): 943–946. Chaves, Leocadio. “Carlos Chagas e o Instituto Oswaldo Cruz.” A Folha Médica 21 (1936): 308a–310b. ———. “Processos distróficos na moléstia de Carlos Chagas.” Memórias do Instituto Oswaldo Cruz 7 (1915): 200–213. Chirac, Auguste. L’exposition universelle de 1867. Illustrée. International Publication Authorized by the Imperial Commission. Paris, 1867.

Delaporte-Bibliography.indd 160

6/27/2012 4:07:16 PM

Bibliography

161

Clark, Herbert, and Laurence Dunn. “Experimental Studies on Chagas’ Disease in Panama.” American Journal of Tropical Medicine 12 (1932): 49–77. Coura, José Rodrigues. “Síntese histórica e evolucão dos conhecimentos sobre a doença de Chagas.” In Clínica e terapêutica da doença de Chagas, 469–486. Rio de Janeiro, 1977. Coursey, Elbert de. “The First Fatal Case of Chagas’ Disease Observed on the Isthmus of Panama.” American Journal of Tropical Medicine 15 (1935): 33–40. Crowell, Bowman. “The Acute Form of American Trypanosomiasis: Notes on Its Pathology, with Autopsy Report and Observations on Trypanosomiasis Cruzi in Animals.” American Journal of Tropical Medicine 3 (1923): 425–454. ———. “Trypanosoma Cruzi in the Tissues of the Armadillo.” Journal of the American Medical Association (1923). Reprint. Cruz, Bento. “Letter of December 19, 1922, to Professor Miguel Couto, president of the National Academy of Medicine.” A Folha Médica 25 (1923): 25c–26a. Cruz, Oswaldo. Opera Omnia. Rio de Janeiro, 1972. Cunha, A. M. da. “O Schizotrypanum cruzi e sua transmissão.” A Folha Médica 4 (1923): 17a–19c. Cunha, L. O ensino superior de Colônia à Era de Vargas: Educação e transformação. Rio de Janeiro, 1980. Damasceno, R. “Tripanosomideos de mamíferos da Região Amazônica.” Revista do Instituto de medicina tropical de São Paulo 3 (1961): 61–70. Darwin, Charles. Journal of Researches into the Geology and Natural History of the Various Countries visited by H.M.S Beagle, under the command of Captain Fitzroy, R. N., from 1832 to 1836. London, 1839. Deane, L. “Infecção natural do sagui Callithrix jacchus por tripanossoma de tipo cruzi.” Revista do Instituto de medicina tropical de São Paulo 4 (1962): 225–229. Deane, L., J. da Silva, and L. Lures Filho. “Nycthemeral variation in the parasitaemia of Trypanosoma minasense in naturally infected Marmosets of the genus Callithrix (Primates, Callithricidae).” Revista do Instituto de medicina tropical de São Paulo 16 (1974): 1–6. Delanoë, M. and Mme Pierre. “A propos du Schizotrypanom cruzi.” Bulletin de la Société de pathologie exotique 8 (1912): 599–602. ———. “De la rareté de Pneumocystis carinii chez les cobayes de la région de Paris. Absence de kystes chez d’autres animaux (lapin, grenouille, trois anguilles).” Bulletin de la Société de pathologie exotique 7 (1914): 271–272. ———. “Sur les rapports des kystes de Carini du poumon des rats avec le Trypanosoma lewisi.” Comptes rendus de l’Académie des sciences 7 (1912): 658–660. Delaporte, François. “Chagas, a lógica e a descoberta.” História, Ciências, Saúde, Manguinhos 1 (1995): 39–54.

Delaporte-Bibliography.indd 161

6/27/2012 4:07:17 PM

162

Bibliography

Dias, Emmanuel. “Estudos sobre o Schizotrypanum cruzi.” Memórias do Instituto Oswaldo Cruz 28 (1935): 1–111. ———. “Expériences sur la transmission du Trypanosoma cruzi de l’insecte au vertébré.” Comptes rendus de la Société de biologie 91 (1932): 490. ———. “Le Trypanosoma cruzi et ses rapports avec le système réticulo-endothélial.” Comptes rendus de la Société de biologie 110 (1932): 206–210. ———. “Le Trypanosoma cruzi pendant les première phases de l’infection expérimentale.” Comptes rendus de la Société de biologie 110 (1932): 203–205. ———. “Le xénodiagnostic appliqué à la tripanosomiase américaine.” Comptes rendus de la Société de biologie 118 (1935): 288–289. ———. O Barbeiro e a doença de Chagas. Rio de Janeiro, 1946. ———. “O ‘Signal de Romaña’ e os novos progressos no estudo da doença de Chagas.” A Folha Médica 17 (1936): 345b–347b. ———. “O signal de Romaña e sua influencia na evolução dos conhecimentos sobre moléstia de Chagas.” Brasil-Médico 42 (1939): 965a–970a. ———. “O ‘Signal de Romaña’ na moléstia de Chagas.” Acta médica 3 (1939): 1–2. ———. “Persistance de l’infection par le Schizotrypanum cruzi chez l’hommem.” Comptes rendus de la Société de biologie 117 (1932): 506–507. ———. “Xenodiagnostico e algunas verificacções epidemiologicas na moléstia de Chagas.” Novena reunión de la Sociedad argentina de patología regional (Buenos Aires) (1935). Dias, Ezequiel. “Dr Oswaldo Gonçalvez Cruz (1872–1917).” Bulletin of the International Association of Medical Museums and Journal of Technical Methods (1922). Reprint. ———. “Moléstia de Carlos Chagas. Estudos hematológicos.” Memórias do Instituto Oswaldo Cruz 4 (1912): 34–60. ———. O Instituto Oswaldo Cruz: Esboço histórico (1899–1916). Rio de Janeiro, 1918. ———. “Traços de Oswaldo Cruz.” Memórias do Instituto Oswaldo Cruz 15 (1922): 5–68. Dios, R., J. Zuccarini, and J. Oyarzabal. “Sobre un nuevo caso de tripanosomiasis humana en la Republica Argentina.” Revista de la Sociedad argentina de biologia 2 (1925): 335–337. Donat, Fae. “Experimental Studies on Trypanosoma cruzi in California.” Proceedings of the Society for Experimental Biology and Medicine 32 (1934): 61–62. Dujarric de la Rivière, René. “Carlos Chagas (1879–1934).” Revue médicale française 16 (1935): 95. Elmassian M. “Mal de Caderas: Flagelosis paresiante de los Equideos.” Revista de la Sociedad médica argentina 10 (1902): 122–148. Escomel, Edmundo. “La trypanossomíase humaine existe dans les forêts orientales du Pérou.” Bulletin de la Société de pathologie exotique 12 (1919): 723–726.

