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Tropical medicine and bacteriology in Boston and Peru: studies of Carrión's disease in the early twentieth century.

Recent historical studies on medicine as a tool of empire have underlined the importance of local perceptions and responses when analysing the strategies and impact of European and North-American powers in various regions of the globe.1 These studies have suggested that the development of tropical medicine has not been a one-way street, that the rich texture of local societies occupied a central place in this process, and that authority had to be negotiated and accommodated by recipients who were able to redefine imported ideas and institutions.2 This article adds to this literature by using comparative history and by suggesting that developments in the so-called "periphery" provide crucial insight into the work of the metropolitan scientific centres. This article analyses the achievements and difficulties confronted both by Peruvian researchers trying to reinforce a local medical culture in a poor country and by U.S. investigators endeavouring to persuade philanthropic sponsors of the need to establish tropical medicine as an independent academic subject. The story takes place in early twentieth-century Peru, a country that in the wake of its defeat in the War with Chile (1879-1883) initiated a process of national reconstruction and modernization based on an agreement with foreign bondholders. This included ceding control of its railroads for sixty-six years, the arrival of major U.S. investments which displaced the dominant

position of British interests in the country, the export of a variety of both agricultural and mineral products that reduced its vulnerability to international price fluctuations, and the emergence of a civilian political elite that ruled the country between 1895 and 1919 under a democratic system of controlled elections.3 Carri6n and the Disease The eponym Carrion's disease was used to honour a medical student who was interested in understanding two diseases which were considered to be different clinical entities: verruga peruana (literally Peruvian wart) and Oroya fever. The former had been known since pre-Hispanic times, and was recognized as a nodular eruption on the skin which might last from a few weeks to several months. These skin eruptions were unlike those produced by other types of warts found in the rest of the world (hence the name verruga peruana).5 Factual data on Oroya fever dated from 1870, when an epidemic of fever and anaemia killed thousands of workers who were building the trans-Andean railway from Lima to La Oroya, a major mining town. Because the epidemic was not followed by a geographical spread of the disease, medical authorities named it "Oroya fever".6 The delay in recognizing Oroya fever (in contrast with verruga) is attributed to the fact that its main symptoms, fever and anaemia, could be confused with many diseases.
The government, the British Central Railroad Company, which operated all trains in the country, and, after 1901, the U.S. Cerro de Pasco Cooper Corporation, which used the Andean Central Railway to get its minerals to Lima, were very much concerned by Oroya fever because the Central Railway was the chief artery of transport between the coast and the mining centres in the central Andes. Many lives were lost to the disease every time the line was repaired or rebuilt.
Verruga peruana and Oroya fever attracted the attention of students and professors of the School of Medicine in Lima which was part of Peru's main University, San Marcos, and the only medical school in the whole country. In August 1885, a medical student, Daniel A Carrion, seeking to understand the pre-eruptive symptoms of verruga peruana, asked a fellow student to inoculate him with blood from a hospital patient afflicted with the disease. After an incubation period of twenty-one days, Carri6n showed no sign of warts, but he began to suffer from fever and anaemia, the two main symptoms of Oroya fever. A few days before he died, Carrion claimed that both diseases had the same origin.7 Other Peruvians doctors had previously maintained that verruga peruana and Oroya fever were manifestations of the same disease, but these statements appeared only as comments made in medical circles.8 Initially, some authorities reacted to Carrion's death negatively.9 This was partly because Carrion did not use in his inoculation any of the scientific resources available at the time, such as microscopic observation of the inoculated blood or bacteriological blood cultures. A delayed autopsy produced insufficient evidence to conclude whether Carrion died of Oroya fever or of a form of septicaemia.10 In response to the criticism, and to the threat of a lawsuit by the sub-prefect of Lima, Carrion's fellow students launched a campaign extolling him as a hero of science who had demonstrated that the two native illnesses shared the same origin.
Within a few years, Carrion's experience became an exemplary component of an emergent medical culture in Peru. Carrion's behaviour was presented as similar to that of famous European researchers of the nineteenth century who had experimented on themselves and their associates with virulent microbes.' 1 Thus Carri6n was converted into a "6martyr" of Peruvian medicine and his inoculation became a "sacrifice" for science.12 Subsequently, Peruvian physicians used the term "Carri6n's disease" rather than verruga peruana or Oroya fever, and elaborated a so-called "unifying" (in Spanish unicista) explanation of the origin of the two diseases. 7 The literature on Carri6n is abundant and usually repetitive. See Luis Antonio Eguiguren, El Estudiante de medicina Daniel A. Carri6n (proceso judicial sobre su gloriosa muerte), Lima, Editorial Aurora, 1941; Juan B Lastres, Daniel A. Carri6n, Lima, Editorial San Marcos, 1957; Francisco Linares Cabrera, 'Influencia de la vida y obra de Daniel A. Carri6n en la historia de la medicina peruana', BA thesis, Universidad 9 According to a former dean of the Medical Faculty: "Science has gained little, discredit of the profession has increased and the precious existence of an unwary young student has been snatched away." Ignacio La Puente, 'Una vfctima de la ciencia', El Campe6n, 6 Oct. 1885, reproduced by Casimiro Medina (ed.), La verruga peruana y Daniel A. Carri6n, Lima, Imp. del Estado, 1886, pp. 67-8.
