ZINSSER, HANS

(b. New York, N. Y., 17 November 1878; d. New York, 4 September 1940)

bacteriology, immunology.

Zinsser was the youngest son of August Zinsser, a German immigrant who had founded a prosperous chemical products business. The household retained many Old World features, and German was Zinsser’s primary language until he was ten years old . He was also steeped in French literature and culture from his childhood . His early education at the fashionable private school run by Julius Sachs was supplemented by frequent trips to Europe as well as by a year of study at Wiesbaden, Germany.

In 1895, Zinsser entered Columbia College, where George Edward Woodberry, professor of comparative literature, cultivated his poetic imagination. His enthusiasm for science was the result of courses under Edmund B. Wilson and Bashford Dean. He never lost either enthusiasm, but science became his profession and poetry a seriously practiced avocation. Zinsser graduated from the College of Physicians and Surgeons of Columbia University in 1903, receiving both the M.D. and the M.A. He interned at Roosevelt Hospital from 1903 to 1905, and after three years of desultory medical practice accepted a full-time appointment at Columbia as instructor in bacteriology. From 1907 until 1910 he was also assistant pathologist at St. Luke’s Hospital. In 1910 Zinsser went to Stanford University, where in 1911 he was appointed professor of bacteriology and immunology. He was recalled to a similar position at Columbia in 1913. From 1923 until his death Zinsser taught at the Harvard Medical School, becoming Charles Wilder professor of bacteriology and immunology in 1925.

In 1905 Zinsser married Ruby Handforth Kunz; they had a son and a daughter. He received numerous honors and awards, including honorary doctorates from Columbia, Western Reserve, Lehigh, Yale, and Harvard. He was decorated with the French Legion of Honor and the American Distinguished Service Medal, and served as president of both the American Association of Immunologists (1919) and the Society of American Bacteriologists (1926).

Zinsser’s professional interests ranged from theoretical questions involving the physicochemical nature of the antigen-antibody reaction to practical problems of military santitation and the epidemiology of infectious diseases. He visited Serbia in 1915 as a member of the American Red Cross Sanitary Commission and studied at first at hand an outbreak of epidemic typhus. His field investigations of typhus later took him to the Soviet Union (1923), Mexico, (1913), and China (1938). Zinsser described these experiences in two engaging books, Rats, Lice and History (1935) and As I Remeber Him(1940). The former book, which he called a “biography mixture of history of typhus,” was a Rebelaisian mixture of history, wit, philosophy, and science that achieved instant popularity. As I Remember Him, although written in the third person, is autobiographical. Its subject-“R.S.”-is Zinsser himself, those letters forming the pseudonym under which he published poems in the Atlantic Monthly and other periodicals. In his autobiography Zinsser exhibited much of the playfulness and penchant for digression that characterized the earlier popular study of typhus. Writing the book while suffering from lymphocytic leukemia, he movingly recorded his subjective reactions to the disease that was causing his death.

Zinsser dedicated Rats, Lice and History to his friend Charles Nicolle, the French bacteriologist, novelist, and philosopher who received the 1928 Nobel Prize in medicine or physiology for his studies on the natural history of typhus. Nicolle and his colleagues had proved that epidemic typhus is louse-borne, and had infected monkeys and guinea pigs with the causative organism (Rickettsia prowazekii), thus providing convenient laboratory models for studying host response to the disease. The relationship of louse-borne epidemic typhus to the sporadic, endemic variety of the disease prevalent in the southeastern regions of the United States was poorly understood. Endemic typhus was generally grouped with another form of typhus first described in 1898 by N. E. Brill, who found it among immigrants in New York City. In the 1920’s and 1930’s Hermann Mooser and others proved that the etiologic agent of murine (endemic) thyphus is another species of Rickettsia (since named R.mooseri). The rat flea, rather than the louse, serves as the pricipal vector in tramsmitting this variety of thyphus. In the early 1930’s Zinsser and his associates suggested that Brill’s disease is clinically distant from murine typhus. Zinsser then demonstrated that the caustive organism in Brill’s disease is R. prowazekii rather than R. mooseri. He hypothesized that Brill’s disease reprfesented recrudescent typhus in patients who have already recovered from a primary attack of epidemic typhus. His hypothesis has since been confirmed epidemiologically and serologically, and Brill’s disease has been renamed Brill-Zinsser’s disease.

Zinsser and his associates, who included M. Ruiz Castaneda, Harry Plotz, S. H. Zia, and J. F. Enders, also worked on the production of an effective vaccine against typhus. From these studies came important new tissue culture methods for growing Rickettsia. Zinsser and his associates also developed improved staining techniques for Rickettsia in both smears and tissue cultures.

Zinsser’s name is thus intimately connected with the development of modern knowledge of rickettsial diseases, an association cemented by the popularity of Rats, Lice and History. Nevertheless, his typhus studies represent only a portion of his scientific output. Zinsser also did important work on the nature of the antigen-antibody reaction, the etiology of rheumatic fever, the phenomena of delayed hypersensitivity and allergy, the measurement of virus size, and the host response to syphilis.