Delaporte-Bibliography.indd 162

6/27/2012 4:07:17 PM

Bibliography

163

Fernandes, Tânia Maria. “Oswaldo Cruz X Barão de Pedro Affonso: Polêmica no controle de imunizantes.” Cadernos da Casa de Oswaldo Cruz 1 (1989): 32–43. Ferreira, M. “Homenagem.” Boletim de higiene e saúde pública 4 (1946): 13–18. Ferri, Mario Guimarães, and Shozo Motoyama. História das Ciências no Brasil. São Paulo, 1979–80. Fodéré, François. Traité du goitre et du crétinisme. Paris, 1799. Fonseca Filho, Olympio da. A Escola de Manguinhos: Contribução para o estudo do desenvolvimiento da medicina experimental no Brasil. Separata do tomo II de Oswaldo Cruz: “Monumenta Histórica.” São Paulo, 1974. ———. “Arthur Neiva.” Anais da Academia Brasileira de Ciências 16 (1944): 153–162. ———. “Carlos Chagas e a descoberta da Trypanosoma americana.” Medicina Brasileira, 1940, 112. ———. “O parasito da doença de Chagas.” Anais do Congresso internacional sobre a doença de Chagas (1972): 513–524. Reprint. ———. “Oswaldo Cruz e sua escola de medicina experimental em Manguinhos.” Ciência e Cultura 24 (1972): 507–510. ———. “Uma carta do Dr. Olympio da Fonseca Filho sobre a comunicação de Parreiras Horta.” O Globo, November 26, 1923. Foster, William. A History of Parasitology. Edinburgh, 1965. Fraga, Clementino. “Nova entidade mórbida do homem descoberta e estudada pelo Dr. Carlos Chagas.” Gazeta médica da Bahia 47 (1911): 198–220. ———. Vida e obra de Oswaldo Cruz. Rio de Janeiro, 1972. França, Carlos. “Breve história da parasitologia.” In Quatro lições de parasitologia, 3–31. Lisbon, 1925. Freire, Gilberto. Casa grande e Senzal. 16th ed. Rio de Janeiro, 1973. Quoted in Luiz Antônio Cunha, O ensino superior da Colônia à Era de Vargas: Educação e transformação. Rio de Janeiro, 1980. Gaillard, Henri. “Remarque sur la culture de Trypanosoma cruzi Chagas.” Annales de parasitologie humaine et comparée 7 (1929): 367–376. Gaminara, Angel. “Estudio experimental sobre Schizotrypanum Cruzi y enfermedad de Chagas en el Uruguay.” Anales de la Facultad de medicina 8 (1923): 311–359. ———. “Infeccion natural de Triatoma Rubrovaria por Schizotrypanum cruzi en el Uruguay.” Boletin del consejo nacional de hygiene 17 (1923): 571–574. Geoghegan, Arnoldo. “A propos d’un nouveau cas de trypanosomiase humaine américaine dans la ville de Catamarca.” Comptes rendus de la Société de biologie 100 (1929): 137. ———. “Deux nouveaux cas de trypanosomiase américaine humaine dans la province de Catamarca. Comptes rendus de la Société de biologie 99 (1928): 1417–1418. Gomes, J. ”Triatomas e moléstia de Chagas no Estado de São Paulo.” Memórias do Instituto de Butantan, 1916, 403–411.

Delaporte-Bibliography.indd 163

6/27/2012 4:07:17 PM

164

Bibliography

Gonçalves, A. Moléstia de Chagas na Bahia (Tese Inaugural). Bahia, 1912. Grasset E. “L’hématozoaire du goitre.” Comptes rendus de l’Académie des sciences 127 (1898): 75–77. Gruby, David. “Recherches et observations sur une nouvelle espèce d’hématozoaire, Trypanosoma sanguinis.” Comptes rendus de l’Académie des sciences 17 (1843): 1134–1136. Guerra, Egídio de Sales. Oswaldo Cruz. Rio de Janeiro, 1940. Guerra, Francisco. “American Trypanosomiasis: An Historical and a Human Lesson.” Journal of Tropical Medicine and Hygiene 73 (April–May 1970): 83–118. Reprint, 1–36. Gull, William. “On a Cretinoid State Supervening in Adult Life in Woman.” Transactions of the Clinical Society of London 7 (1873–74): 180–185. Gumilla, Joseph. El Orinoco Ilustrado: Historia natural, civil y geografica de este gran rio (Madrid, 1741), 426. In Francisco Guerra, “American Trypanosomiasis: An Historical and a Human Lesson.” Journal of Tropical Medicine and Hygiene 73 (April–May 1970): 83–118. Reprint, 1–36. Harant, Hervé. Histoire de la parasitologie. Palais de la découverte. Paris, 1955. Hartmann, Max. “Das System der Protozoen.” Archiv für Protistenkunde 10 (1909): 139–160. ———. “Notiz über eine weitere Art der Schizogonie bei Schizotrypanum cruzi (Chagas).” Archiv für Protistenkunde 20 (1910): 361–363. Hartmann, Max, and V. Jollos. “Die Flagellaten-Ordnung Binucleata.” Archiv für Protistenkunde 19 (1910): 8–80. Herr, A., and Lucien Brumpt. “Un cas aigu de maladie de Chagas contractée accidentellement au contact de triatomes mexicains: Observation et courbe fébrile.” Bulletin de la Société de pathologie exotique 32 (1939): 565–571. Hoare, Cecil. Handbook of Medical Protozoology. London, 1949. ———. “The Transmission of Chagas’ Disease: A Critical Review.” Tropical Diseases Bulletin 31 (1934): 757–762. ———. The Trypanosomes of Mammals. London, 1972. Hoare, Cecil, and F. Coutelen. “Essai de classification des trypanosomes des mammifères et de l’homme basée sur leurs caractères morphologiques et biologiques.” Annales de parasitologie 11 (1933): 196–200. Instituto de Manguinhos. Institut für Experimentelle Pathologie in Rio de Janeiro. Berlin, 1907. Instituto Oswaldo Cruz. Rio de Janeiro, 1948. Instituto Oswaldo Cruz em Manguinhos. Rio de Janeiro, 1909. Instituto Oswaldo Cruz Manguinhos Rio de Janeiro. Internationale HygieneAusstellung, Dresden, 1911. Ivern, Andrés. Vida y obra de Salvador Mazza. Rosario, 1987.

Delaporte-Bibliography.indd 164

6/27/2012 4:07:17 PM

Bibliography

165

Jeandelize, Paul. Insuffisance thyroïdienne et parathyroïdienne. Paris, 1904. Jörg, Miguel. Tripanossommiasis cruzi Humana o Enfermedad de Chagas-Mazza. Buenos Aires, 1974. Kean, Benjamin Harrison. “Carlos Chagas and Chagas’ Disease.” American Journal of Tropical Medicine and Hygiene 26 (1977): 1084a–1087b. Kleine, Friedrich. “Positive Infektionsversuch mit Trypanosoma brucei durch Glossina palpalis.” Deutsche Medizinische Wochenschrift 35 (1909): 469–470. ———. “Weitere wissenschaftliche Beobachtungen über die Entwicklung von Trypanosomen in Glossinen.” Deutsche Medizinische Wochenschrift 29 (1909): 1257–1260. Koberlé, Eugène. “Essai sur le crétinisme.” In Traité des maladies mentales, ed. E. Dagonet. Strasbourg, 1862. Koch, Robert. “Bericht über die Tätigkeit der deutschen Expedition zur Erforschung der Schlafkrankheit bis zum 25 November, 1906.” Deutsche Medizinische Wochenschrift 2 (1907): 49–51 ———. “Ueber den bisherigen Verlauf der deutschen Expedition zur Erforschung der Schlafkrankheit in Ostafrika.” Deutsche Medizinische Wochenschrift 51 (1906): 1–8. ———. “Ueber die Unterscheidung der Trypanosomenarten.” Sitzungsberichte der königlich-preussischen Akademie der Wissenschatften zu Berlin 96 (1905): 958–962. ———. “Vorläufige Mitteilungen über die Ergebnisse einer Forschungsreise nach Ostafrica.” Deutsche Medizinische Wochenschrift 31 (1905): 1865–1869. Kocher, Emil. “Über Kropfexstirpation und ihre Folgen.” Archiv für klinische Chirurgie 29 (1883): 254–337. Kofoid, Charles, and Irène McCulloch. “On Trypanosoma triatomae, a New Flagellate from Hemipteron Bug from the Nests of the Wood Rat Neatoma fuscipes.” University of California Publications in Zoology 16 (1916): 113–124. Kofoid, Charles, and Fae Donat. “Experimental Infection with Trypanosoma cruzi from Intestine of Cone-nose bug, Triatoma protracta.” Proceedings of the Society for Experimental Biology and Medicine 30 (1933): 489–491. ———. “South American Trypanosomiasis of the Human Type-occurrence in Mammals in the United States.” California and Western Medicine 38 (1933): 245a–248b. Kraus, Rudolph. “Die chagaskrankheit, Kropf und Kretinismus in Südamerika.” Wiener Klinische Wochenschrift 39 (1925): 378–382. ———. “El problema de la etiología y patogenía del bocio endemic y del cretinismo.” Revista del Instituto bacteriológico 2 (1919): 309–323. Kraus, Rudolph, Carlos Maggio, and Francisco Rosenbusch. “Bocio, cretinismo y enfermedad de Chagas (Primera comunicación).” La Prensa médica argentina 1 (1915): 2a–5b.