10 Myron G Schultz, 'Daniel Carri6n's experiment', New England J. Med., 1968, 278: 1323-6. 1 On self-experimentation, see Lawrence K Altman, Who goes first?: the story ofselfexperimentation in medicine, New York, Random House, 1986. 12 For an illuminating account of the process of the glorification of Carri6n, see Uriel Garcia Caceres, 'Historia crftica de Daniel A. Carri6n y de la medicina de su 6poca', PhD diss., Universidad Peruana Cayetano Heredia, 1970. The appearance of such a hero contributed much to the professional identity and public legitimation of Peruvian medical doctors. During the late nineteenth century in the major Peruvian cities, San Marcos' physicians had to compete with Indian healers (the occupations of herbalist, healer and sorcerer were not strictly separated in the Indian culture), itinerant quacks (who were sometimes Europeans) and Chinese herbalists (who were part of an urban Chinese colony created by the importation of Chinese indentured labour during the nineteenth century). The assumption that modem medicine and western science was superior to any other form of knowledge was instrumental in displacing those health practitioners who were foreigners or who were not members of the upper and middle classes. Furthermore, Carri6n's experience gave physicians a hero, casting around them an aura of civic virtue.
After Carri6n, Peruvian doctors regarded the two diseases as the severe and the mild forms of the same illness. The development of a wart eruption was regarded as an indication of a favourable outcome, and irritants were applied to the skin of patients with Oroya fever to induce early appearance of the skin lesion. The first comprehensive description of Carri6n's disease, written in French and published in Paris by the Peruvian physician Emesto Odriozola, drew the attention of European scientists to a peculiar disease believed to occur only on the western slopes of the Andes at altitudes of between 800 and 1,500 metres.13 Odriozola's book was a landmark for Peruvian physicians who championed a Frenchinfluenced medical culture based on a combination of clinical and geographic observations that did not seek to integrate the medical systems used by indigenous healers. 14 This culture emphasized the specific climatic characteristics of Peru like the fact that, despite its location in a tropical latitude, the coast is mostly arid, has a mild temperature and little rainfall because of the combined effects of the Andes and cold Pacific currents. The book was also instrumental in underlining the beliefs of Peruvian physicians that the understanding of the unique medical geography of Peru demanded prolonged clinical practice and observation and that usually foreign physicians were ignorant of the crucial relationship between Peruvian topography and illness, partly because they came with preconceived medical ideas or remained only briefly in the country.
Odriozola's work sustained the belief in the etiological unity of the two illnesses using only clinical and geographical evidence (the two conditions occurred in the same locations). In addition, he and other Peruvian physicians, such as Edmundo Escomel, noted that persons who contracted verruga did not suffer from a second attack; nor did they contract Oroya fever, and vice versa. Despite the fact that Escomel had trained in France as a bacteriologist, most of his studies on Carrion's disease were of an anatomical 13  The fragile margin between basic and applied research in their specialty permitted bacteriologists to attract support for research by arguing that science was a powerful tool in the detection, prevention and cure of infectious diseases which ravaged the country. More regular support was given to bacteriology because of the need to produce sera and vaccines, study native illnesses, and control the use of insecticides and disinfectants. These measures were considered necessary to protect the urban and port populations, to attract coveted European immigrants, and to foster trade and investment in the rising export economy of Peru. Thus, by the early 1900s bacteriological laboratories existed at the Instituto Nacional de Vacuna y Seroterapia (which depended upon the Direccion de Salubridad Piblica, a branch of the Ministry of Development); the Instituto Municipal de Higiene, which was directed by the Italian bacteriologist Ugo Biffi; and in some hospitals including the magnificent Hospital Dos de Mayo, used for clinical instruction, and the Hospital Guadalupe at Callao, the chief seaport of Peru located eight miles west of Lima.
