• Nationality American

• Alma mater Cornell University, Albany Medical College

• Known for Texas cattle fever, Salmonella

• Scientific career : Fields : Epidemiology

• Institutions : US Department of Agriculture, Harvard University, Rockefeller University

Prof Theobald Smith FRS(For)^[1] HFRSE (July 31, 1859 – December 10, 1934) was a pioneering epidemiologist, bacteriologist, pathologist and professor. He is widely considered to be America's first internationally significant medical research scientist.^[2][3] His work included the study of Texas cattle fever and the epidemiology of cattle infected by ticks transmitting protozoa. He also discovered a species of Salmonella, named for his chief Daniel E. Salmon, and studied anaphylaxis, then referred to as Theobald Smith phenomenon.^[4] Smith taught at Columbian University (now George Washington University) and established the school's department of bacteriology, the first at a medical school in the United States.^[4] He also worked at Harvard University and the Rockefeller Institute.

Education

Smith was born in Albany, New York, the son of Philip Smith and his wife, Theresa Kexel.^[5]

He received a Bachelor of Philosophy degree from Cornell University in 1881, followed by an MD from Albany Medical College in 1883.^[2] After his graduation from medical school, Smith held a variety of temporary positions which might broadly be considered under the modern heading of "medical laboratory technician". After some prodding by his former professors, Smith secured a new research lab assistant position with the Veterinary Division of the US Department of Agriculture (USDA) in Washington, D.C., beginning his position there in December 1883.^[6]

Research

Smith became the Inspector of the newly created Bureau of Animal Industry (BAI) in 1884. Established by Congress to combat a wide range of animal diseases—from infectious disease of swine to bovine pneumonia, Texas cattle fever to glanders—Smith worked under Daniel E. Salmon, a veterinarian and Chief of the BAI.^[7] Smith also discovered the bacterial species which would eventually form the genus Salmonella. After two years of work studying the efficacy of bacterial vaccination in pigs, Smith erroneously believed he had found the causative agent of hog cholera.^[8]

Smith turned his attention to Texas fever, a debilitating cattle disease; this work is detailed in a chapter in Microbe Hunters, by Paul De Kruif. In 1889, he along with the veterinarian F.L. Kilbourne discovered Babesia bigemina, the tick-borne protozoan parasite responsible for Texas fever. This marked the first time that an arthropod had been definitively linked with the transmission of an infectious disease and presaged the eventual discovery of insects as important vectors in a number of diseases (see yellow fever, malaria).

Smith also taught at Columbian University in Washington, D.C. (now George Washington University) from 1886 to 1895, establishing the school's Department of Bacteriology. In 1887, Smith began research on water sanitation in his spare time, investigating the level of fecal coliform contamination in the Potomac River. Over the next five years, Smith expanded his studies to include the Hudson River and its tributaries.^[9]

While Smith's work at the BAI had been highly productive, he chafed against the federal government bureaucracy and the lack of leadership from his supervisor. In 1895 Smith moved to Cambridge, Massachusetts to accept a dual appointment: serve as professor of comparative pathology at Harvard University, and direct the pathology lab at the Massachusetts State Board of Health.^[6]

Smith joined the Rockefeller Institute for Medical Research as Director of the Department of Animal Pathology in 1915 and remained there until his retirement in 1929.

In 1933, Smith was awarded the Royal Society's prestigious Copley Medal "For his original research and observation on diseases of animals and man.".

Publications

• Parasitism and Disease (1934)

Other discoveries

• Observed differences between human and bovine tuberculosis (1895).

• Discussed the possibility of mosquitos as a malaria transmission vector (1899).

• Variation and bacterial pathogenesis (1900).

• Discovered anaphylaxis (1903), which is also sometimes referred to as "Theobald Smith's phenomenon".^[10]

• Brucellosis infections

• Used toxin/antitoxin as a vaccine for diphtheria (1909).

• In the process of investigating an epidemic of infectious abortions of cattle in 1919, Smith described the bacteria responsible for fetal membrane disease in cows now known as Campylobacter fetus.^[11]

References

• ^ Nuttall, G. H. F. (1935). "Theobald Smith. 1859-1934". Obituary Notices of Fellows of the Royal Society. 1 (4): 514–521. Bibcode:1935SciMo..40..196W. doi:10.1098/rsbm.1935.0014. JSTOR 768981.

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• ^{a b} Dolman, C.E.; Wolfe, R.J. (2003). Suppressing the Diseases of Animals and Man: Theobald Smith, Microbiologist. Boston Medical Library. ISBN 0-674-01220-8.