Delaporte-Bibliography.indd 165

6/27/2012 4:07:17 PM

166

Bibliography

Kraus, Rudolph, and Francisco Rosenbusch. “Bocio, cretismo y enfermedad de Chagas (Segunda comunicación).” La Prensa médica argentina 17 (1916): 177b–180a. Lacorte, J. “A reacção do desvio do complemento na Moléstia de Chagas.” Memórias do Instituto Oswaldo Cruz 20 (1927): 197–224. Lacôrte, José G. “Oswaldo Cruz, sua atuação no campo da pesquisa científica e da saúde pública.” Atas da Sociedade de biologia de Rio de Janeiro 15 (1972): 113–119. Lage, Guillermo. “La Trypanosomiasis americana. Conmemoracion del primer cincuentenario del descubrimiento de Carlos Chagas.” Revista de la Sociedad cubana de Historia de medicina 2 (1959): 44–57. Lanfranchi, A. “Sul possible passaggio de tripanosimi nel latte, 2e note.” Atti Accademia Lincei Rendiconti 25 (1916): 369. Laveran, Alphonse, and Felix Mesnil. Trypanosomes et Trypanosomiases. 2nd ed. Paris, 1912. Leboeuf, M. “Etude clinique sur la tripanosomiase humaine (maladie du sommeil).” Annales d’hygiène et de médecine coloniales 11 (1908): 381–393. Leonard, John. “Carlos Chagas, Pionero de la salud en el interior del Brasil.” Boletin de la Oficina Sanitaria Panamericana 110 (1991): 185a–198b. Lessa, G. “A epidemiologia da moléstia de Chagas.” Boletim sanitário 3 (1923): 3–27. Lewinsohn, Rachel. “Carlos Chagas (1879–1934): The Discovery of Trypansoma cruzi and of American Trypanosomiasis.” Transactions of the Royal Society of Tropical Medicine and Hygiene 73 (1979): 513a–523b. ———. “Carlos Chagas and the Discovery of Chagas’s Disease (American Trypanosomiasis).” Journal of the Royal Society of Medicine 74 (1981): 451–455. Lignières, José. “Contribution à l’étude de la trypanosomose des équidés sudaméricains connue sous le nom de mal de caderas.” Revista de la Sociedad médica argentina 10 (1902): 482–488. Lizarraga, Reginaldo de Ovando. Descripcion breve de toda la Tierra del Peru, Tucaman, Rio de la Plata y Chile. In Historiadores de Indias, Obras Completas, 2:544-645. Madrid, 1909. Lobo Leite, A. “Doença de Chagas e bócio endêmico.” Brasil-Médico 46 (1939): 1031a–1033a. Lozano, Nicolas. “La enfermedad de Chagas.” Archivo de higiene 4 (1911): 125–176. Lutz, Adolfo, H. da Souza Araujo, and Olympio da Fonseca Filho. “Viagem Científica no Rio Paraná e a Assunção com volta por Buenos Aires, Montevidéu e Rio Grande.” Memórias do Instituto Oswaldo Cruz 10 (1918): 120–159. Magalhães, Octavio de. “A Volta de Carlos Chagas.” São Paulo Médico 65 (1944): 133–159.

Delaporte-Bibliography.indd 166

6/27/2012 4:07:17 PM

Bibliography

167

———.“Chagas e a Saúde Pública.” A Folha Médica 21 (1936): 305a–306b. ———. “Um poco da vida de Carlos Chagas.” Memória do Instituto Biológico Ezequiel Dias 4 (1942): 3–16. Maggio, Carlos, and Francisco Rosenbusch. “Estudio de los Trypanosomas de las Vinchucas de la República Argentina.” Anales del Departamento nacional de higiene 21 (1914): 220–228. Marchoux, Emile. “Carlos Chagas.” La Presse médicale 1 (1935): 1–18. ———. “Carlos Chagas.” A Folha Médica 21 (1936): 313a–314b. ———. “Notice nécrologique sur Carlos Chagas.” Bulletin de l’Académie de médecine (1934). Reprint. Martin, G. “Trypanosomiase américaine.” In Traité de pathologie exotique, ed. Charles Grall and Albert Clarac, 3:394–399. Paris, 1912. Martinetti, C. “Investigaciones sobre la existencia de la enfermedad de Chagas, en la zona del ferrocaril a la Costa.” Boletín de medicina y cirurgía 32 (1929): 26–44. Matta, A. “Un nouveau réduvide de l’Amazone, Rhodnius Brethesi n. sp.” Bulletin de la Société de pathologie exotique 12 (1919): 611–612. Mayer, Martin. “Über den Dauerparasitismus von Schizotrypanum cruzi bei Ornithodorus moubata.” Archiv für Schiffs- und Tropenhygiene 22 (1918): 158–160. Mayer, Martin, and Henrique da Rocha Lima. “Zur Entwicklung von Schizotrypanum cruzi in Säugetieren.” Archiv für Schiffs- und Tropenhygiene 16 (1912): 90–94. ———. “Zum Verhalten von Schizotrypanum cruzi in Warmblütern und Arthropoden.” Archiv für Schiffs- und Tropenhygiene 18 (1914): 101–136. Mazza, Salvador. “Caso de esquizotrypanosis humana observado en la ciudad de Jujuy (nota preliminar).” Revista de la Sociedad argentina de biología 1 (1925): 79–86. ———. “Enfermedad de Chagas en San Juan, consideraciones generales.” MEPRA 43 (1940): 20–25. ———. “Inexistencia de un síntomas patognomonico en forma agudas de Enfermedad de Chagas.” Le Prensa médica argentina (1939). Reprint. ———. “Nota sobre le primer centenar de formas agudas de enfermedad de Chagas comprobadas en la República por la Misión de estudios de pathología regional argentina.” Le Prensa médica argentina (1936). Reprint. ———. “Sobre el valor del edema palpebral de un solo lado para el diagnostico de forma aguda de la Enfermedad de Chagas.” Novena reunión de la Sociedad argentina de patología regional (Buenos Aires) 110 (1935): 343–354. Mazza, Salvador, and C. Benítez. “Comprobación de la naturaleza esquizotripanosoica y frecuencia de la dacrioadenitis en la enfermedad de Chagas.” MEPRA 31 (1937): 3–31. Mazza, Salvador, and Miguel Jörg. “Consideraciones sobre la patogenia de la enfermedad de Chagas.” Novena reunión de la Sociedad argentina de patología regional (Buenos Aires) 45 (1935): 221–231.

