tu Z P-H u CM O tu tu O $ P-H nJ < Z O P-H Z THE NEW AGE OF HEALTH LABORATORIES 1885-1915 This booklet, as well as the exhibit to which it relates, was prepared by James H. Cassedy. The art work for both is by Daniel Carangi. The Pasteur and Goldberger manuscripts displayed in the exhibit are from the collections of the National Library of Medicine, as are virtually ail of the original monographs and reports and a major portion of the photographs. Acknowledgments: The Library is grateful to the archivai staff of the Institut Pasteur of Paris for searching for appropriate items, for providing copies of photographs, clippings, and other material, and for permitting their display. Thanks are extended to Dr. Ramunas Kondratas and Mr. Michael Harris of the Division of Médical Sciences, U.S. Muséum of American History, for helpful suggestions as well as the loan of a number of objects. Dr. Victoria Harden, Curator of the NIH Muséum of Médical Research, also kindly shared information and material. Jan Lazarus and Margaret Kaiser of NLM's History of Medicine Division expended large amounts of time and care in searching for and arranging for the duplication of materials for the exhibit. Helpful assistance was also extended within the Division by Margaret Donovan, Dorothy Hanks, and Peter Hirtle. THE NEW AGE OF HEALTH LABORATORIES 1885-1915 AN EXHIBIT MAY-OCTOBER 1987 Marking the Centennial of the Founding of The Pasteur Institute of Paris and The National Institutes of Health National Library of Medicine • Bethesda, Maryland 1987 U.S. Depanment of Health and Human Resources—Public Health Service—National Institutes of Health Single copies of this booklet are available without charge by writing: Chief, History of Medicine Division National Library of Medicine 8600 Rockville Pike Bethesda, Maryland 20894 The New Age of Health Laboratories 1885-1915 James H. Cassedy Germs and the Création of Laboratories The bacteriological discoveries of the late nineteenth century represented a quantum leap in man's knowledge about diseases and life processes. This outpouring of new knowledge stirred up unprecedented excite- ment and hope among physicians and the gênerai public alike. Scientists and health officiais, meanwhile, recognizing that this wave of discovery could well be only the beginning, took advantage of the enthusiasm to push for improved facilities in which to extend their searches for the causative factors of diseases and for improved means of preventing or controlling the diseases. The resuit was a remarkable world-wide efflorescence of health-related laboratories, large and small, many of them university-related or government- run, but others independent. Prior to 1880, research laboratories occupied highly anomalous positions in the médical world. Indeed, almost the only substantial health-related research establishments—one could not count most of the tiny médical school facilities for teaching elementary chemistry among them—were a small number of labor- atories devoted to the study of physiology. The whole idea of bacteriological research, in fact, remained highly controversial, opposed by sanitarians who were seeking to improve health through environmental measures as well as by skeptics who remembered the many earlier failures of science to prove the germ theory of disease. During the last rvvo décades of the nineteenth century, however, this opposition broke down before the cumulating weight of the new discoveries, and with it the importance of having good laboratory facilities for research was increasingly accepted. Among the projectors of the new laboratories were the earliest heralds and giants of the bacteriological âge themselves—individuals such as Louis Pasteur in France and Robert Koch in Germany, who had worked out their convincing early proofs of the germ theory of disease with only the barest of research facili- ties. More often the projectors were students and disciples of the first pioneers along with investigators who from a distance had followed the early reports in scientific joumals. Virtually ail, in any case, shaped institutions that were predominantly concerned, at least in their early décades, with hygiène, microbiology, and the infectious diseases of mankind. Relatively few of thèse new laboratories or institutes were devoted exclusively to research. In fact, scientists in some of them did practically none, but concerned themselves with such routine work as performing bacteriological diagnoses or producing and distributing vaccines or sera, both of which activities quickly became attractive sources of income. In many other laboratories, however, especially the larger establishments, research work was carried on along with one or more service activities. Pasteur and the Pasteur Institute, 1880-1915 Among the very first of the large health research institutes, and one that became a model for many others, was the institution built for and by Louis Pasteur in Paris. During the quarter-century prior to 1885, working much of the time in cramped laboratories at the Ecole Normale Supérieure of Paris, Pasteur had earned the admiration of scientists everywhere with his investigations into crystallography and spontaneous génération; his applied researches bearing on the produc- tion of béer and wine and on the cultivation of silkworms; and his studies of the etiology and prévention of such animal diseases as anthrax, fowl choiera, and s wine erysipelas. 