• ^ Middleton, James (July 1914). "A Great American Scientist: Dr. Theobald Smith, Head of The New Department Of Animal Diseases At The Rockefeller Institute". The World's Work: A History of Our Time. Doubleday, Page & Co. XLIV (2): 299–302. Retrieved 2009-08-04.

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• ^{a b} "1869 - 1930 - Cornell DU Alumni". cornelldu.org. Retrieved 2018-04-18.

• ^ Biographical Index of Former Fellows of the Royal Society of Edinburgh 1783–2002 (PDF). The Royal Society of Edinburgh. July 2006. ISBN 0-902-198-84-X.

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• ^{a b} Kruif, Paul De (2002) [1926]. Microbe Hunters. Harvest Books. ISBN 0-15-602777-1.

• ^ J.H., Brown (1 July 1935). "Theobald Smith 1859-1934". J Bacteriol. 30 (1): 196. Bibcode:1935SciMo..40..196W. doi:10.1128/JB.30.1.1-3.1935. PMC 543631. PMID 16559815.

• ^ "Theobald Smith, 1859-1934: A Fiftieth Anniversary Tribute"(PDF). ASM News. 50: 577–80. 1984. Archived from the original(PDF) on 2004-09-07.

• ^ T., Smith (1893). "A new method for determining quantitatively the pollution of water by fecal bacteria". 13th Annual Report of the State Board of Health of New York for 1892: 712–22.

• ^ "Whonamedit - dictionary of medical eponyms". whonamedit.com. Retrieved 2018-04-18.

• ^ Smith, T.; Taylor, M.S. (1919). "Some morphological and biological characters of the Spirilla (Vibrio fetus, n. sp.) associated with the disease of the fetal membranes in cattle". J Exp Med. 30 (4): 299–311. doi:10.1084/jem.30.4.299. PMC 2126685. PMID 19868360.

External links

• Paul de Kruif Microbe Hunters (Blue Ribbon Books) Harcourt Brace & Company Inc., New York 1926: ch. VIII Theobald Smith: Ticks and Texas Fever (pp. 234-251)

[...] The scope and thoroughness of Smith’s researches in bacteriology, immunology, and parasitology produced many discoveries of theoretical import and immediate utility to public health and veterinary medicine. He was the most distinguished early American microbiologist and probably the leading comparative pathologist in the world. His greatest accomplishment—elucidation of the causal agent and mode of transmission of Texas cattle fever—first conclusively proved that an infectious disease could be arthropod-borne. Unlike many contemporary bacteriologists in the United States, he received no training in France or Germany.

Smith’s parents were Philipp Schmitt, a tailor and the son of a farmer, and Theresia Kexel, whose recent forebears were village schoolmasters. Both born in Nassau, Germany, they married in 1854 and emigrated to America, settling in Albany, N.Y., where Philipp followed his trade for more than forty years. They took in boarders, worked hard, and were very thrifty. Their second child and only son was baptized in his mother’s Roman Catholic faith (the father being Lutheran) and given the surname of his godparent, Jacob Theobald, a friendly immigrant neighbor. He appears in the parish register as Theobald Schmitt but in high school lists as Theobald J, Smith, for he temporarily adopted his godfather’s first name, Before entering Cornell University, he discarded the second initial and rejected the Roman church.

At home, German was spoken, and Smith’s education began at a German-speaking private academy. As a youth he quoted Goethe, enjoyed Schiller, and subsequently mastered the original reports of Robert Koch and Paul Ehrlich. In 1872, after two years of parish schooling, he entered the recently founded Albany Free Academy, where he excelled in all subjects, became president of the debating society, and was valedictorian in 1876. With a state scholarship supplementing his earnings from piano lessons, organ-playing, and book keeping, he entered Cornell in 1877, His industry, versatility, and inclination for scientific studies brought durable friendships with the physiologist and comparative anatomist Burt G. Wilder and with the microscopist Simon H. Gage. In 1881 he received the Ph.B. degree with honors and enrolled at the Albany Medical College, where he headed the 1883 M.D. class. His thesis was entitled “Relations Between Cell-activity in Health and Disease.”