Some of the physicians trained in bacteriology by Matto at San Marcos University found positions in these new institutions. Oswaldo Hercelles, whose thesis was an histological study of Carrion's disease, became, in 1906, director of the bacteriological laboratory of the Dos de Mayo hospital, where he was able to form a small staff of researchers. Hercelles' career suggests the lack of specialization of the first Peruvian bacteriologists and their combination of different medical paradigms since, in addition to his position as chief bacteriologist at the hospital, from 1910, he was also professor of Early Peruvian bacteriologists displayed originality and perseverance in their work. By the turn of the century, bacteriological research could be undertaken at the centres mentioned above, each of which possessed such essentials as microscopes, glassware, bacteriological stains, specialized literature and trained staff. Peruvian scientists allocated these resources to the study of native illnesses, in particular Carri6n's disease. Solving its etiology offered the opportunity to associate the name of the discoverer with an emerging national medical tradition. Peruvians were aware that European, American and Japanese scientists were determining the etiology of many infectious diseases, but the search for the causative agent of verruga peruana and Oroya fever was a research area where competition was initially limited to Peruvians. As in other cases of emerging disciplines in Latin America, the bacteriology of a disease specific to a country became the focus of a local research tradition because of the comparative advantages enjoyed by local scientists.20 The medical theses of San Marcos stand out among the first bacteriological studies of Carri6n's disease. Notable among them was that of Alberto Barton, born in 1871, a son of British immigrants, who became the key figure among local bacteriologists. In his 1901 thesis, Barton identified and described foreign bodies in the red blood cells of Oroya fever patients. Barton considered these bodies to be the causative microbe of Carrion's disease, and they became known as the "Barton bacillus".2' However, Manuel 0 Tamayo, who studied at the Pasteur Institute in Paris and replaced Biffi as chief bacteriologist at the Instituto Municipal de Higiene in 1903 when the Italian returned home, demonstrated that although the so-called "Barton bacillus" existed, it was not the pathogenic agent of Carri6n's disease.22 Later research proved that Barton had described an already known bacteria of the coli-typhoid group.23 For years, Tamayo and Julio Cesar Gastiaburu, his colleague at the Instituto, argued that Barton's bodies were red cell alterations, of value in the diagnosis of Oroya fever, but not the causative agent.24 Barton recognized his mistake, and decided to complement his training by seeking a government fellowship to study at the School of Tropical Medicine in London. In 1905 he was back in Lima, working again on the etiology of Carri6n's disease. Based on new studies, Barton announced in 1909 the discovery of the causative agent.25 This time Barton was certain that the filamentous bodies he had identified in the blood of Oroya fever patients, in the form of bacilli, were different from any other known organisms. It is interesting to note that the central aspect of Barton's work was its morphological 20 A similar case is the work of the Brazilian descubrimiento de la bartonella', PhD diss., Carlos Chagas's on Trypanosoma cruzi. See  description of a new microorganism. Barton limited himself to describing the exterior characteristics of the bacilli and to indicating the most appropriate stains for their observation. He pointed out that the bacilli multiplied themselves in the Oroya fever victims, and decreased in numbers, until they almost disappeared, when the patients broke out in warts. From this observation he deduced that Oroya fever was an hypertoxic form of verruga peruana, in other words, that both clinical conditions were different manifestations of the same disease.
Later Barton was credited with establishing that Carri6n's disease has a first, hematic, phase, known as Oroya fever, in which the intracellular bodies parasitize and destroy the red blood cells of the patient, who manifests extreme anaemia. Oroya fever was considered generally fatal (before antibiotics the mortality rate has been estimated at between 30 to 70 per cent of severe cases). Verruga peruana, the second phase, is characterized by cutaneous eruptions and is usually not fatal. This phase generally signifies the patient's recovery when the Bartonella bacillifornis bacteria in the blood reduce in number or disappear.26 However, most contemporary Peruvian researchers did not accept Barton's findings. For many, the microbes reported by Barton in 1909 were no more than cellular degenerations, of value in the diagnosis of Oroya fever, but not the causative agents of the disease.27 For example, Carlos Monge Medrano, who studied at the School of Tropical Medicine in London between 1911 and 1912, wrote in 1912, "Up to the present time no one has succeeded in finding the specific cause of the infection".28 This conclusion can be understood as a result of the mistrust produced by Barton's earlier mistake and, even more important, his peripheral position in the fragile group of Peruvian bacteriologists. These scientists were all concentrated in Lima, they did not have a local specialized journal but used the main medical journals like La Cr6nica Medica, and never organized an independent scientific society but were members of general medical societies like the Academia Nacional de Medicina and the Sociedad Medica Union Femandina.
After returning from England, Barton was unable to find a position in the university and worked for years as the director of the laboratory of the Hospital Guadalupe of Callao, a second-class facility compared to other laboratories in Lima. Barton gave little importance to publication while other bacteriologists were remarkably overproductive. Barton's entire scientific work between 1901 and 1946 (mostly during the first two decades of the twentieth century) amounted to a total of 13 publications (including books, pamphlets and academic articles). By contrast, Edmundo Escomel, a contemporary who worked not only in bacteriology, had by 1929 a total of 354 medical and scientific publications to his credit. Monge Medrano, thirteen years younger than Barton, published between 1912 and 1925 a total of 54 articles. Monge's work was mainly related to tropical diseases and was done before the research in high-altitude physiology which made him well-known all over the world.29 For Peruvian scientists such as Escomel and Monge Medrano overproduction was crucial to attract local recognition and support, although it was frequently achieved through studies of very specific clinical cases and repetition of data. Barton's low rate of publication reduced his visibility and made recognition more difficult. Around 1920, he abandoned research and medical practice to work in the soft drinks industry, becoming a successful entrepeneur in Peru.
While Peruvian bacteriologists were uncertain of Barton's findings of 1909, during the 1910s European and U.S. investigators became interested in Carri6n's disease. One of the first Americans who worked on it was the entomologist Charles Townsend. He was hired by the Peruvian government in 1913 for a series of studies, including a search for the vector of Oroya fever. Some local physicians thought a mosquito was the carrier.30 Believing that Carrion's disease and Rocky Mountain spotted fever had a similar mode of transmission, Townsend began by considering ticks and lizard mites as probable vectors.31 After obtaining negative results, he searched for an insect whose distribution and habits fitted the geography and night-time exposure of humans. Townsend identified a nocturnal sandfly, known as titira, which was the vector of Oroya fever (then named Phlebotomus verrucarum and today known as Lutzomyia verrucarum).32 Another American scientist who became very interested in Carrion's disease was Richard P Strong. In 1913 a commission of Harvard scientists directed by Strong visited Lima and confirmed that the bacillus discovered by Barton was a new organism. Only then was Barton given local recognition for his finding of 1909. Strong was a leading figure of tropical medicine in the USA, and his involvement with a Peruvian disease is better understood against his wider background.