2 Pasteurs early laboratory and animal cages at l'Ecole Normale 3 However, the great impetus to the création of a Pasteur Institute came from Pasteurs researches, late in his career, on rabies, culminating with the daring and successful inoculation in July 1885 of the Alsatian boy, Joseph Meister, against the disease. This initial inoculation almost immediately pre- cipitated a flood of rabies victims descending upon Pasteurs modest laboratory from ail over Europe and the Americas in hope of obtaining treatment. News of thèse dramatic human and scientific developments was spread far and wide by a remarkable outpouring of stories, both in the popular press and in médical publications. While some of the accounts, both in France and abroad, were critical of Pasteur and the early inoculation processes, many others recognized the break- through that Pasteur had achieved. Most Frenchmen, for their part, still smarting from their crushing military defeat in the Franco- Prussian War of 1870, welcomed the discovery as a major boost to their national morale and prestige. In the French Acade'mie des Sciences, Pasteurs friends quickly moved to create a French center for manufacturing the rabies vaccine and performing inoculations, an institution that would also include spacious facilities for Pasteurs researches. In 1886 a committee organized a public subscription which rapidly attracted funds from ail over France and many foreign countries. In 1887 a plot of land was purchased in Paris and construction on the first laboratory buildings was started. Finally, in late 1888, the Pasteur Institute was inaugurated in a ceremony attended by many scientists and dignitaries, headed by Mr. Sadi Camot, Président of France. By the time his new Institute was ready for occupancy, Pasteur was tired, aging, and impaired by a second stroke. In his own words, he was a man "vanquished by time." He managed to continue some of his researches on rabies and to défend his work against occasional detractors. However, much of his time was taken up with organizing the Institute and acknowledging the world's plaudits. He died in 1895 and was eventually interred in an impressive crypt on the grounds of the Institute. During the following years, up to World War I, the Pasteur Institute flourished in the aura of the great man's name while nurturing and expanding on the research Unes and interests he had started. Further physical growth quickly became necessary. Among the major early additions were the acquisition of extensive sérum production facilities in the Paris suburbs, the building of a separate chemistry building in 1901 and, about the same time, the development and completion of a research hospital of 120 beds, primarily for infectious disease studies. Meanwhile, continued scientific excellence was achieved, during that period and beyond, under two eminent directors, Emile Duclaux from 1895 to 1904 and Emile Roux from 1904 to 1933; both men had been close disciples and associâtes of Pasteur. Roux, along with Alexandre Yersin, Louis Martin, and other disciples, in the early 1890s made the Institute one of the chief centers of research on the etiology of diphtheria and of the intro- duction and production of antitoxin against that disease. And as time went by, the Institute's staff scientists launched equally important investigations of other diseases. Apart from the regular staff, from an early date distinguished outside scientists were invited to use the facilities. As early as 1888 Pasteur himself made room for the Russian scientist Elie Metchnikoff as a laboratory chief. Remaining in Paris up until his death in 1916, the latter found the Institute to be a congenial site for much of his research into the mechanisms of immunology. Similarly, other "independent spirits" of science were offered facilities, including men of the stature of the French 4 Emile Duclaux, Pasteurs successor as Director of the Pasteur Institute. Plan du Ier étage de l'Inftitut Pafteur en 1888. 