Delaporte-Bibliography.indd 167

6/27/2012 4:07:17 PM

168

Bibliography

Mazza, Salvador, S. Miyara, Germinal Basso, and Redento Basso. Primer Quinquenión de la investigación por la MEPRA de la enfermedad de Chagas en la Provincia de Mendoza. Mendoza, 1941. Mazza, Salvador, and C. Nastri de Fischer. “Primeras comprobaciones de casos de enfermedad de Chagas en San Juan.” MEPRA 25 (1935): 12–18. Mazza, Salvador, and Cecilio Romaña.“Infeccion espontanea de la comadreja del chaco Santafecino por Trypanosoma cruzi.” Septima reunión de la Sociedad argentina de patología regional del Norte (Buenos Aires) (1932): 981–989. ———. “Nuevas observaciones sobre la infección espontánea de armadillos del país por el Trypanosoma cruzi.” La Prensa médica argentina (1931). Reprint. ———. “Otro caso de forma aguda de enfermedad de Chagas en el norte santafecino.” MEPRA 15 (1934): 25–54. Mazza, Salvador, Cecilio Romaña, and B. Parma. “Caso agudo de enfermedad de Chagas con lesion cutanea de inoculacion.” MEPRA 28 (1936): 29–33. ———. “Un nuevo caso mortal de enfermedad de Chagas observado en el norte santafecino.” MEPRA 21 (1935): 3–18. Mazza, Salvador, Cecilio Romaña, and K. Schürmann. “Nuevas observaciones sobre la infección espontánea de armadillos del país por el Trypanosoma cruzi.” La Prensa médica argentina (1931). Reprint. Mazza, Salvador, Cecilio Romaña, and Emilio Zembra. “Comprobación de lésion cutanea de inoculacion en un caso de nefermedad de Chagas.” La Prensa médica argentina 28 (1936): 34–40. Mazza, Salvador, and A. Ruchelli. “Comprobación de dos casos agudos de enfermedad de Chagas en Tinogasta (Catamarca).” La Prensa médica argentina 20 (1934): 3–19. McCarrison, Robert. “Further Observations on Endemic Goitre.” Lancet 1 (1906): 1110. ———. “Further Researches on the Etiology of Endemic Goitre.” Quarterly Journal of Medicine 2 (1908–1909): 285–287. ———. “The Milroy Lectures on the Etiology of the Endemic Goitre.” Lancet 1, Lectures 1, 2 (1913): 147a–226b; Lecture 3 (1913): 365a–373b. ———. “Observations on Endemic Goitre in the Chitral and Gilgit Valley.” MedicoChirurgical Transactions 139 (1906): 437. Medvei, Victor Cornelius. A History of Endocrinology. Lancaster, 1982. Meyer, C. Relatório de 1914 do diretor do Instituto bacteriológico de São Paulo. São Paulo, 1915. Migone, Luis. “Le rôle des carpinchos comme réservoirs de virus dans la conservation du mal de caderas.” Bulletin de la Société de pathologie exotique 3 (1910): 525–530. Miles, M. A., and Jean Rouse. Chagas’s Disease (South American trypanosomiasis): A Bibliography Compiled from “Sleeping Sickness Bureau Bulletin,” 1908–12, and

Delaporte-Bibliography.indd 168

6/27/2012 4:07:17 PM

Bibliography

169

“Tropical Diseases Bulletin,” 1912–1970. London: Bureau of Hygiene and Tropical Diseases, 1970. Miller, J. “Chagas’ Disease in Panama, Report of Three Cases.” Southern Medical Journal 24 (1931): 645–647. Minchin, E. “Investigations on the Development of Trypanosomes in Tsetse-Flies and Others Diptera.” Quarterly Journal of Microscopical Science 52 (1908): 159–252. Minchin, E., and J. Thomson. “On the Occurrence of an Intracellular Stage in the Development of Trypanosoma lewisi in the Rat-Flea.” British Medical Journal 2 (1911): 361a–364a. ———. “Transmission of T. lewisi by the Rat-Flea (Ceratophyllus fasciatus).” British Medical Journal 2 (1911): 1309–1310. ———. “The Transmission of Trypanosoma lewisi by the Rat-Flea (Ceratophyllus fasciatus).” Proceedings of the Royal Society 82 (1910): 273–285. Minoprio, J. L. “Consideraciones sobre los trabajos originarios del Dr Carlos Chagas.” Boletín de la Academia nacional de medicina 57 (1979): 333–344. Mülhens, P., R. Dios, J. Petrocchi, and J. Zuccarini. “Tripanosomiasis humana.” Revista del Instituto bacteriologico 4 (1925): 290–323. Muniz, Julio. “Quelques formes intéressantes trouvées dans des cultures de Trypanosoma cruzi.” Comptes rendus de la Société de biologie 97 (1927): 821–823. Munk, F. “Die Chagaskrankheit: Bericht über eine Expedition in Brasilien.” Medizinische Klinik 19 (1923): 784–788. Nattan-Larrier, Louis. “Hérédité des infections expérimentales à Schizotrypanum cruzi.” Bulletin de la Société de pathologie exotique 14 (1921): 232–238. ———. “La schizotrypanosomiase américaine peut-elle être transmise par contagion génitale?” Comptes rendus de la Société de biologie 84 (1921): 773–775. ———. “Sur le passage des trypanosomes dans le lait.” Revue de pathologie comparée 98 (1913): 282–286. Neiva, Arthur. “Contribuição para o conhecimento dos hemípteros hematófagos da América central.” Brasil-Médico (1915). In Triatomídeos Coletânea, 4:105–108. Rio de Janeiro, 1944. ———. “Da transmissão do Trypanosoma cruzi pela Triatoma sordida Stal.” BrasilMédico (1913). In Triatomideos Coletânea, 4:37. Rio de Janeiro, 1944. ———. “Informações sobre a biologia do Conorhinus megistus Burm.” Memórias do Instituto Oswaldo Cruz (1910). In Triatomideos Coletânea, 4:1–6. Rio de Janeiro, 1944. ———. “Oswaldo Cruz.” Anais paulistas de medicina e cirurgia 8 (1917): 29–35. ———. “Penetração do Trypanosoma evansi a través da conjuntiva da cobaia (nota prévia).” Brasil-Médico (1913). Reprint. ———. “Presença em uma localidade do Estado do Rio de um novo transmissor da ‘Moléstia de Chagas’ encontrado infectado em condições naturais.” Brasil-Médico (1914). In Triatomideos Coletânea, 4:99–104. Rio de Janeiro, 1944.