Strong and Harvard
Trained at Johns Hopkins Medical School, Richard P Strong was a physician serving as a first lieutenant in the Army when in 1901 he was appointed to head a board to investigate tropical diseases in the Philippines. His work was part of the military concern with diseases in occupied tropical and semi-tropical territories like Cuba and the Philippines. After finishing his investigation, he was induced to resign from the Army to organize and 29 The number of publications is taken from the detailed accounts that appear in 'Bibliograffa de Alberto Barton'-, Anuario  contact with the tropics.39 The construction of the Panama Canal and the foreseeable marked increase in shipping reinforced this argument. With the advent of the Canal, yellow fever regions such as the Caribbean would be more fully integrated into the world's networks of commerce and travel. Tropical Asia, until then free of yellow fever, possessed all the preconditions needed for an epidemic of the disease. There was also a possibility of reinfection of the U.S. South itself, a sub-tropical region that had experienced epidemics of yellow fever until the first years of the twentieth century.
Strong believed that there was a growing professional market for graduates in tropical medicine. The argument was clearly explained by American missionaries (deeply involved in evangelical work overseas) who supported the establishment of tropical medicine at Harvard: The services of physicians especially trained in the diseases more commonly encountered in hot countries are frequently sought by various commercial firms of different countries who do business in the tropics and who own mines or plantations or who employ a large amount of native labor ... Strong also appealed to local pride, arguing that Boston should have a school of tropical medicine of the rank of those already existing in London, Liverpool, Hamburg, and Brussels. Following these arguments, Harvard University made an offer to President Woodrow Wilson to train government medical officers in the Department of Tropical Medicine before they were assigned to duty in the tropics.4' Finally it appeared that Boston and Harvard offered good opportunities for supporting tropical medicine. The city was one of the most important Atlantic seaports, receiving a considerable number of cruises from tropical regions of the world. It was also the headquarters of several American companies active in the tropics, including the United Fruit Company. In addition, Harvard had a number of professors and institutions with a strong interest in bacteriology, entomology, zoology, botany and other fields related to the tropics such as those at the Bussey Institute, the Gray herbarium, the Botanical Garden and Museum, the Arnold Arboretum, the Peabody Museum of Anthropology and other University museums. The Medical Faculty included leaders in public health and tropical science such as Milton J Rosenau professor of preventive medicine and hygiene, George C Whipple, the Gordon McKay professor of sanitary engineering, Harold C Ernst, the first professor of bacteriology, and Theobald Smith, the George Fabyan professor of comparative pathology. When the Department opened its doors, Smith, Rosenau, and Ernst were part of an advisory board to assist Strong, and courses in the new Department were offered by professors from the departments of zoology, entomology, botany, physics, As the first task of the Department, Richard Strong decided to organize a scientific expedition to study diseases along the Pacific coast of South America, especially in Ecuador and Peru. Using an argument parallel to that of many public health officers who stressed the economic advantages of sanitation, Strong contended that his investigation was crucial for U.S. economic expansion: "the nature of the diseases which exist in many of these pest-holes must first be investigated . . . labor and capital need only follow."43 The expedition was planned for the summer of 1913, before the beginning of instruction, and during a period when the Department needed to show, according to the Dean, that "significant accomplishments" could be done "with a small amount of money."44 Ecuador and Peru were chosen, first, because locations like the port city of Guayaquil in Ecuador were considered hotbeds of tropical diseases and provided opportunities to pick up materials for use in the instruction of Harvard students. Second, little was known about this region in contrast with other areas of Latin America, which had been studied by the U.S. Army and the United Fruit Company and by the active indigenous scientific community of Brazilian scientists.45 Third, the mystery surrounding Oroya fever and verruga peruana represented a challenge and an opportunity to discover a new microorganism. Finally, Strong also underlined the potential interest of American companies in the Amazon region of Peru which comprised more than 60 per cent of the country and was the home of the rubber tree.46 According to Strong the western side of South America was: "from a commercial standpoint the largest underdeveloped area of the Western hemisphere".47 The other members of the expedition were also from Harvard: Ernest Tyzzer, assistant professor of pathology, Charles Brues, assistant professor of entomology, and A W Sellars, associate professor of tropical medicine. In Peru, the Americans included in their team the Peruvian bacteriologist Julio Cesar Gastiaburu, then director of the laboratory of the Instituto Municipal de Higiene, who co-signed some of the final reports. Harvard provided some funds for the expedition and the United Fruit Company and Pacific Steam Navigation furnished free transportation from Boston to Peru. To reciprocate, Strong agreed to inspect some of the eight hospitals established by United Fruit in Latin America.48 The expedition visited Jamaica, Panama, Colombia, Ecuador, and reported on the diverse diseases encountered. Their primary mission, however, was in Peru where they studied verruga and Oroya fever. They also gave some attention to the native version of leishmaniasis, locally known as uta, an infection caused by a flagellate protozoan that 43  parasitizes the tissues (although the etiology of this disease became clear only in the late 1920s). In Lima, Peruvian authorities and physicians gave support, and the British Central Railroad Company provided facilities for studies carried out between Lima and La Oroya. Strong and his associates worked at the laboratory of the Instituto Municipal de Higiene where they experimented with animals and an inmate from the insane asylum.49 Interestingly, in the English version of the report the inmate was presented as a volunteer, probably because of concern about public reaction to the use of humans in medical experiments. Strong confirmed Barton's Oroya fever findings, and his observations further indicated that the red cell structures reported by Barton in 1909 could hardly be degeneration products, as Tamayo and Gastiaburu had argued, since they exhibited motility, i.e. independent movement. Later studies indicated that Barton's bodies also occurred in tissue cells not associated with red blood cells. In honour of its discoverer, Strong proposed the creation of a new genus and named the Oroya fever microbe Bartonella bacilliformis.50 In the final report published in English, Oroya fever was fully described and elegantly illustrated.