5 Pasteur Institute. Layout of one floor A < r\ ■■ s • r • ■Mr>yA\Aisr kH/ ;i. Medallion struck for Pasteurs 70th birthday, 1892 5 An early inoculation of diphtheria antitoxin, 1895 Emile Roux, assisted by Drs. Laveran, Metchnikoff, and Yersin, with students of the Pasteur Institute's first microbiology course PREMIER COURS DE MICROBIE TECHNIQUE L'enseignement de mkrobie technique (microbio- logie) fut inauguré le 15 Mars 1889. Ce cours fut créé par le Docteur Roux avec Yersin comme préparateur. Ce cours de perfectionnement microbiologique a été complété par un enseignement sérologique. Il est suivi chaque cannée par une centaine d'étu- diants venant de France et du monde entier. («) $ @ $ 1 - THIROLOIX î - Dr BATTLE î - Dr ARCHINARD « - Dr RÉMOND 5 - Dr PRÉEL 6 . HALUON 7 - ETUNGER 8 - Dr LORIS MELIKOFF » ■ MARQUESY 10 • OUSTANIOL 11 - Dr LEVITSKY 12 • REPIN J - Dr LAVERAN 4 • Dr ROUX S - Dr METCHNIKOFF 6 ■ Dr YERSIN 7 - Dr SCHLEMMER 8 • Dr SUZANNE military physician Alphonse Laveran, who as early as 1880 had discovered the causative organism of malaria. The Pasteur Institute became, along with Koch's Institute in Berlin, one of the two principal early centers in the world for teaching the new techniques of microbiological research as well as for disseminating information about the modes of producing vaccines and sera. Formai classes in biochemistry (Duclaux) and microbiology (Roux) were begun early in 1889. They soon attracted students from numerous countries, while many other scientists came to the Institute for shorter periods of observation. At the same time, places as teaching or research assistants were found on the Institute staff for a succession of junior scientists, some of whom subsequently achieved great renown. Particularly prominent were several who ultimately left the parent Pasteur Institute to form or help staff similar labora- tories or Pasteur institutes in other cities, among them Jules Bordet in Brussels, Albert Calmette in Saigon and later Lille, Charles Nicolle in Tunis, and Alexandre Yersin in Nhatrang and Hanoi. Elsewhere, other important laboratories and health research institutes were being founded with the Pasteur Institute as a principal source of inspiration if not as an actual model. Among thèse, the Russian Institute for Expér- imental Medicine opened in St. Petersburg in 1890, the British Institute of Préventive Medicine (later changed to the Lister Institute) in 1891, and Shibasaburo Kitasato's Institute for Infectious Diseases in Japan in 1892. In Germany, meanwhile, Robert Koch had made his great bacteriological contributions of the 1880s in the laboratories of the Impérial Health Office and the University of Berlin. Only in 1891 did he finally obtain his own magnificent facilities, the Institut fur Infections- krankenheiten. Moreover, within a few years several of Koch's outstanding students and assistants had become heads of institutes, prominent among them Kitasato, Emil von Behring, and Paul Ehrlich. Robert Koch's Institut fur Infectionskrankenheiten in Berlin Americans and the Growth of Health Laboratories It is hardly surprising, given the country's historié lag in éducation, science, and other areas of leaming, that the United States failed to produce a Pasteur, Koch, Lister, or other giant figure in the early décades of the bac- teriological révolution. Nevertheless, many Americans were anxious to make up such deficiencies as rapidly as possible. Despite the well-entrenched anticontagionist beliefs that had prevailed hère throughout much of the nineteenth century, Americans proved as réceptive as individuals in other nations to the new discoveries. Since before the Civil War, American scientists who were accomplished in microscopy—Joseph Leidy, John Riddell, John C. Dalton, Jeffries Wyman, and others— had been viewing algae, infusoria, animalcules, and other minute organisms through high- powered lenses, but they lacked the techniques necessary either to cultivate such organisms in the laboratory or to connect them positively with given diseases. When the Europeans, during the 1870s and 1880s, began to publish their successes in thèse areas, a new génération of American physicians quickly demonstrated its eagemess to leam about and perhaps duplicate and extend those findings. A few of thèse individuals—notably George Stemberg and Theobald Smith—virtually taught them- selves the principles of bacteriology without leaving the United States, and then went on to make outstanding original contributions in the field. Others, however, in increasingly large numbers, opted to cross the Atlantic to meet the European investigators in their laboratories and to learn from them the exacting techniques of the new science. While some of them ultimately went to the British Institute and other laboratories as they were founded, for much of this pre-World War I period scientists of ail nations made the Koch and Pasteur laboratories their desti- nations of choice. German educational, scientific, and médical institutions, of course, were already at a high level of prestige worldwide. Now large additional numbers of Americans and other foreigners were attracted to Koch's laboratories, where they enrolled in courses of study or made arrangements to do research. Two of America's