Delaporte-Bibliography.indd 169

6/27/2012 4:07:17 PM

170

Bibliography

———. “Revisão do gênero Triatoma Lap.” Thesis, 1914. In Triatomideos Coletânea, 4:53–98. Rio de Janeiro, 1944. Neiva, Arthur, and Belisário Penna. “Viagem científica pelo norte da Bahia, sudoeste de Pernambuco, sul de Piauí e do norte ao sul de Goiaz.” Memórias do Instituto Oswaldo Cruz (1916). In Triatomideos Coletânea, 4:109–27. Rio de Janeiro, 1944. Niño, Flavio. “A propósito de un nuevo caso de enfermedad de Chagas en la República Argentina.” Cuarta reunión de la Sociedad argentina de patología regional del Norte (Buenos Aires) (1928): 579–585. ———. Contribución al estudio de la enfermedad de Chagas o trypanosomiasis americana. Buenos Aires, 1929. Noguchi, Hydeo. Proceeding of the International Conference on Health Problems, 553. Boston, 1924. Nöller, W. “Die Uebertragungsweise der Rattentrypanosomen. II.” Archiv für Protistenkunde 34 (1914): 293–335. Normand A. L’architecture des nations étrangères. Paris, 1870. Novaes, Eucario. “La trypanossomiase brésilienne et son rapport avec le corps thyroïde.” Revue médicale de la Suisse romande 36 (1916): 593–614. Nutall, George. “The Transmission of Trypanosoma lewisi by Fleas and Lice.” Parasitology 1 (1909): 296–301. Oliveira, G. de. “Isolamento de Trypanosoma lewisi e outras noções concernentes à Moléstia de Chagas no Rio Grande do sul (nota prévia).” Brasil-Médico 34 (1920): 142a–143b. Oliveira, Octavio G. de. Oswaldo Cruz e suas atividades na direcção da Saúde Pública Brasileira. Rio de Janeiro, 1955. Olle, Rodolfo. “Syntomas oculares de la enfermedad de Chagas y su significación diagnóstica.” MEPRA 20 (1937): 30–49. Ord, William. “On Myxoedema, a Term Proposed to Apply to an Essential Condition in the Cretinoid Affection Occasionally Observed in Middle-Aged Women.” Medical and Chirurgical Transactions 67 (1878): 57–58. Parreiras Horta, Paulo. Boletim da Academia nacional de medicina (Rio de Janeiro) (1923): 693–726. Session of November 22, 1923. Pasteur, Louis. “Lettre de Pasteur à l’empereur du Brésil,” September 22, 1884. In Daniel Raichvarg, Éthique médicale et Droits de l’homme, 164–165. Paris, 1988. Pasteur Vallery-Radot, Louis. Un aspect inconnu du Brésil, l’oeuvre de Carlos Chagas. Palais de la découverte. Paris, 1955. Patton, W. “A Critical Review of Our Present Knowledge of the Hemoflagellates and Allied Forms.” Parasitology 2 (1909): 91–139. Patton, W., and C. Strickland. “A Critical Review of the Relation of Blood-Sucking Invertebrates to the Life Cycles of the Trypanosomes of Vertebrates, with a Note

Delaporte-Bibliography.indd 170

6/27/2012 4:07:17 PM

Bibliography

171

on the Occurrence of a Species of Crithida, C. Ctenopthalmus, in the Alimentary Tract of Ctenopthalmus agyrtes, Heller.” Parasitology 1 (1908): 322–346. Peixoto, Afrânio. Boletim da Academia de medicina (1922): 723d. In L. Ribeiro, Afrânio Peixoto, 190–191. Rio de Janeiro, 1950. Penna, Belisário. Saneamento do Brasil. Rio de Janeiro, 1918. Penna de Azevedo, Arthur. “Histologia patológica da glândula tireóide na forma aguda da Moléstia de Chagas.” Memórias do Instituto Oswaldo Cruz 27 (1933): 93–123. Perleth, Matthias. “The Discovery of Chagas’ Disease and the Formation of the Early Chagas’ Disease Concept.” History and Philosophy of the Life Sciences 19 (1997): 211–236. ———. Historical Aspects of American Trypanosomiasis (Chagas’ Disease). Frankfurt am Main, 1977. Peryassu, Antônio. “Homenagem.” Boletim de hygiene e saúde pública 4 (1946): 8–12. ———. “Os Hemípteros hematófagos, nocivos ao homem, encontrados no Brasil: Sua biologia e seu papel como vetores de doenças.” A Folha Médica 8 (1921): 17a–22c. Pick, F. “Sur le ‘Signe de Romaña.’ ” Acta tropica 11 (1954): 105–137. Piraja da Silva, Manuel. “Notas de parasitologia. O barbeiro (Conorhinus megistus Burm.) na Bahia.” Arquivos brasileiros de medicina 3 (1911): 627–632. Prado, A. de. “Meio século de existência clínica da “Doença de Chagas.” Revista do Instituto medicina tropical São Paulo 1 (1959): 219–228. Prowazeck, Stanislaus von. Handbuch der Pathogenen Protozoen. Leipzig, 1912. ———. “Kritische Bemerkungen zum Trypanosomenproblem.” Archiv für Schiffsund Tropenhygiene 13 (1909): 301. ———. Physiologie der Einzellingen. Leipzig, 1909. ———. “Studien über Säugethier Trypanosomen.” Arbeiten aus dem kaiserlichen Gesundheitsamte 22 (1905): 351–395. Ramos, J. “Moléstia de Chagas.” O Hospital 58 (1960): 417–419. Reichenow, E. “Beiträge zur Kenntnis der Chagaskrankheit.” Archiv für Schiffs- und Tropen-hygiene 38 (1934): 459–477, 499–518. Reidel, G. “Glândula tiróide e sua secreção interna.” Arquivos brasileiros de medicina 4 (1911): 799–842. Reis, José. “Recordações do Instituto Oswaldo Cruz.” Ciência e Cultura 31 (1979): 19. Reverdin, Jacques. “Contribution à l’étude du myxœdème consécutif à l’extirpation totale ou partielle du corps thyroïde.” Revue médicale de la Suisse romande 7 (1887): 275–291, 318–330. Ribiero, L. Afrânio Peixoto. Rio de Janeiro, 1950. ———. Medicina no Brasil Colonial. Rio de Janeiro, 1971.