Smith felt unready for private practice. With Gage’s help he obtained an assistantship with Daniel E. Salmon, chief of the veterinary division of the U.S. Department of Agriculture, commencing December 1883. Six months later he became inspector in the new Bureau of Animal Industry, established by Congress under Salmon’s charge to combat bovine pleuropneumonia, glanders infectious diseases of swine, and Texas cattle fever. Smith taught himself Koch’s culture-plate methods and improved on them. Through careful field and laboratory studies of swine epizootics, he differentiated hog cholera from the multiplex swine plague (Schweineseuche), implicating distinctive bacillary species for each disease. These findings appeared in the annual reports of the Bureau from 1885 to 1895 and in two monographs, Hog Cholera: Its History, Nature and Treatment (1889) and Special Report on the Cause and Prevention of Swine Plague (1891). In 1886 pioneer observations involving hog cholera bacilli were made by Smith on bacterial variation—a phenomenon that excited his continuing speculative interest—and on the immunity developed by pigeons inoculated with heat-killed cultures, thus heralding a new approach to bacterial vaccine production. Salmon’s assumption of sole or senior authorship of several reports on this bacillus led to the selection of the species in 1900 as the prototype of an eponymous Salmonel la genus. Some twenty years after Smith discovered Salmonella choleraesuis, however, the actual etiological agent of hog cholera proved to be viral, and the bacillus was accepted thereafter as a secondary invader.

These projects overlapped with another major assignment. Texas cattle fever, on which Smith worked intermittently, restricted by its summer incidence. In November 1892, more than six years after first observing “small round bodies” in red blood corpuscles from stricken cattle, he completed his classic monograph Investigations Into the Nature, Causation, and Prevention of Texas or Southern Cattle Fever (1893), He found that the disease resulted from erythrocyte destruction by a protozoan microparasite, Pyrosoma bigeminum, carried in the blood of apparently healthy southern cattle and transmitted to susceptible northern cattle by the progeny of blood-sucking ticks (Boophilus bovis). The complex, meticulously verified tick-borne mechanism was viewed incredulously by many, but never refuted—a situation that facilitated acceptance within a decade of the mosquito-borne nature of malaria and yellow fever.

Smith’s international recognition was hastened by his publications in German journals. In Washington he was promoted in 1891 to chief of the division of animal pathology of the Bureau of Animal Industry, but Salmon sought unduly to divert credit for Smith’s work to himself and to other veterinarians. For example, F. L. Kilborne, superintendent of the experimental farm, was over generously made coauthor of the Texas fever monograph. Smith chafed under the repeated injustices but delayed resigning because of fresh research opportunities, including a novel protozoal disease of turkeys, and observations on two varieties of tubercle bacilli from mammals, which presaged a lifelong involvement with human and animal tuberculosis. Moreover, he had developed other interests, including the bacteriology of water supplies. Beginning in 1885 – 1886 with unofficial observations on the total bacterial count of samples from the Potomac River, he systematically examined (1892) microflora in the Hudson River for fecal bacteria. In a report to the New York Department of Health (1893), he advocated quantitative assays of Bacillus coli communis as an index of intestinal pollution and introduced the fermentation tube to demonstrate the presence of gas-producing coliforms. His techniques and detailed studies of B. coli and related microorganisms were incorporated in recommendations of the committee of American bacteriologists appointed in 1895 (on which Smith served under W. H. Welch’s chairmanship) that culminated in the first edition of the Standard Methods of Water Analysis (1905) of the American Public Health Association.

Smith recognized that improved sanitation of sewage, milk, and water supplies required an aroused public interest. He disliked the limelight but nevertheless addressed farmers and sanitarians and regularly participated in meetings of the Biological Society of Washington. In 1886 he became lecturer and professor of bacteriology at the National Medical College (the medical department of Columbian University, now known as George Washington University). This appointment, one of the first chairs of bacteriology at an American medical school, was held until 1895. His industry was leavened and his dissatisfactions eased by a happy marriage in 1888 to Lilian Hillyer Egleston, a clergyman’s daughter. Her intelligence, high principles, and social graces furthered her husband’s work and life aims. They had two daughters (born in Washington) and a son.

In 1895 Smith resigned from the Bureau, becoming director of an antitoxin laboratory for the Massachusetts State Board of Health and professor of zoology at Harvard University. In six months, in improvised quarters at the Bussey Institution in Jamaica Plain, near Boston, he produced potent diphtheria antitoxin. Through a cooperative arrangement devised by H. P. Walcott, chairman of the State Board of Health, and President Charles Eliot of Harvard, both of whom admired Smith, he was appointed in 1896 to the new George F. Fabyan chair of comparative pathology, endowed by a wealthy Bostonian. Smith retained his directorship of the antitoxin laboratory and was privileged to reside in a mansion nearby, commuting daily to Harvard Medical School. Although he took teaching and committee duties seriously, his class lectures were more thorough than inspiring. The dual position intensified his resolute pursuit of new knowledge on the etiology, pathology, and prevention of communicable disease.