pioneer microbiologists: at left, William H. Park, N.Y. City Health Department; at right, Theobald Smith, U.S. Bureau of Animal Industry THE NEW YORK PASTEUR INSTITUTE BUILDING Where the Diphtheria Antitoxic Sérum and other Biological Products ai Prepared. (New York Biological and Vaccinal Institute.) One of several American sérum centers named after Pasteur 9 I III C'\RM(ilK L\HORAT()RY ■ ; ;• l..i-t Twcntv-sixth Si., New York This early New York laboratory was the gift of steel magnate Andrew Carnegie American awareness of and connections with Pasteur and his laboratories expanded greatly with the early 1880s, when reports in the periodical literature alerted the médical and scientific community to the progress of the rabies researches. Popular interest intensified somewhat later, in mid-1885, immediately following Pasteurs first human inoculation against rabies. Later the same year, the well- publicized trip to Paris of a group of Newark children to receive inoculations, a trip sponsored by the New York Herald, brought this enthusiasm to its peak. Beginning about this same time but continuing for over a décade, American physicians and health officers were drawn to Paris to observe Pasteurs methods of treating rabies and to bring back samples of the sérum used. A few Americans, during the mid-1880s, sent contributions of money for the Pasteur Institute building fund. And, after completion of the Institute, some Americans began enrolling in the courses conducted by Roux and Duclaux, while others came for varying periods of research on immunology or some particular disease organism. Besides the training they received in Europe, the Americans came back filled with ideas for their own new laboratories and research institutions. In several cities, groups drew up plans for American Pasteur institutes that were to be principally devoted to producing anti-rabies sérum, selling it, and administering it to patients; at least three such institutions were actually formed, in New York, Chicago, and Ann Arbor. Pharmaceutical firms also began expanding their laboratory facilities during this period in order to take advantage of the large new market for sera and vaccines. Much more important scientifically at this time, however, were the numerous research and public health laboratories that came into being. 10 Founders Hall, Rockefeller Institute for Médical Research, 1906 Several of the earliest laboratories were developed in or attached to académie insti- tutions. Following the création in 1884 of the pioneering Carnegie Laboratory at the Bellevue Hospital Médical Collège, substantial bacteri- ological or hygienic laboratories were founded at New York University (1886), the University of Michigan (1889), the University of Penn- sylvania (1889), and thejohns Hopkins Médical School (1893). Meanwhile, laboratories that were established between 1886 and 1893 by the Massachusetts State Board of Health and the health departments of Providence and New York City provided many of the earliest démonstrations of the significance of bacteriology for practical public health work. Thèse pioneer facilities were soon duplicated in other American universities and in other state and city health departments. Few if any, however, offered such rich opportunities for research as those provided at the Rockefeller Institute for Médical Research, founded in 1901. Certainly, when that Institute acquired its research hospital in 1910, it became the first of the American health-research institutes to match the Pasteur and Koch institutes at ail closely in size and scientific stature. Still another important source of research support and activity was the Fédéral govern- ment. Several différent govemmental agencies began, during the 1880s and 1890s, to establish health-related laboratories or to promote research. The short-lived National Board of Health had no laboratories of its own but did award funds for sanitary research. In the Department of Agriculture, the work of the 11 Iïi.- M.r.l l.nml. wlii. h in |<>00 1901. soh««lli |)l'f lh> <\jm iïiik-iiIs . and Dr I .m. -, ' '.iicmII. Leading participants in the Army's famous yellow fever experiments in Cuba Bureau of Chemistry, under Harvey Wiley, was mainly devoted to routine laboratory analyses, but the Bureau of Animal Industry provided scientists of the caliber of Theobald Smith, Daniel Salmon, and Emil A. de Schweinitz with excellent opportunities for original research. The Army Médical Muséum also took on a research mission. Its earliest facilities, modest though they were, nonetheless made possible much of the microbiological research of several outstanding investigators, notably Joseph J. Woodward and George M. Sternberg After 1893, however, the establishment of the Army Médical School and création of additional laboratories transformed the Muséum into an increasingly productive scientific institution, one which supported the bacteriological and parasitological research not only of Walter Reed but of a steadily growing coterie of other capable army médical scientists. 