Delaporte-Bibliography.indd 171

6/27/2012 4:07:17 PM

172

Bibliography

Rocha Lima, Henrique da. “Com Oswaldo Cruz em Manguinhos.” Ciência e Cultura 4 (1952): 15–38. Rodhain, Jean. “Notes sur Trypanosoma minasense Chagas.” Comptes rendus de la Société de biologie 125 (1937): 1025–1034. ———. “Notes sur Trypanosoma minasense Chagas: Evolution du trypanosome du Saimiri chez divers arthropodes.” Comptes rendus de la Société de biologie 126 (1937): 69–72. ———. “Notes sur Trypanosoma minasense Chagas: Identité spécifique du trypanosome du Saimiri Chrysothrix sciureus.” Acta biologica belga 1 (1941): 187–192. Romaña, Cecilio. “Acerca de un síntoma inicial de valor para el diagnostico de forma aguda de la enfermedad de Chagas: La conjuntivitis esquizotrypanosica unilateral.” MEPRA 22 (1935): 16–28. ———. “Comprobación de formas agudas de tripanosomiasis americana en el Chaco austral y santafecino.” MEPRA 14 (1934): 3–24. ———. “Comprobación de formas crónicas cardiacas de la Trypanosomiasis americana en el norte santafecino.” MEPRA 14 (1934): 25–45. ———. “Dos casos agudos más de enfermedad de Chagas en el norte santafecino.” MEPRA 21 (1935): 19–32. ———. “Le parasitisme des cellules épithéliales de la conjonctivite du singe.” Bulletin de la Société de pathologie exotique 32 (1939): 810–813. ———. “Novas investigações sobre a moléstia de Chagas na República Argentina.” Revista médico-cirúrgica do Brasil 1–10 (1934): 298–307. ———. “Nuevas comprobaciones de formas agudas puras de enfermedad de Chagas en el norte santafecino.” MEPRA 20 (1934): 19–31. ———. “Otro caso de forma aguda de enfermedad de Chagas observado en el norte santafecino.” MEPRA 15 (1934): 25–54. ———. Réplica. Tucamán, Argentina, 1944. ———. “Reproduction chez le singe de la ‘conjonctivite schizotrypanosomienne unilatérale.’ ” Bulletin de la Société de pathologie exotique 32 (1939): 390–394. ———. “Trypanosomiasis americana y bocio endémico.” La Semana médica 42 (1935): 897b–902b. Romaña, Cecilio, and K. Schürmann. “La infeccion espontanea y la experimental del tatu del Chaco santafecino por el Trypanosoma cruzi.” Septima reunión de la Sociedad argentina de pathologia regional del Norte (Buenos Aires) (1932): 969–979. Rosenbusch, Francisco. “Comisión de investigación sobre bocio, cretinismo y enfermedad de Chagas en la provincial de Salta.” Anales del Departamento nacional de higiene 23 (1916): 117–127. ———. “Comisiones cientificas de estudioa bacteriológicos y entomológicos en las provincias.” Anales del Departamento nacional de higiene 23 (1916): 132–134.

Delaporte-Bibliography.indd 172

6/27/2012 4:07:17 PM

Bibliography

173

Roubaud, Emile. “Infection naturelle de la trompe des glossines.” Bulletin de la Société de pathologie exotique 105 (1908): 564–568. ———. “Fixation, multiplication, culture d’attente des trypanosomes pathogènes dans la trompe des mouches tsé-tsé.” Comptes rendus de l’Académie des sciences 146 (1908): 423. ———. “Transmission de Trypanosoma dimorphon par Glossina palpalis, R. Desd.” Annales de l’Institut Pasteur 21 (1907): 466–467. Salvin-Moore, J., and Anton Breinl. “The Cytology of the Trypanosomes. Part I.” Annals of Tropical Medicine and Parasitology 1 (1908): 441–490. Salvin-Moore, J., and Edward Hindle. “The Life History of Trypanosomas lewisi.” Annals of Tropical Medicine and Parasitology 2 (1908): 197–212. Schaudinn, Fritz. “Generations- und Wierthswechsel bei Trypanosoma und Spirochaeta (Vorläufigre Mittheilung).” Arbeiten aus dem kaiserlichen Gesundheitsamte 20 (1904): 387–439. Scott, Sir Henry Harold. A History of Tropical Medicine. Vol. 1. London, 1939. Segovia, Juan C. “Estudio sobre trypanosomiasis.” Arquivos paranaenses de medicina 11 (1915): 65–67. ———. Trypanosomiasis en el Salvador. Trabajo presentado al sexto Congreso médico latino-americano, reunido en la Habana en Noviembre de 1922, 1–19. San Salvador, 1922. ———. “Un caso de Trypanosomiasis.” Archivo del Hopital Rosales 10 (1913): 249–254. ———. “Une nouvelle tripanossomiase observée au Salvador.” Revue de médecine et d’hygiène tropicales 9 (1914): 111–117. Sergent, Edmond, and Etienne Sergent. “Hémamibes des oiseaux et moustiques. ‘Générations alternantes’ de Schaudinn.” Comptes rendus hebdomadaires des séances et Mémoires de la Société de biologie 1 (1905): 57–59. ———. “Sur le second hôte de l’Haemoproteus (Halteridium) du pigeon (note préliminaire).” Comptes rendus de la Société de biologie 2 (1906): 494–496. Serna, L. O. N de. “Carlos Chagas cidadão benemérito.” Revista brasileira de historia da medicina 10 (1959): lix–lx. Sierra Iglesias, Jobino Pedro. Salvador Mazza. San Salvador de Jujuy, Argentina, 1990. Silva, J. da, and L. Loures Filho. “Nycthemeral Variation in the Parasitaema of Trypanosoma Minasense in Naturally Infected Marmosets of the Genus Callithrix (Primates, Callithricidae).” Revista do Instituto de medicina tropical de São Paulo 16 (1974): 1–6. Sinding, Christiane. Le clinicien et le Chercheur. Paris, 1991. Souza Araujo, Henrique de. “A doença de Carlos Chagas no Paraná.” Paraná médico 3 (1919): 358a–359a.

Delaporte-Bibliography.indd 173

6/27/2012 4:07:17 PM

174

Bibliography

——— . “Congreso internacional sobre la enfermedad de Chagas (Rio de Janeiro, 1959).” In Jobino Pedro Sierra Iglesias, Salvador Mazza, su vida, su obra, redescubridor de la enfermedad de Chagas, 353. San Salvador de Jujuy, 1990. ———. “Costumes paraenses—As habitações e costumes das populações do interior, do Gurupy ao Oyapock.” Brasil-Médico (1923). Reprint. ———. “Notas epidemiologicas de Jatahy” (Estado de Paraná). A Folha Médica 2 (1919): 121a–122c. Souza Campos, E. “Alterações patológicas do tecido adiposo na moléstia de Chagas congenital experimental.” Boletim biológico 29 (1929): 75–79. ———. “Paralisia experimental determinada pelo Trypanosoma cruzi de origem humana.” Boletim biológico 9 (1927): 153–169. ———. “Transmissão intrauterina do Trypanosoma cruzi na infecção experimental do cão.” Anais da Faculdade de Medicina de São Paulo 3 (1928): 35–39. ———. “Tripanossomíase Americana congenital experimental.” Boletim biológico 26 (1929): 28–33. Souza Campos, E., and F. P. de Almeida. “Estudo histopatológico do rim na Tripanossomíase americana (moléstia de Chagas) experimental.” Anais da Faculdade de Medicina de São Paulo 3 (1928): 3–6. Souza Campos, E., and P. Toledo Artigas. “Alterações do pulmão na tripanossomíase americana experimental e contribuição para o estudo da natureza das células fagocitárias do pulmão.” Anais da Faculdade de Medicina de São Paulo 7 (1932): 3–23. Stepan, Nancy. Gênese et Evolução da Ciência Brasileira. Rio de Janeiro, 1976. Strickland, C. “On the Supposed Development of Trypanosma lewisi in Lice and Fleas; and the Occurrence of Crithidia Ctenophtalmi in Fleas.” Parasitology 2 (1909): 81–90. Strickland, C., and Nicolas Swellengrebel. “Note on Trypanosoma lewisi and Its Relation to Certain Arthropoda.” Parasitology 3 (1910): 436–453. Strong, R., G. Shattuck, J. Bequaert, and R. Wheeler. Medical Report on the Hamilton Rice Seventh Expedition to the Amazon. Cambridge, 1926. Swellengrebel, Nicolas, and C. Strickland. “The Development of Trypanosoma lewisi Outside the Vertebrate Host.” Parasitology 3 (1910): 360–389. Taliafero, W., and R. Hegner. Human Protozoology. New York, 1924. Talice, Rodolfo. Enfermedades parasitarias del hombre. Montevideo, 1944. Talice, Rodolfo, F. Medina, and F. Rial. “Primer caso de enfermedad de Chagas en el Uruguay.” Anales de la Facultad de Medicina de Montevideo 22 (1937): 238. Tanon, M. “Une nouvelle tripanossomiase de l’Amérique centrale, découverte par M. Segovia (au Salvador).” La Presse médicale (1914): 300. Tejera, Enrique. “La Tripanosomosis Americana o enfermedad de Chagas en Venezuela.” Gaceta médica de Caracas 10 (1919): 104a–108b.