His concern with the fundamental problems of immunology began about the time Zinsser went to Stanford (1910). He was convinced that physical chemistry would ultimately provide the means of understanding the reactions between antigens and antibodies. Accordingly, he attempted to rectify the deficiencies in his own mathematical and chemical competence. This conviction also led to his collaboration with Stewart Young, professor of colloid chemistry at Stanford, with whom he investigated colloidal aspects of the precipitin reaction. Zinsser’s first work on the influence of heat on antigens also dates from his time at Stanford. From the solutions of bacteria and their metabolic products used to immunize laboratory animals, he identified various heat-resistant fractions with pronounced antigenic properties. Since proteins are denatured by heat (and acid), he thus showed that other classes of compounds besides proteins can be antigenic. Zinsser’s studies of tuberculin hypersensitivity and allergy led him to stress the importance of nonprotein bacterial products in the immune response. He was the first to formulate clearly the distinction between the tuberculin type of allergic reaction and classic anaphylactic shock.

In addition to his work on immunologic aspects of tuberculosis, Zinsser studied various hyperimmune and allergic phenomena associated with streptococcal and pneurnococcal infections. He was one of several scientists in the 1910’s and 1920’s to suggest that diseases such as rheumatic fever and glomerulonephritis result from hypersensitivity to toxins produced by certain strains of Streptococci.

Between 1926 and 1930 Zinsser published a number of papers on the herpes virus and on herpes encephalitis. He and Fei-fang Tang undertook to measure virus sizes by passing viruses through graded filters. They obtained good approximations, although more sensitive techniques have since been developed.

Zinsser’s research interests thus covered a spectrum of bacteriological and immunological problems. He also produced two systematic treatises. A Textbook of Bacteriology was first published in 1910, in collaboration with Philip H. Hiss, Jr., a Columbia bacteriologist. This book passed through eight editions during Zinsser’s lifetime and was translated into several foreign languages, including Chinese. After Hiss’s death in 1913, Zinsser collaborated with Stanhope Bayne-Jones in the production of the seventh and eighth editions, and through Bayne-Jones and others, the Textbook reached the fourteenth edition (1968).

Infection and Resistance (1914) was Zinsser’s other major book. His own contributions to immunology may be traced through the successive editions of this work, last published in 1939 in collaboration with John Enders and Henry D. Fothergill as Immunity : Principles and Application in Medicine and Public Health.

Literature, history, politics, education, art, music, and philosophy also came within Zinsser’s ken. He played an active role in university life at Harvard in the 1920’s and 1930’s, and taught his pupils and research associates far more than the principles of bacteriology.

BIBLIOGRAPHY

I. Original Works. The various eds. of Zinsser’s Textbook of Bacteriology (New York-London, 1910), written with Philip H. Hiss, Jr., and Infection and Resistance (New York, 1914) give good accounts of his own work in relation to the developing disciplines of bacteriology and immunology. The following papers deal with particular aspects in greater detail : “On the Possible Importance of Colloidal Protection in Certain Phases of the Precipitin Reaction,” in Journal of Experimental Medicine, 17 (1913), 396-408,written with Stewart Young; “Studies on the Tuberculin Reaction and on Specific Hypersensitiveness in Bacterial Infection,” ibid., 34 (1921), 495-524; “On the Significance of Bacterial Allergy in Infectious Disease,” in Bulletin of the New York Academy of Medicine, 2nd ser., 4 (1928), 351-383; “Studies in Ultrafiltration,” in Journal of Experimental Medicine, 47 (1927), 357-378, written with Fei-fang Tang; “The Bacteriology of Rheumatic Fever and the Allergic Hypothesis,” in Archives of Internal Medicine42 (1928), 301-309, written with H. Yu; and “Varieties of Typhus Fever and the Epidemoilogy of the American Form of European Typhus Fever (Brill’s Disease),” in American Journal of Hygiene,20 (1934), 513-532.

Books by Zinsser not mentioned in the text are A Laboratory Course in Serum Study (New York, 1916), written with J. G. Hopkins and Reuben Ottenburg; and Spring. Summer and Autumn (New York, 1942), a volume of poems.

A full bibliography of Zinsser’s writings is appended to Simeon Burt Wolbach’s memoir in Biographical Memoirs. National Academy of Sciences, 24 (1947), 323-360.

II. Secondary Literature. In addition to the Wolbach memoir, other valuable obituaries include those of S. Bayne-Jones, in Archives of Pathology,31 (1941), 269-280; J. F. Enders, in Harvard Medical Alumni Bulletin,15 no. 1 (1940), supp., 1-15; J. H. Mueller, in Journal of Bacteriology,40 (1940), 747-753. Zinsser’s contributions to the study of typhus were summarized by P. K. Olitsky, “Hans Zinsser and His Studies on Typhus Fever,” in Journal of the American Medical Association, 116 (1941), 907-912.

William F. Bynum