The Harvard Commission vigorously questioned the Peruvian medical belief in the identity of the two illnesses involved in Carrion's disease. According to Strong, Barton had discovered the causative agent of Oroya fever, not the one that caused verruga peruana. Strong's experiments failed to find Bartonella bacilliformis, or any other microorganism, in the blood of persons suffering from verruga or in that of animals with experimental verruga. However, they did succeed in transmitting the "virus" of verruga to experimental animals and to the asylum inmate, concluding that the disease was inoculable, but they failed to obtain cultures of the organism.51 Strong's whole work was consonant with that of many bacteriologists of the time who placed great importance on standardized methods (basically the use of the Koch postulates), and who regarded it as unlikely that a single disease could manifest itself in two different ways.52 Only years later did new studies such as those on chicken pox and shingles, which are expressions of the same herpes virus, show the range of manifestations of a single pathogen. Strong believed that verruga must originate from a different, and still unknown, virus.
Even the validity of Carrion's experiment was contradicted because the asylum inmate, inoculated by Strong with tissue juice from a wart nodule, developed no symptoms of Oroya fever and had only a mild verrucous lesion at the site of the inoculation. According to Strong this experiment showed conclusively that verruga and Oroya fever were two different diseases. In his report, Strong carefully stressed that, although he admired Daniel Carrion, his death proved nothing. Strong suggested that Carrion probably died of "an acute form of septicemia", or that the patient whose blood Carrion had used might have 49  Before returning to the States, Strong read in a local newspaper that Peruvian researchers had performed some of his experiments (such as the transmission of verruga to rabbits) without acknowledging his own earlier work. He hastily sent a cablegram to the Dean of the Harvard Medical School announcing his conclusions. The apparent tension between Americans and Peruvians was expressed more clearly in a letter written in Lima by Strong to Shattuck, his mentor at Harvard: I felt it necessary to send the cablegram to ensure priority of our work for the University, as the Peruvian doctors here are watching our work very closely, and have apparently tried to repeat every experiment which they see us do ... and of course would prefer that we should not have anything new which they were not able to report upon.54 A version of the cablegram was promptly published in a Harvard magazine celebrating the "great step forward" in research and the "success [that] crowned the first enterprise" of Harvard's tropical medicine department.55 In his annual report, the Dean of the Harvard Medical School applauded Strong's achievements.56 Upon returning to Boston, Strong published articles in the Journal of the American Medical Association and a preliminary report, which appeared in 1915 as a handsome book, that stressed that "the discoveries made by the expedition should serve to emphasize the importance of sending from the School to the tropics other expeditions of this nature".57 Strong sent a copy of the report to thirty-seven prominent Bostonians, thanking them for their support of the Department of Tropical Medicine "in its early struggling years".58 Complimentary replies emphasized the value of Strong's work in terms of national interest and American largesse.59 The perception of an early "success" for the Department of Tropical Medicine was instrumental in creating new alliances favouring academic tropical medicine at Harvard, at least for a while. In 1914, the Deans of the Medical School and the Graduate School, felt that "success in the development of the Department of Tropical Medicine was most likely to be attained if Dr. Strong is given as free a hand as possible to develop his ideas".60 His main idea, approved in 1914, was the transformation of the Department of Tropical Medicine into an independent School offering doctoral degrees in tropical medicine. 53  Strong received further recognition in 1914, when he was appointed chief of a new subdepartment of tropical medicine at the Massachusetts General Hospital, and consulting physician in tropical diseases at the Boston City Hospital. In the same year, he was elected President of the American Society of Tropical Medicine, and director of the laboratories of the hospitals and research-work stations of the United Fruit Company. As director he, and his students, could work in any of the hospitals that United Fruit managed in Costa Rica, Panama, Guatemala, Colombia, Cuba and Honduras. Strong was very pleased with the latter connection because it fulfilled his "desire to place candidates for the degree of . The latter emphasized industrial hygiene, which was perceived by some as more immediately relevant to the economic needs of the U.S. than tropical medicine. An additional problem for the School of Tropical Medicine was the small number of students enrolled at Harvard, and the difficulties involved in finding them positions abroad, partly because, unlike Britain and France, the United States barely possessed a formal empire, and because, according to one public health professor: "In many countries, public health positions are more or less pawns in the political game'.M After the creation of the School of Hygiene and Public Health at Johns Hopkins University in 1916, which received sizeable donations from the Rockefeller Foundation, tropical medicine began to be perceived in the U.S. as an academic discipline that was not well defined and that did not merit independent institutional development because it 61  For years Strong used the materials collected in Peru on Oroya fever, verruga, and leishmaniasis to instruct students who were trained according to the principle that each disease responded to a single causative organism. The general course of tropical medicine was taught by Strong himself, who presented a comprehensive review of all diseases that might be considered tropical, including dysenteries, yellow fever, cholera, plague, malaria and verruga peruana. However, with the exception of an article dated 1924, Strong did not return to study Carrion's disease until the late 1930s.