Delaporte-Bibliography.indd 174

6/27/2012 4:07:18 PM

Bibliography

175

———. “La trypanosomiase américaine ou maladie de Chagas au Venezuela.” Bulletin de la Société de pathologie exotique 12 (1919): 509–513. ———. “Primer casos de Trypanosomosis americina en el Estado de Miranda.” Gaceta médica de Caracas 11 (1919): 114a–b. ———. “Un nouveau flagellé de Rhodnius prolixus, Trypanosoma (ou Crithidia) rangeli n. sp.” Bulletin de la Société de pathologie exotique 12 (1919): 527–530. Torres, Carlos B. de Magarinos. “En homenaje al prof. Salvador Mazza.” Suplemento de La Semana médica, September 21, 1949. Torres, C. Magarinos. “Alguns fatos que interessam à epidemiologia da moléstia de Chagas.” Mémorias do Instituto Oswaldo Cruz 7 (1915): 1–21. ———. “Aparelho salivar do barbeiro.” Brasil-Médico 2 (1915): 3–5. ———. “Moléstia de Carlos Chagas: Transmissão do T. cruzi pela picada do T. megista (nota preliminar).” Brasil-Médico 31 (1913): 321a–b. Vasconcellos, Figueiredo. Moléstia de Cruz e Chagas. Rio de Janeiro, 1919. ———. “Notícia histórica sobre o preparo da vacina anti-pestosa por Oswaldo Cruz, no Instituto de Manguinhos.” Memórias do Instituto Oswaldo Cruz 15 (1922): 58a–66b. ———. Boletim de Academia nacional de medicina (Rio de Janeiro) (1923): 629–656. Session of November 8, 1923. ———. Boletim de Academia nacional de medicina (Rio de Janeiro) (1923): 727–784. Session of November 23, 1923. Vasconcellos, Ivolino de. “Carlos Chagas e a medicina brasileira.” Revista brasileira de historia da medicina 10 (1959): 3–21. ———. “Oswaldo Cruz.” Actes du VIe congrès d’histoire des sciences, 2:511–517. Amsterdam, 1950. Vianna, Gaspar Oliveira de. “Algumas fases de evolução dos Tripanossomas equinum e congolense.” Brasil-Médico 25 (1911): 103b. ———. “Algumas notas sobre o ciclo evolutivo do Trypanosoma gambiense (nota preliminar).” Brasil-Médico 7 (1911): 16a–b. ———. “Contribuição para o estudo da anatomia patológica da ‘Moléstia de Carlos Chagas.’ ” In Opera Omnia, 277–294. Rio de Janeiro, 1962. ———. “Notas sobre a biologia do Trypanosoma gambiense, equinum, congolense e equiperdum.” Brasil-Médico 6 (1911): 51a–52b. Villela, Eurico. “A transmissão intrauterina da moléstia de Chagas. Encefalite congênita pelo Trypanosoma cruzi (Nota previa).” A Folha Médica 6 (1923): 41 ———. “Bocio endemic.” Revista brasileira de medicina 10 (1953): 196–226. ———. “Carlos Chagas.” Gaceta médica de Caracas (1934): 34b–46a. ———. “Carlos Chagas.” Memórias do Instituto Oswaldo Cruz 29 (1934): i–ix. ———. “Carlos Chagas.” O Hospital 5 (1935): 421–432. ———. Carlos Chagas. Rio de Janeiro, 1959.

Delaporte-Bibliography.indd 175

6/27/2012 4:07:18 PM

176

Bibliography

———. “Carlos Chagas e sua projecção no estrangerio.” A Folha Médica 25 (1936): 297a–303b. ———. “Da ocorrência da doença de Chagas nos hospitaes de Belo Horizonte e na população de seus arredores.” A Folha Médica 11 (1930): 229–235. ———. “Forma aguda da moléstia de Chagas: Primeira verificação no Estado de São Paulo.” Brasil-Médico 32 (1918): 65. ———. “Lésions histo-pathologiques dans la paralysie expérimentale à Schizotrypanum cruzi chez le chien, nature des cellules contenant le parasite dans le système nerveux central.” Comptes rendus de la Société de biologie 93 (1925): 133–135. ———. “Moléstia de Chagas. Descrição clínica.” A Folha Médica 4 (1923): 33–35, 41–43. ———. “Paralysie expérimentale chez le chien par le Trypanosoma cruzi.” Comptes rendus de la Société de biologie 91 (1924): 979–983. Villela, Eurico, and Emmanuel Dias. “Localisation des formes de multiplication du Schizotrypanum cruzi dans la peau et dans les muqueuses de chiens expérimentalement infectés: Parasitisme de la cellule épithéliale de l’épiderme.” Comptes rendus de la Société de biologie 117 (1934): 501–504. ———. “Sur la formation d’ulcérations chez les animaux infectés par Schizotrypanum cruzi.” Comptes rendus de la Société de biologie 117 (1934): 394–396. Villela, Eurico, and Carlos B. de Magarinos Torres. “Estudo histopatológico do sistema nervoso central em paralisia experimental determinada pelo Schizotrypanum cruzi.” Memórias do Instituto Oswaldo Cruz 19 (1926): 175–193. ———. “Lésions histo-pathologiques dans la paralysie expérimentale à Schizotrypanum cruzi chez le chien: Nature des cellules contenant le parasite dans le système nerveux central.” Comptes rendus de la Société de biologie 93 (1925): 133–135. Walker, Myron L. “Schizogony of the Trypanosoma evansi in the Spleen of the Vertebrate Host.” Philippine Journal of Science 7 (1912): 52–53. Wenyon, Charles. “Experiments on the Transmission of Trypanosoma lewisi by Means of Fleas.” Journal of the London School of Tropical Medicine 2 (1912–1913): 119–123. Woodcock, H. “The Haemoflagellates: A Review of Present Knowledge Relating to the Trypanosomes and Allied Forms.” Quarterly Journal of Microscopical Science 50 (1906): 152–331. York, W. “On Human Trypanosomiasis in Peru.” Annales of Tropical Parasitology 13 (1920): 459–460. Zembra, Edouardo R. La enfermedad de Chagas, su historia. Buenos Aires, 1944. Zuccarini, J., and J. Oyarzabal, J. “Sur l’existence du Trypanosoma cruzi à Cordoba (R. A.).” La Folia biologica (1933): 151.