During a European trip in 1896, Smith met many leading microbiologists, including Ehrlich and Koch. To the latter he imparted preliminary observations on two varieties of mammalian tubercle bacilli, which he expanded in another classic report, “A Comparative Study of Bovine Tubercle Bacilli and of Human Bacilli From Sputum” (1898). Three years later Koch confirmed these distinctions but failed to acknowledge Smith’s priority until 1908. Koch’s extreme views on the negligible role of bovine bacilli in human tuberculosis were not endorsed by Smith.

In 1903 Smith inspected several European vaccine lymph manufacturing facilities, prior to designing an enlarged antitoxin and vaccine laboratory, erected in 1904. Smith was the first scientist in North America to adopt Ehrlich’s standardized antitoxic unit; and he introduced many improvements in titration methods, which Ehrlich praised on visiting his laboratory in 1904. Irregularities in guinea pig susceptibility to toxin could be reduced through careful breeding and selection of animals (1905), especially by eliminating passively immune progeny of females previously used for titrations (1907). In studying the antigenic properties of toxin-antitoxin mixtures. Smith foresaw their application to the active immunization of humans (1909, 1910). Incidentally, he mentioned to Ehrlich his observation of the sudden death of guinea pigs following second injections of antitoxin. Ehrlich’s colleague R. Otto verified this serum-hypersensitivity, designating it the “Theobald Smith phenomenon” (1906).

In 1903 Smith and A. L. Reagh reported agglutination relationships between certain members of the typhoid-paratyphoid-coliform group of bacilli. A second paper, again involving the hog-cholera bacillus, revealed the nonidentity of its flagellar and somatic agglutinogens. These immunologic contributions were fundamental to subsequent development of the Kauffmann-White schema for identifying Salmonella organisms serologically.

Research opportunities in parasitology were plentiful. Malaria was endemic in parts of Massachusetts, and as early as 1896 Smith conjectured that the disease was mosquito-borne. The reluctance of the State Board of Health to support his hypothesis, and difficulties in studying malaria in an unfavorable latitude, discouraged him from this field and the palm soon went to Ronald Ross. Other parasitic diseases studied by Smith were murine sarcosporidiosis (1901), coccidiosis of mouse kidney (1902) and rabbit intestine (1910), and amebiasis in the pig (1910). In 1913 he revived investigations into turkey blackhead begun twenty years earlier in Washington.

The output and functions of the pioneer state laboratory multiplied, and administrative duties mounted. Smith was consulted by bacteriologists, veterinarians, and sanitarians; and Eliot encouraged his defense of animal experimentation during an antivivisectionist campaign (1902), his membership on the Charles River Dam committee (1903), and his inquiry into possible damage to animals by smelter smoke from the Anaconda Copper Mining Company in Montana (1906). Before retiring from the presidency of Harvard University in 1909. Eliot persuaded Smith to give eight Lowell lectures (never published) to popularize comparative pathology. In 1912, as Harvard exchange professor at the University of Berlin, Smith took his family to Germany for six months. His inaugural address, “Parasitismus und Krankheit,” abstractly developed the theme of his Harvey lecture (1906) on the parasitism of the tubercle bacillus. His convictions about the importance of comparative pathology were permeated increasingly by the concept of host-parasite interrelationships.

Smith’s acknowledged leadership in this field and his unmatched reputation for productive research led early in 1914 to an invitation from [Dr. Simon Flexner (born 1863)], director of the Rockefeller Institute for Medical Research, to head the newly endowed department of animal pathology to be established at Princeton, N.J. (In 1901, at the inception of the Institute, he had rejected an offer to become its director but had agreed to join the board of scientific directors under Welch’s chairmanship.) Although fifty-five years old and not in robust health, Smith resigned from the State Board of Health that summer, but remained at Harvard for a year until preliminaries for the new department had been fulfilled. At a testimonial dinner in June 1915 extraordinary tributes were paid to Smith by distinguished colleagues from all over the world.