After 1915, Strong was very active in organizing new expeditions to other areas of the world, such as Serbia, the Amazon, the Belgian Congo, and Guatemala, with the purpose of investigating new diseases and obtaining teaching materials.67 These expeditions increased his academic prestige and validated his scientific claims among U.S. scientists. Meanwhile, Peruvian bacteriologists were digesting Strong's 1913 conclusions and Hideyo Noguchi, a Japanese-American scientist, appeared on the scene.
Noguchi and the Peruvians Strong's conclusions had a contradictory impact on Peruvian medical circles. On the one hand, a senior prestigious foreign scientist had recognized excellence in a local researcher; on the other, Strong had denied the Peruvian physicians' belief in the etiological unity of Oroya fever and verruga peruana. The nationalistic and professional tradition partly based around Carrion's "sacrifice" held back Peruvian physicians from accepting the possibility that Carri6n had died in vain. The bacteriologist Oswaldo Hercelles declared that Strong studied only one human case which was mistakenly diagnosed as verruga and declared that his conclusions "injured" the national pride of Peruvian doctors.68 Moreover, Strong's conclusions were considered an attack on the local medical tradition that believed that because of climate and topography some native diseases had particular manifestations. According to Odriozola, the "intervention of bacteriology" was disturbing "profound clinical notions", and he raised his voice against Strong's "dissociative crusade".69 In addition, when in 1916 the physician Julian Arce inaugurated the new chair of tropical medicine at the University of San Marcos, he argued that Carrion's disease was the best example among tropical diseases of the "absolute dependency" of microorganisms and vectors on geographic distribution and local climatic conditions.70 This attitude continued in a major work on the medical geography of Peru published in 1925 by the directors of the Direccion de Salubridad Publica and the Instituto Nacional de Vacuna and Sueroterapia, who argued that local surveys made a strong case in favour of the common origin of verruga and Oroya fever.71 In the same year, Monge Medrano wrote a general description of the disease for a German journal in which he emphasized that Strong had studied "one [human] case" for only three months and that his statements on a dual etiological origin were not sustained by the clinical and epidemiological observations of Peruvian physicians.72 Most foreign scientists dismissed the Peruvian complaints as an indication of a backward scientific tradition in which nationalistic concerns took the place of research. An exception was Charles Townsend, who shared the Peruvian belief of a unified etiology for both diseases. His disagreement with Strong is understandable, considering he was exposed for longer to the environment where the disease took place-he spent two years in Peru-and where it was passionately discussed. In addition, Townsend followed the infection with, and recovery from, Oroya fever and verruga peruana of a Briton who had assisted his experiments in the Andes.73 One reviewer from London's Tropical Diseases Bureau characterized Townsend's statements as "controversial", and another commented on the work of a Peruvian scientist in the following terms: "The author evidently does not accept the well-grounded conclusion of the expedition of the Harvard School of Tropical Medicine . . . Consequently it would tend to confusion to publish an abstract of his paper."74 The clinical and geographical evidence cited by Peruvians was not considered enough to defend the assumption that Oroya fever and verruga had a single cause. Many foreign scientists believed that the Peruvians had to conform to the normative rules of bacteriology in order to prove their clinical arguments. This was the beginning, or rather a continuation, of a controversy over Carrion's disease that could be settled once and for all only by isolating the causative microorganism of both infections and comparing their immune reactions. 69  Curiously, after the Strong expedition, Barton's findings of 1909 began to be accepted by Peruvian scientists. Local bacteriological research experimented with Bartonella bacillifornis under the assumption that it was the causative agent of both diseases. During more than a decade, however, these efforts proved fruitless. In 1924, a Peruvian bacteriologist reviewed the most important work that had attempted to obtain the Bartonella culture using Oroya fever and concluded: "Up to this point, all attempts to obtain the reproduction of the parasites outside the organism have been without results".75 When Peruvian researchers were unable to show that Bartonella played a role in verruga peruana, Hideyo Noguchi, a Japanese-American scientist working at the Rockefeller Institute for Medical Research, became deeply interested in the debate and gave what is considered today the solution to the riddle. Noguchi was an compulsive worker who was proud of obtaining results where nobody else could, on subjects ranging from snake venoms, syphilis, trachoma, poliomyelitis, and bartonellosis to yellow fever. Noguchi's first encounter with Carrion's disease took place in 1919 when he travelled from his laboratory in New York to Peru as part of a Rockefeller Foundation commission that was studying yellow fever. Over the next few years, Noguchi was able to obtain Peruvian materials on verruga and Oroya fever thanks to his association with Telemaco Battistini, a Peruvian student at the Rockefeller Institute. In addition, both Hercelles and Strong sent to Noguchi tissues from cases of Oroya fever and verruga.