12 The Hygienic Laboratory The Hygienic Laboratory, forerunner of the présent National Institutes of Health, was among the very first of the American health laboratories to be established. However, for its first dozen or so years, it remained small and unpretentious. The facility was set up in 1887 in a single room of the United States Marine Hospital on Staten Island and was moved in 1891 to space in the headquarters building of the Marine Flospital Service, in Washington. The first Director of the Laboratory, Dr. Joseph J. Kinyoun, a recently appointed médical officer in the Service, had taken courses in bacteriology at New York's Carnegie Laboratory in 1885 under an excellent American preceptor, Herman Biggs, and he may also hâve had training in European laboratories about the same time. In any case, in order to make the Laboratory more effective, he made a number of trips during the 1890s to both the Koch and Pasteur institutes to study new bacteriological discoveries and techniques. During the early Kinyoun years the Hygienic Laboratory was literally a one-man opération. Even after 1890 it often had no more than one or two médical officers temporarily assigned at any one time to share the scientific work. Kinyoun himself became an excellent, if over- worked, laboratory diagnostician whose services were increasingly called upon by personnel at the various marine hospitals and quarantine stations. During the great choiera and yellow fever scares of the 1890s, he was from time to time pulled out of his laboratory for periods of spécial duty as quarantine inspector at New York or other ports. Never- theless, he found some time for research. He confirmed the etiology of choiera, anthrax, tuberculosis, and other diseases; he was one of the first in the United States to prépare and standardize diphtheria antitoxin; and he made exhaustive and important original studies Disinfection apparatus designed by Joseph Kinyoun, 1893-1894 M.iiii. H.i-ii.lnl lt>-|N>rt. I«'.H. 13 The first three directors of the Hygienic Laboratory: left to right, Joseph J. Kinyoun, Milton J. Rosenau, John F. Anderson Advisory Council, Hygienic Laboratory, May 1906, and personnel of the Hygienic Laboratory. lst ROW (left to right): Drs. John F. Urie, U.S. Navy; Milton J. Rosenau, Director, Hygienic Laboratory; William H. Weîch, Johns Hopkins University; Surgeon General Waïter Wyman; Drs. Victor C. Vaughan, University of Michigan; Frank E. Westbrook, University of Minnesota; A.D. Melvin, Chief, Bureau of Animal Industry, Department of Agriculture. 2nd ROW: Drs. William T. Sedgwick, Massachusetts Institute of Technology; Reid Hunt, Chief Division of Pharma- cology; John F. Anderson, Assistant Director, Hygienic Laboratory; Major Walter D. McCaw, U.S. Army; Drs. Charles Wardeïl Stiles, Chief, Division of Zoology; Joseph H. Kastle, Chief, Division of Chemistry; John W. Kerr. 3rd ROW: Laboratory Attendant William Lindgren; Stenographer E.B.K. Foltz; Clerk David G. Willets; Pharmacist F.J. Herty; Dr. Joseph Goldberger. 14 of the germicidal effect of various disinfectants, as well as developing equipment for the large-scale disinfection opérations of the Marine Hospital Service. However, it remained for others to build up the tiny Hygienic Laboratory into a first- class health research establishment. Kinyoun's successor, Milton J. Rosenau, accomplished much of this transformation during his ten years as Director, from 1899-1909, while John F. Anderson continued the process dunng the years up to 1915. Among the key initial steps taken were the création of separate divisions of chemistry, zoology, bacteriology and pathology, and pharmacology; the recruiting of able scientists to staff them; and the naming of a high-caliber advisory council under William H. Welch. Another important initiative was the launching by Rosenau in 1902 of a course of instruction in pathology and bacteriology for médical officers of the now-renamed Public Health and Marine Hospital Service. That course served the immédiate added function of providing the Hygienic Laboratory's permanent scientific staff with compétent assistants and even collaborators, sometimes for extended periods. It also served as a direct impetus for the création and staffing of laboratories in the various hospitals operated by the Service around the United States. Some of thèse quickly proved their value both in initiating occasional independent local investigations and in facilitating and assisting studies organized by scientists of the laboratory in Washington. Beginning in 1902, Congress assigned the Laboratory the large new function of testing and regulating ail vaccines and other biological products sold in interstate commerce, in- cluding inspection of the laboratories that