For more than two years after this move, Smith was largely responsible, in consultation with Rockefeller Instituterepresentatives,for the general plans of the new division, design of laboratories and animal quarters, and selection of equipment. By the end of 1917 antipneumococcus and antimeningococcus sera were being manufactured in horses, researches into cattle diseases had begun, and a commodious director’s house was under construction. In 1920 Smith and H .W. Graybill showed that the protozoon causing turkey blackhead was transmitted in novel fashion, involving ingestion by the healthy host of the embryonated eggs of a small nematode, Heterakis papillosa, which was parasitic in the ceca of infected birds. (The infective agent, erroneously designated Amoeba meleagridis by Smith many years before, was recognized by E. E. Tyzzer, his successor at Harvard, as a unique flagellate, which he renamed Histomonas meleagridis.) Proximity to a large dairy herd infected with Bang’s disease reawakened Smith’s early interest in Bacillus abortus and bovine contagious abortion; and he published, sometimes with R. B. Little, twelve papers and a monograph in this field. In 1926 they described the protection induced by vaccinating heifers with living B. abortus culture of low virulence. Other investigations concerned Vibrio fetus,a spirillar cause of cattle abortion, hitherto unrecognized in America; a possible new species, Bacillus actinoides, producing bronchopneumonia in calves;tne vitally protective antibodies in colostrum for newborn calves; and the pathogenicity of certain bovine strains of B, coli in calves deprived of colostrum.

In 1929, at age seventy, Smith relinquished his directorship of the division of animal pathology and was succeeded by Carl Ten Broeck, a longtime associate. He continued working at Princeton as member emeritus of the Rockefeller Institute. Smith had become vice-president of the board of scientific directors in 1924 and succeeded Welch as president in 1933. In November 1934 increasing weakness forced his hospitalization in New York, where he died just before an exploratory operation for intestinal cancer. His ashes and, six years later, those of his wife were buried in the woods at their summer home at Silver Lake, New Hampshire. In 1967 they were reinterred in the nearby Chocorua cemetery.

Honors came to Smith rather late in life. Between 1917 and 1933 he delivered the Herter, Mellon, Pasteur, Gross, De Lamar, Milbank Memorial, Welch, and Thayer lectures. A climactic series of five Vanuxem lectures, given at Princeton in 1933, and published in book form as Parasitism and Disease (1934), philosophically embodied his scientific credo. He received a dozen honorary doctorates from renowned American and European universities. He held membership in numerous scientific and medical societies, and was president of the Society of American Bacteriologists (1903), the National Tuberculosis Association (1926), and the Triennial Congress of Physicians and Surgeons (1928). He was elected a trustee of the Carnegie Institution in 1917. Smith was a foreign member of the Royal Society of London and eleven other ancient societies. Further honor awards were the Mary Kingsley, Flattery, Kober, Trudeau, Holland, Sedgwick, Manson, and Copley medals. Recommended several times for the Nobel prize, this ultimate distinction eluded him, although he surely deserved it. His portrait in oils is at the entrance to the Theobald Smith Building of the Rockefeller Institute, now known as the Rockefeller University, which he served so faithfully in various capacities for thirty-three years.

Smith unpretentiously summarized his own life work as “a study of the causes of infectious diseases and a search for their control.” His outstanding success in this quest derived from a farsighted, dispassionately critical intelligence, linked to capacities for unsparing industry, punctilious concern for detail, technical inventiveness, and indomitable persistence. These qualities were applied to realistically chosen problems. Between 1883 and 1934 he published at least one scientific research report annually, and in several of these years the annual output was ten or more such publications–a record demanding rare degrees of self-discipline and dedication to the work ethic. As a director he was fair in judgment but sparing of praise, painstakingly conscientious, and abhorrent of waste or extravagance. All who knew Smith and his work respected him. Individuals as diverseas Osler, Welch, Simon Flexner, Prudden, Rous, [Dr. Richard Edwin Shope (born 1901)], and Ten Broeck held him in profound admiration. Smith was too reticent to be popular, and he displayed an element of restraint even with Gage, despite their half-century of close friendship. Hans Zinsser observes, “there was about him an unobtrusive pride, a reserve tinged with austerity which did not invite easy intimacy.”

Smith’s relaxations were modest and quiet, befitting his nature. When tired, he sought solace in reading, piano-playing, or calculus. During the hot summer months, he found refreshment at his lakeside home, where besides preparing manuscripts, he enjoyed boating, making household repairs, and landscaping. His pattern of life was consistently rational, yet he did not lack emotion. He hated war and wastefulness, for example, but knew that great ideas must be both launched and defended, often at high cost in a hostile environment. That a scientist of such unswerving probity and fine accomplishments should carry so little fame among his countrymen testifies partly to his self-effacing character. Many of his discriminating contemporaries thought him comparable to Pasteur and Koch, and the passage of time has not dimmed the luster of his contributions to the conquest of disease.