With these materials Noguchi published in the mid-1920s a series of articles (some of them co-authored with Battistini) in which he described an artificial culture of Bartonella bacilliformis and the successful experimentation with animals. Noguchi found the characteristic bacilliform bodies present in the red cells, and cultivated a microorganism of similar appearance in 1925. The culture was inoculated into young monkeys and was found to be capable of inducing characteristic verruga peruana on the skin. Although these experiments already suggested that Oroya fever and verruga peruana were of common origin, it was also necessary to isolate the organism from human warts and test its behaviour on animals. Through the co-operation of Oswaldo Hercelles, then professor of bacteriology at San Marcos, nodules excised from two cases of verruga were secured for Noguchi early in 1926.76 From one of these, a culture was obtained which did not differ in any respect from that previously cultivated from the blood of the Oroya fever patient. This culture reproduced the characteristic Oroya fever as well as Peruvian wart in monkeys. Noguchi was able to recover the microorganism again from blood or warts of the inoculated animals. Those animals which did not succumb to the experimental infection recovered completely and became resistant to a second attempt to infect them.
Noguchi used this fact to explain the discrepancy between the result of Carrion's experiment and that of the Harvard Commission.77 According to Noguchi, Carri6n was susceptible to infection with bartonella, while the "volunteer" inoculated by the Harvard commission was resistant, probably because he had suffered from a earlier attack. Noguchi's achievement provided Peruvian scientists with the bacteriological proof they were lacking.78 As a result, the disease became internationally known as Carri6n's disease (although the term human bartonellosis is also used today), Carri6n's death appeared vindicated, and the local medical tradition reassured. Nevertheless, this was not the end of Strong's work in Peru. In 1936, on retiring from his professorship at Harvard, he decided to organize a new expedition to Peru to confirm or refute Noguchi's work. There was no institutional pressure to return to a topic then considered of secondary importance, especially for somebody who was already a leading figure in U.S. medicine. However, Strong knew that this was the last field expedition he would carry out and probably wanted to end his career by returning to the topic that had fascinated him during his first year at Harvard. The new expedition to Peru faced severe difficulties and had to be supported by a private fund and by monetary contributions from members of the party, who paid for their own personal and research expenses, which included the shipment from India to Peru of fifteen Rhesus monkeys.
No new discoveries occurred during Strong's 1937 expedition, which confirmed Noguchi's finding that Oroya fever and verruga peruana had the same causative microorganism.79 Strong was aware that nationalistic and scientific concerns were intertwined in the debate and tried to handle carefully the feelings of Peruvians. In a letter to a former officer of the Rockefeller Foundation Strong wrote: The Peruvian doctors regard the form of anemia we are going to study as rather a private affair since it is-not known to occur in any other country and our contacts will have to be made discreetly and diplomatically in order not to arouse any jealousy or antagonism. In fact, it is my plan to have at least one Peruvian physician associated with us in the work.80 It is significant that the final investigations on Carrion's disease were carried out either abroad or by foreigners. The increasingly important role played by U.S. researchers was partly an outcome of the limitations of Peruvian bacteriology, and especially of its inability to create a permanent and independent institutional basis.
The visit of Noguchi to Peru coincided with a reorganization of the Peruvian state that changed the institutional basis in which bacteriology emerged. A civilian dictator, the businessman Augusto B Leguia, initiated in 1919 an era of heavy spending on public works, favourable conditions for foreign investment in export-producing areas, and small regard for democratic expression. Assuming that local resources and personnel were insufficient and inadequate, Leguia delegated several of the state's responsibilities (like education, sanitation and technological improvements for agriculture) to U. new trend was clear when Leguia named two Americans in succession to direct the Direccion de Salubridad Publica. The Americans were followed by a Peruvian psychiatrist, Doctor Sebastian Lorente, committed to public hygiene, which he described as: "a science that is destined to do more good than all the other medical devices discovered or administered combined".81 Under Lorente's influence, Peruvian sanitation paid less attention to basic research, and fewer resources were allocated for the development of local scientific capabilities in bacteriology, which before the Leguia regime had been justified in terms of its potential benefit for public health. Leguia's emphasis on applied science increased routine work in the bacteriology laboratories because they were supported directly or indirectly by the State. The staff of the Instituto Municipal de Higiene of Lima, for example, became overloaded with routine tasks like the analysis of potable water and beverages, the extermination of rats, and the production of serums and vaccines. These duties were heavy because the city was growing rapidly while the staff and resources of the laboratory were diminishing. The reports of the directors of the Instituto Municipal during the 1920s and early 1930s complain of poor material facilities and the scanty and outdated materials for bacteriological research, all indicating this centre's decay.82 In the 1920s, there was less time and space for basic research because the romantic vision of the previous two decades that bacteriology alone would eradicate infectious disease seemed exaggerated. In Peru as elsewhere, serum and vaccine therapies, the great hopes of bacteriology of the late nineteenth century, were considered by many doctors a dead end.83 The first Peruvian bacteriologists linked their research to the fight against infectious and tropical diseases which drained resources from the country. By 1920, however, the campaign against endemic and epidemic conditions seemed to the Peruvian authorities to be a matter of money and technique, and that additional research was not necessary.