Delaporte-Bibliography.indd 176

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index

Addison, T., 58 Affonso, P. de, 7, 16, 17 Albarran, J., 15 Alves, R., 6, 20 Alvim (prefect), 16 Andrade, N. de, 14, 17 Aragão, H., 20, 52, 53, 56, 74, 94, 96, 98, 99 Araujo, S., 1, 93 Artigas, T., 109 Austregesilo, A., 35, 36, 37, 58, 117 Bachelard, G., x Baeta Vianna, J., 111, 112 Bagshawe, A., 74, 77 Balfour, A., 74, 77 Basso, G., 126, 131 Basso, R., 126, 131 Bayma, T., 93 Bibiloni, A., 126 Borzone, R., 111 Bourneville, D.-M., 59 Breinl, A., 77 Bruce, D., 26, 27, 52 Brumpt, E., 24, 25, 71, 74–77, 79, 80, 81, 88, 90, 105, 107–8, 117, 123, 131, 134

Bruni, N., 107 Buffard, M., 26 Caceres, R., 130 Campos, F., 108, 109 Canal-Feijoo, B., 125 Canguilhem, G., x Carini, A., 25, 56, 74, 108, 110, 111 Carré, C., 8, 16 Castellani, A., 26 Cerqueira, D., 25 Chagas, E., 106, 108, 109, 126 Charcot, J.-M., 59, 63 Chatton, E., 66 Chaves, L., 91, 112 Clark, H., 111 Coda, M., 111 Courrier, R., 66 Coursey, E. de, 110 Couto, M., 35, 36, 37, 58, 60, 96, 117 Crowell, B., 110 Cruz, B., 16 Cruz, O., 3, 7, 8, 13–22, 29, 31–47, 73, 96, 98, 100–2 Cunha, A. M. da, 102

177

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178

Index

Darwin, C., 6 Deane, L., 25 Delanoës, M., 56 Dias, E., 2, 16, 105, 106, 108, 109, 113, 115–17, 123, 124, 126, 129–31 Dios, R., 108, 110, 111 Donat, F., 108, 110 Dowell, M., 96 Duclaux, E., 14 Dumas, J.-B., 19 Dunn, L., 111 Duque, H., 96 Duruy, V., 19 Dutton, J. E., 26 Elmassian, M., 26, 69 Escomel, E., 74, 92, 110 Evans, G., 26 Faria, R., 14, 20 Figueira, F., 35, 58 Fodéré, F., 59, 83 Fonseca, M. da, 93, 96, 102 Forde, M., 26 Foucault, M., 137 Fraga, C., 19, 36, 37, 38, 96, 98 Gaillard, H., 108 Gaminara, A., 108 Geer, C. de, 6 Geoghegan, A., 111 Graf, M. von, 83 Grasset, E., 66 Greig, E., 27 Gruby, D., 26 Gull, W., 59 Gumilla, J., 5 Guyon, J. F., 15

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Hartmann, M., 8, 21, 50, 51, 52, 53, 77 Herr, A., 131 Hindle, E., 77 Hoare, C., 24, 113 Horta, P., 74, 93, 94, 96, 101 Iglesias, S., 126 Izaguirre, A., 130 Jeandelize, P., 66 João VI, 7 Jörg, M., 125, 131 Kitasato, S., 16 Kleine, F., 52 Koch, R., 52, 86 Kocher, E., 59 Kofoid, C., 108, 110 Kraus, R., 73–78, 83–86, 89–91, 93–95, 97, 99, 105–7, 111, 120, 121, 134 Lacorte, J., 111 Lanfranchi, A., 107 Latreille, P. A., 6 Laveran, A., 14, 25, 66, 117 Lessa, G., 102 Lewinsohn, R., 22, 24 Lizarraga, R. de, 5 Lobo Leite, A., 105, 106, 112, 113, 116 Lozano, N., 76, 77, 86 Lutz, A., 93 Maciel, J., 93 Maggio, C., 73, 75, 76, 87, 89, 105 Martinetti, C., 111 Mayer, M., 74, 77, 107, 109, 110 Mazza, S., 103–6, 111, 118, 122, 124–31

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Index McCarrison, R., 65, 74, 75, 78 Meirelles, E., 96 Migone, L., 69, 93 Miller, J., 111 Minchin, E., 74, 75, 77, 79 Miquel, S., 14 Morais, L., 3 Moreira, J., 35, 36, 58 Morel, L., 66 Motta, C., 27 Mülhens, P., 108, 110, 111 Muniz, J., 108 Munk F., 111 Nabarro, D., 25, 27 Nascimento, A., 96 Nattan-Larrier, L., 107 Neiva, A., 18, 20, 69, 70, 71, 73, 74, 76, 93, 101, 107 Niño, F., 17, 108, 111, 118, 128, 129 Noguchi, H., 110 Ogier, W., 14 Oliveira, G. de, 93 Olle, R., 131 Ord, W., 59 Oswaldo Cruz Institute, 2, 10, 17, 20, 39, 45, 46, 125 Pamplona, A., 96 Parma, B., 124 Pasteur, L., 13, 15, 17, 18 Patton, W., 77 Pedro II, 7, 13, 14, 18 Peixoto, A., 74, 95, 96, 102 Penna, A., 20 Penna, B., 27

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179

Penna de Azevedo, A., 105, 106, 110, 113, 116, 120, 121 Pereira, M., 35, 36, 37, 58, 60, 99, 117 Perleth, M., 22, 48, 103, 104 Pettit, A., 25 Piraja da Silva, M., 80 Preto, R., 93 Prowazeck, S. von, 8, 20, 21, 50, 51, 52, 77, 79 Reichnow, E., 111, 114 Reverdin, J., 59 Rocha-Lima, H. da, 8, 18, 74, 75, 77, 96, 107, 109, 110 Rodhain, J., 25 Romaña, C., ix, x, 9, 48, 74, 104–6, 114–34, 136, 137 Roubaud, E., 53 Rouget, J., 26 Roux, P.-P.-E., 14–16 Salvin-Moore, J., 77 Santos, F. dos, 13, 16 Schaudinn, F., 7, 8, 20, 50–54, 57, 77–79, 108 Schneider, G., 26 Segovia, J. C., 74, 92 Sergent, E. (Edmond), 77 Sergent, E. (Etienne), 77 Silva, P. da, 81 Souza Araujo, H. de, 1, 93 Souza Campos, E., 107, 109 Strickland, C., 77, 79, 80 Swellengrebel, N., 79 Talice, R., 125 Tejera, E., 74, 93 Torres, M., 90, 102, 108, 109

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180

Index

Valentin, J. M., 26 Vasconcellos, H. de, 16, 35, 74, 76, 95–102 Vianna, G., 54, 56, 61, 74, 77, 101, 107, 110–12 Vibert, C., 15 Villela, E., 72, 74, 93, 101, 102, 107, 109, 112, 113, 116

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Walker, M. L., 6 Wenyon, C., 25 Yersin, A., 7 Zembra, E. R., 131 Zuccarini, J., 108, 110, 111

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Georges Canguilhem, Knowledge of Life. Translated by Stefanos Geroulanos and Daniela Ginsburg, Introduction by Paola Marrati and Todd Meyers. Henri Atlan, Selected Writings: On Self-Organization, Philosophy, Bioethics, and Judaism. Edited and with an Introduction by Stefanos Geroulanos and Todd Meyers. Jonathan Strauss, Human Remains: Medicine, Death, and Desire in NineteenthCentury Paris. Georges Canguilhem, Writings on Medicine. Translated and with an Introduction by Stefanos Geroulanos and Todd Meyers. Juan Manuel Garrido, On Time, Being, and Hunger: Challenging the Traditional Way of Thinking Life. Catherine Malabou, The New Wounded: From Neurosis to Brain Damage. Translated by Steven Miller. François Delaporte, Chagas Disease: History of a Continent’s Scourge. Translated by Arthur Goldhammer. Pamela Reynolds, War in Worcester: Youth and the Apartheid State.

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