manufactured them. At that time three such products—diphtheria and tetanus antitoxins and smallpox vaccine—were on the market. This testing work, together with the other new activities and enlarged staff, made an increase of space imperative. Congress finally recognized this need and authorized a new building specifically for the Laboratory. Completed in 1902, the structure still did not include space for some essential work, and it continued for some time to lack such key éléments as a research hospital and an adéquate animal facility. Nevertheless, with its added resources, the new building did constitute a large step toward achieving research respecta- bility, toward the attainment of the standard established by the Pasteur Institute for twentieth century health laboratories. The Hygienic Laboratory's extensive pre- World War I growth coincided with the period of American history often known as the Progressive era. In fact, the very existence of the Laboratory, as well as its lines of work, rellected many of the dominant beliefs, values, and objectives of that era: the expansion of government authority and activity generally; the reining in and régulation of big business; a new insistence on efficiency, expertise, and scientific knowledge in society and govern- ment; the conservation of ail of the nation's valuable resources—not only its forests and minerais but its human health, vitality, and well-being. A large proportion of the Laboratory staffs time and énergies, therefore, went into applied researches of immédiate relevance to given sanitary or public health concems. Many of thèse activities involved long-term field work, for which the laboratories and personnel of marine hospitals or quarantine stations often provided routine servicing though the central Laboratory remained as the backup and coordinating facility. Among the earliest of thèse studies, and one which attracted enormous public as well as scientific interest, was the investigation of Charles Wardeïl Stiles, Chief of the Laboratory's Division of Zoology, into the etiology and distribution of hookworm disease. Stiles determined, among other things, that this condition was endémie throughout many areas of the South, and as such was a primary factor in the chronic backwardness and desti- \.\\ Kit 11. ï'rmn Our O:.-»» ("<>,n cxpin/rit nt W-iuvctON (O ('.)—Mon c> whlcb bave the "- .-.:>>. .; i.m a plg* with (ht di|i i'ik nu aud rab- if. »nh rypbon! tevpr- ih«>c- are «toi » of the ibiu<; to be ■«n lu I,,- ^rtat eipeiimeut «talion whlcb l'ncle Sun. ha* establlsht il on the ban kg of th.- Potomac to ke*p d^<-«f< a»a> from his ihildien M il now ten years .-inc* , mit louai bureau of public b^alth wa* fo nded Tin Institution ha* pro<. i to be of enormous value, and there Il a posslbllity that It wlll some day be «uade a Cabinet departmeni with a secreur\ at its head. An >t Ih mi», the bureau lu controlled by tb< Secretary o: the Treasury. Its super in tendent Is Surveyor-On- •rai Wynian. whose lire bas been spent in figbfinK the gréât diseases which affeci tl» nation. It I* to him lhat we owe th< n.ovement now being made agnin.st fil>. rculohiK, pellagra and typhold fever, the govern- nwn' régulations ac to the «aie of viruses and toxlns, and also the establishment of the !: Its appropriations from Congre**. H Is conneeted with the national bureau of health. and it has so growu that It tM now one of the moM important of the gim minent undertakings. The hygienic laboratory' «onsists of several large buildings whlcb are devoted to research work. It con- ! Ui ii «lienilcal and other laboratories specially fitted up rooms In which ■-:< rms and microbes of ail klnds are reared, roome for the testing of die.iM through a 'indy of animal* which hâve bem infocted with them .md al) 'lie maeblnery for modem médical iuvestiga- >ion. It would ttikc mam colurans to glve a record of the Tarions kinds of work now going on and a descrip- tion of what has already bee-i accomplished In this Setter I can mention oui y a U w of the problems whleh are now being studled and some of the méthode by which the scientists arrive at their conclusions. Uncle Sam's Médical Zoo. One of the interesting features of the laboratory is Its stiuiv of human dise '-«s through animais of one kind or other. Indeed, in one respect the in.-'itution might be called "Uncle Sam's Médical Zoo," for it has colonies of animais which tbe governmenf keeps on band in order that it may imestigate through them the In the Guinea Pig Pens tn another part of tblfi f-in.«.- bouse is "i ..• I ,, ,,: cill iho gtiinoa-pig stock yards. This n. •!