Carri6n's disease, which was the centre of attention of Peruvian bacteriologists, was a rural disease of secondary economic importance, endemic only in narrow Andean valleys where the majority of inhabitants had developed a natural immunity. It was well-known that one way to avoid the disease was to use a mosquito net or to prevent strangers from sleeping in areas where the vector existed, since it was a nocturnal insect. In addition, the census of 1940 found a curious polarized distribution of the Andean population, i.e. the majority of people lived below and above the endemic areas of verruga. These facts reduced the economic relevance of Barton's discovery and undermined Peruvian bacteriology's claim to utility.84 81 Sebastian Lorente, Nuestros problemas medico The young and dispersed group of bacteriologists was unable to respond effectively to the new challenges. The achievements of the earlier generation of Peruvian bacteriologists were more difficult to replicate and the work of foreign scientists ultimately surpassed local work.85 The decay of Peruvian bacteriology during the 1920s also resulted from local institutional weaknesses present from the very beginning. The different locations in which bacteriology was practised were not primarily dedicated to research, but rather to developing cures, educating physicians, and performing sanitary tasks.
Bacteriology was originally carried on in centres such as hospitals, the Instituto Municipal de Higiene and the Faculty of Medicine. Initially, institutional dispersion was beneficial because it generated competition to resolve the etiological question of Carrion's disease. But in another sense, it discouraged the consolidation of a scientific community because work tended to be duplicated, there was no uniformity in scientific apprenticeship, and resources were not centralized. Dispersion partly explains the lack of a more ambitious research programme. The search for one causative agent, the concentration on morphological description, and the lack of advanced local studies in entomology, all revealed the absence of higher goals in Peruvian bacteriology.
Peruvian bacteriology remained in decay until 1936, when Telemaco Battistini created the Instituto Nacional de Salud. A new generation of microbiologists, with few ties to past traditions and little knowledge of the development of their discipline, was formed here. This was the beginning of a new cycle of boom and bust similar to that which characterized the emergent period of Peruvian bacteriology.

Conclusion
Carrion's self-experimentation became a central ingredient in the Peruvian medical tradition and in the assumptions of Peruvian bacteriology. His experience reinforced the belief that there was a medical geography unique to the country that could be best understood by local practitioners and scientists. Initially, Barton's discovery of 1909 was not completely recognized, locally or internationally, until validated by the authoritative work and word of a Harvard scientist.86 However, other dimensions of Strong's work were disputed by Peruvian physicians with arguments that partly reflected their preference for clinical and geographical frameworks. The difficulties confronted by bacteriological research in Peru and even the perception of the success of Strong's expedition of 1913, suggest a more general process in which novel institutional structures and new knowledge in tropical medicine were attached to particular interests and validated by international networks, where scientists from cases of malaria. Andres Arana Sialer, Estadistica productivity declined, see Rebagliati, op. cit., note 27 hospitalaria, Lima, Imp. del Hospital Victor Larco above, pp. 191-204. Herrera, 1933, pp. 8, 10, 13, 16. In the 1940s, DDT 86 Bart6n's case resembles that of the Cuban Carlos controlled the sandfly and antibiotics treated the J Finlay, who presented a basically correct theory of anaemia produced by Oroya fever. the mosquito transmission of yellow fever in 1881, backward countries usually had little power and resources. This appears clear in Peru were science was carried out under adverse conditions such as a chronic lack of funds, scarce institutional continuity, irregular support from the state and changing public esteem. Partly because of this context, Peruvian bacteriologists had to be flexible, accommodating different and sometimes contradictory dimensions of the work of nationals and foreigners, and they resorted to both old medical traditions and new scientific paradigms. However, in this case, their efforts were insufficient to overcome the institutional and political obstacles that arrested the development of Peruvian bacteriology. Other Latin American examples, like the Instituto Oswaldo Cruz of Brasil, suggest that it was possible to sustain a balance between sanitary tasks and original basic research under adverse conditions.87 A final question is why Strong did not find a permanent academic niche for tropical medicine at Harvard? Strong's energy and reputation and the support of a prestigious academic institution and of Boston's elite were enough to launch tropical medicine as an independent academic entity in Boston but not to sustain it. Although this result might be related to the scientific expeditions that Strong organized after 1913 and to U.S. developments that I have not presented here, I will suggest two complementary answers to the question. First, tropical medicine in Boston never achieved a permanent alliance between local needs, the interests of the government or of the military, and the goals of private philanthropy. Second, the U.S. governments of the first decades of the twentieth century were reluctant to recognize that they played an imperial role in the independent republics of Latin America. This might have been a major difference between the U.S. and those European countries that defined and supported academic tropical medicine as a crucial component of their formal empires.