BIBLIOGRAPHY

I. Original Works. Mimeographed bibliographies were prepared by Earl B. McKinley and Ellen G. Acree, and also by the library of the Rockefeller Institute for Medical Research (now Rockefeller University), New York, Published versions accompany the sketch of Smith’s life in Medical Classics, I (1936–1937), 347–371, and the biographical memoir by Hans Zinsser (see below), which respectively cite 224 and 247 items. These are all incomplete and contain inaccuracies. The actual total, excluding unverifiable editorials and multiple publications of the same article, is almost 300 titles.

His more important monographs include Hog Cholera; Its History, Nature and Treatment (Washington, 1889) written with D. E. Salmon and F. L. Kilborne; Special Report on the Cause and Prevention of Swine Plague (Washington, 1891); Investigations Into theNature, Causation, and Prevention of Texas or Southern Cattle Fever (Washington, 1893), written with F. L. Kilborne, repr. in Medical Classics. 1 (1936–1937), 372–597; Studies in Vaccinal Immunity Towards Disease of the Bovine Placenta Due to Bacillus Abortus (Infectious Abortion) (New York, 1923), written with R. B. Little: and Parasitism and Disease (Princeton, N.J., 1934), the Vanuxem lectures.

Smith’s lasting interest in the bacteriology and immunology of tuberculosis is expressed in “The Diagnostic and Prognostic Value of the Bacillus Tuberculosis in the Sputum of Pulmonary Diseases,” in Albany Medical Annals, 5 (1884), 193–198; “Some Practical Suggestions for the Suppression and Prevention of Bovine Tuberculosis,” in Yearbook of the United States Department of Agriculture (1895), 317–330; “Two Varieties of the Tubercle Bacillus From Mammals,” in Transactions of the Association of American Physicians. 11 (1896), 75–93; “A Comparative Study of Bovine Tubercle Bacilli and of Human Bacilli From Sputum,” in Journal of Experimental Medicine, 3 (1898), 451–511, repr. in Medical Classics,1 (1936–1937), 599–669: “The Thermal Death-point of Tubercle Bacilli in Milk and Some Other Fluids,” in Journal of Experimental Medicine,4 (1899) 217–233; “The Relation Between Bovine and Human Tuberculosis.” in Medical News, 80 (1902), 343–346; “Studies in Mammalian Tubercle Bacilli. III . Description of a Bovine Bacillus From the Human Body. A Culture Test for Distinguishing the Human From the Bovine Type of Baccilli,” in Transactions of the Association of American Physicians, 18 (1903), 109– 151; “The Parasitism of the Tubercle Bacillus and Its Bearing on Infection and Immunity,” inJournal of the American Medical Association, 46 (1906), 1247–1254, 1345–1348, the Harvey lecture: “Certain Aspects of Natural and Acquired Resistance to Tuberculosis and Their Bearing on Preventive Measures,” ibid.,68 (1917), 669–674, 764–769, the Mellon lecture; and “Focal Cell Reactions in Tuberculosis and Allied Diseases,” in Bulletin of the Johns Hopkins Hospital, 53 (1933), 197–225, the Thayer lectures.

His main contributions to the bacteriology and immunology of diphtheria are “Antitoxic and Microbicide Powers of the Blood Serum After Immunization, With Special Reference to Diphtheria,” in Albany Medical Annals, 16 (1895). 175– 189: “The Production of Diphtheria Antitoxin,” in Journal of the Association of Engineering Societies, 16 (1896), 83–92; “the Conditions Which Influence the Appearance of Toxin in Cultures of the Diphtheria Bacillus,” in Transactions of the Association of American Physicians, 11 (1896), 37–61; “The Relation of Dextrose to the Production of Toxin in Bouillon Cultures of the Diphtheria Bacillus,” in Journal of Experimental Medicine, 4 (1899), 373–397; “The Antitoxin Unit in Diphtheria.” in Journal of the Boston Society of Medical Sciences, 5 (1900), 1–11; “The Degree and Duration of Passive Immunity to Diphtheria Toxin Transmitted by Immunized Female Guinea-pigs to Their Immediate Offspring,” in Journal of Medical Research. n.s. 11 (1907), 359–379; and “Active Immunity Produced by So-called Balanced or Neutral Mixtures of Diphtheria Toxin and Antitoxin,” in Journal of Experimental Medicine, 11 (1909), 241–256.