■],,|.o , ,i ,,f nnim littk in tis occupie. it» ,,*,, place In the research work, and many of those which hâve Iiihtî kept hère hâve been of -<-rvloe in tbe ► le- able dlscoTer»-"- made by this laboratory as to nnman diseases AH of thèse animais are carefi lly trrated. They hâve well ventilated honses beated by steam, and the best of food that can be obtalnod During my ht;iy I saw them feeding tbe monkeys The little animais were given bananas, bread, nuts and Much other thlngs as they specially like The guinea pigs are kept fat on gtiinea-plg dainties and the rabbits rejoue In greep let- tuce and cabbage. The animais are kept in perfec» health and as far as possible In good «plrlts In order that <*£ diseases given to them may be Ircetlv diag- nosed jid studled. 1911 press account of the work of the Hygienic Laboratory 16 tution of the "poor white" population. The American press prompdy hailed the discovery of what it termed the "germ of laziness." And, within a few years, Stiles's research per- suaded John D. Rockefeller to finance a massive hookworm eradication program through the South. Under Rosenau, Stiles, and the other Division chiefs, the Hygienic Laboratory within a few years was following the Pasteur and Koch institutes, albeit on a smaller scale, as a training ground for a new génération of biomédical researchers some of whom eventually achieved outstanding scientific réputations of their own. Prominent among such individuals was Joseph Goldberger. Goldberger spent nearly five years as an understudy of Stiles and several more years in Rosenau's laboratory, an accumulation of expérience that by 1910 had helped him gain independent récognition for studies in several areas of microbiology and parasitology. His great contribution, however, was as Chief of the Laboratory's large- scale pellagra investigation between 1914 and his death in 1929, a meticulous study in which he was able to establish definite links between pellagra and inadéquate diet. Pellagra and hookworm. to be sure, were only two of the diseases in connection with which the Hygienic Laboratory scientists of this period made outstanding contributions. Begining soon after 1900, extensive laboratory and field studies were launched of typhoid fever, yellow fever, plague, diphtheria, tularemia, and Rocky Mountain Spotted Fever, to name only some of the most prominent. In addition, Laboratory scientists were occasionally able to carry on long-term investigations of certain of the fundamental disease processes. Among the most significant of thèse was the work of Rosenau, Anderson, and Wade H. Frost on the problem of anaphylaxis, the allergie reaction experienced by some individuals to diphtheria antitoxin or other immunizing serums. By the outbreak of World War I, the Lab- oratory's facilities had not yet attracted foreign observers or students the way the Pasteur and Koch institutes did. Nevertheless, the work of its scientists was bringing distinction to the American government and people. More important, the work was establishing a solid base for the continued development of the Hygienic Laboratory and for its ultimate expansion into the National Institutes of Health. Suggestions for Further Reading Blake, John B., "Scientific Institutions since the Renaissance, their Rôle in Médical Research," Proceedings of the American Philosophical Society (Feb. 1957) Clark, Paul, Pioneer Microbiologists of America (1961) Dubos, René, Louis Pasteur, Free Lance of Science (1950) Foster, W.D., A History oj Médical Bacteriology and Immunology (1970) Furman, Bess, A Profile ofthe United States Public Health Service, 1798-1948 (1973) Harden, Victoria, înventing the N.I.H. (1986) Institut Pasteur (1938) Shryock, Richard H., American Médical Research (1947) Stimson, A.M., Bacteriological Investigations of the United States Public Health Service (1938) Williams, Ralph C, The United States Public Health Service, 1798-1950 (1951) 17 00 HYGIENIC LABORATORY.—BULLETIN No. 95 AUGTJST, 1914 LABORATORY STUDIES ON TETANUS I. Conditions Surround ing Tetanus Spores Artificially Implanted Into Vaccine Virus Jhe Behavior of Tetanus Spores Injected Subcut»/ yieously Into Guinea Pigs and White Mice vcellaneous Observations Upon Tetanus i ^ < ^o- V ** G*. ** *C **$, k\c ^ VWARD FRANCIS .^ *v >' N*" °e*. A*f/., •fJV |CV w ^ V # ^47^ °o%. •^ ,so 1** ;.\' ^ s\^ QV ; V ^ //. ^/ r*ù Z. > ^v ^V>«_ * /e r75<;> w .^w ■V'' c*' nN r>v

V V *** &Pr' The variety of research performed by Hygienic Laboratory scientists during the early décades is illustrated by the various reports published in the Laboratory's growing séries of scientific Bulletins, beginning in 1901. Rocky Mountain Laboratory, Hamilton, Montana, 1910. Temporary site of the Hygienic Laboratory's early studies of Rocky Mountain spotted fever. Front cover illustrations: Top: L'Institut Pasteur, Paris Artist's rendering, ca. 1889 Bottom: U.S. Hygienic Laboratory Washington, ca. 1910 Back cover illustration: Zeiss microscope purchased 1887 for the United States Hygienic Laboratory and used by the Laboratory's first Director, Dr. Joseph J. Kinyoun. U.S. Department of Health and Human Resources—Public Health Service—National Institutes of Health