Other fundamental contributions to immunology are “On a New Method of Producing Immunity From Contagious Diseases.’” in Proceedings of the Biological Society of Washington, 3 (1886), 29–33. and “Experiments on the Production of Immunity by the Hypodermic Injection of Sterilized Cultures,” in Transactions of the IX International Medical Congress, Washington, 3 (1887), 403–407, both written with D. E. Salmon; “The Agglutination Affinities of Related Bacteria Parasitic in Different Hosts,” in Journal of Medical Research, n.s. 4 (1903), 270–300, and “The Non-identity of Agglutinins Acting Upon the Flagella and Upon the Body of Bacteria,” ibid., n.s. 5 (1903). 89– 100, both written with A. L. Reagh: “Agglutination Affinities of a Pathogenic Bacillus From Fowls (Fowl Typhoid) Bacterium sanguinarium, Moore) With the Typhoid Bacillus of Man,” ibid., n.s. 26 (1915), 503–521, written with C. Ten Broeck; “The Significance of Colostrum to the New-born Calf,” in Journal of Experimental Medicine, 36 (1922), 181–198, written with R. B. Little; and “The Relation of the Capsular Substance of B. coli to Antibody Production,” ibid., 48 (1928), 351–361.

His studies on the properties and differentation of new or unusual bacterial species include “A New Chromogenous Bacillus,” in Proceedings of the American Association for the Advancement of Science, 34 (1885), 303–309, written with D. E. Salmon: “The Bacterium of Swine Plague,” in American Monthly Microscopical Journal, 7 (1886), 204–205: “A Contribution to the Study of the Microbe of Rabbit Septicaemia,” in Journal of Comparative Medicine and Surgery, 8 (1887), 24–37; “Zur Unterscheidurtg z wise hen Typhus- und Kolonbicillen,” in Centralblatt für Bakterlohgie und Parasitenkunde (Original-Mittheilung), 11 (1892), 367–370; “On a Pathogenic Bacillus From the Vagina of a Mare After Abortion,” in Bulletin. Bureau of Animal Industry United States Department of Agriculture, no. 3 (Washington, 1893), 53–59; “Spontaneous Pseudo-tuberculosis in a Guinea-pig, and the Bacillus Causing It,” in Journal of the Boston Society of Medical Sciences, 1 (1897), 5–8; “Ueber die pathogens Wirkung des Bacillus abortus Bang,” in Centralblatt für Bakteriologie Parasitenkunde und Infektionskrankheiten,I . Abteilung (Originale), 61 (1912), 549–555; “A Pleomorphic Bacillus From Pneumonic Lungs of Calves Simulating Actinomyces,” in Journal of Experimental Medicine, 28 (1918), 333–344; “Spirilla Associated With Disease of the Fetal Membranes in Cattle (Infectious Abortion),” ibid., 701–719; “Some Cultural Characters of Bacillus abortus (Bang) With Special Reference to CO2 Requirements,” ibid., 40 (1924), 219–232; “Studies on a Paratyphoid Infection in Guinea Pigs,” ibid., 45 (1927), 353–363, 365–377, written with J. B. Nelson; and “Studies on Pathogenic B. coli From Bovine Sources,” ibid., 46 (1927), 123–131, written with R. B, Little.

Smith’s persistent concern with bacterial variation is apparent from “On the Variability of Pathogenic Organisms, as Illustrated by the Bacterium of Swine-plague,” in American Monthly Microscopical Journal, 7 (1886), 201–203; “Observations on the Variability of Disease Germs,” in New York Medical Journal, 52 (1890), 485–487; “Modification. Temporary and Permanent, of the Physiological Characters of Bacteria in Mixed Cultures,” in Transactions of the Association of American Physicians, 9 (1894), 85–106; “Variations Among Pathogenic Bacteria,” in Journal of the Boston Society of Medical Sciences, 4 (1900), 95–104; “Animal Reservoirs of Human Disease With Special Reference to Microbic Variability,” in Bulletin of the New York Academy of Medicine, 2nd ser., 4 (1928), 476–496; and “Koch’s Views on the Stability of Species Among Bacteria.” in Annals of Medical History, n.s. 4 (1932), 524–530.

His pioneering work on the bacteriological analysis of water is expressed in “Some Recent Investigations Concerning Bacteria in Drinking Water,”in Medical News, 49 (1886), 399–401; “Quantitative Variations in the Germ Life of PotomacWater During the Year 1886,” ibid., 50 (1887), 404–405: “The Relation of Drinking Water to Some Infectious Diseases,” in Albany Medical Annals, 9 (1888), 297–302; “On Pathogenic Bacteria in Drinking Water and the Means Employed for their Removal,” ibid., 13 (1892), 129– 150; “A New Method for Determining Quantitatively the Pollution of Water by Fecal Bacteria,” in New York State Board of Health. Thirteenth Annual Report for the Year 1892 (1893), 712–722; “Notes on Bacillus coli communis and Related Forms, Together With Some Suggestions Concerning the Bacteriological Examination of Drinking-water,” in American Journal of the Medical Sciences, 110 (1895), 283–302; and “Water-borne Diseases,” in Journal of the New England Water Works Association, 10 (1896), 203–225.

On other aspects of sanitation he wrote “Recent Advances in the Disinfection of Dwellings as Illustrated by the Berlin Rules,” in New York Medical Journal. 48 (1888), 117– 120; “The Sanitary Aspects of Dairying,” in Maine Farmer (15 Dec. 1898), 1, 4; “The House-fly as an Agent in the Dissemination of Infectious Diseases,” in American Journal of Public Hygiene, n.s. 4 (1908), 312–317; “What Is Diseased Meat and What Is Its Relation to Meat Inspection?,” ibid., n.s. 5 (1909), 397–411; and “Insects as Carriers of Disease,” in Monthly Bulletin of the State Board of Health of Massachusetts,5 (1910), 112– 119.

The scope and duration of Smith’s work in parasitology is exemplified by “Some Observations on Coccidia in the Renal Epithelium of the Mouse,” in Journal of Comparative Medicine and Surgery, 10 (1889), 211–217; “Preliminary Observations on the Microorganism of Texas Fever,” in Medical News, 55 (1889), 689–693; “Some Problems in the Etiology and Pathology of Texas Cattle Fever, and Their Bearing on the Comparative Study of Protozoan Diseases,” in Transactions of the Association of American Physicians, 8 (1893), 117–134; “An Infectious Disease Among Turkeys Caused by Protozoa (Infectious Entero-hepatitis),” in Bulletin, Bureau of Animal Industry. United States Department of Agriculture, no. 8 (1895), 7–38: “The Etiology of Texas Cattle Fever, With Special Reference to Recent Hypotheses Concerning the Transmission of Malaria,” in New York Medical Journal, 70 (1899), 47–51; “The Etiology of Malaria With Special Reference to the Mosquito as an Intermediate Host,” in Journal of the Massachusetts Association of Boards of Health, 11 (1901), 99–113; “The Production of Sarcosporidiosis in the Mouse by Feeding Infected Muscular Tissue,” in Journal of Experimental Medicine, 6 (1901), 1-21; “On a Coccidium (Klossiella muris, gen. et spec, nov.) Parasitic in the Renal Epithelium of the Mouse,” ibid., 6 (1902), 303–316, written with H. P. Johnson; “The Sources, Favoring Conditions and Prophylaxis of Malaria in Temperate Climates, With Special Reference to Massachusetts,” in Boston Medical and Surgical Journal, 149 (1903), 57–64, 87–92, 115–118, 139–144, the Shattuck lecture: “Some Field Experiments Bearing on the Transmission of Blackhead in Turkeys,” in Journal of Experimental Medicine, 25 (1917), 405–414; “Coccidiosis in Young Calves,” ibid., 28 (1918), 89–108; and “Encephalitozoon cuniculi as a Kidney Parasite in the Rabbit,” ibid., 41 (1925), 25–35.

Technological innovations and elucidations are reported in “A Few Simple Methods of Obtaining Pure Cultures of Bacteria for Microscopical Examination,” in American Monthly Microscopical Journal, 7 (1886), 124–125; “The Fermentation Tube With Special Reference to Anaërobiosis and Gas Production Among Bacteria,” in Wilder Quarter-Century Book 1868–1893 (Ithaca, 1893), 187–233; “Ueber die Bedeutung des Zuckers in Kulturmedien für Bakterien,” in Centralblatt für Bakteriologie und Parasitenkunde, I . Abteilung (Originale), 18 (1895), 1–9: “A Modification of the Method for Determining the Production of Indol by Bacteria,” in Journal of Experimental Medicine, 2 (1897), 543–547; and “One of the Conditions Under Which Discontinuous Sterilization May be Ineffective,” ibid., 3 (1898), 647–650,