Immunology and Culture

Paul de Kruif and Microbe Hunters

by John S. Emrich and Charles Richter
January/February 2019, pages 20–23

If one book, more than any other, drew scientists toward the field of immunology in the first half of the 20th century, it is most likely Microbe Hunters by Paul de Kruif (rhymes with “life”). The sweeping work of history—spanning Anton van Leeuwenhoek’s discovery of microbes in the 17th century through Paul Ehrlich’s “magic bullet” targeting syphilis in 1909—has remained in print since its original publication in 1926 and inspired not only generations of immunologists but also many adaptations as well.

Legitimate scientific credentials were behind the fame de Kruif (AAI 1921) achieved as a writer of popular science. Having obtained his Ph.D. (1916) from the University of Michigan under the mentorship of Frederick Novy (AAI 1920, president 1924–25), de Kruif enlisted in the U.S. Army and participated in the Mexican Expedition against Pancho Villa in 1916–17. Later, as a member of the Army’s Sanitary Corps during World War I, he created a method for more rapid production of an antitoxin to Clostridium perfringens, a major cause of gas gangrene during the war.

Following the war and his return to the University of Michigan as an assistant professor, de Kruif fell in love with a laboratory assistant, Elizabeth (“Rhea”) Barbarin. Already married with two small children, de Kruif divorced his first wife and soon married Barbarin, which created a financial strain. To meet his new obligations, de Kruif, at the encouragement of his literary idol, H. L. Menken, undertook freelance writing while continuing his teaching and laboratory research with Novy. The latter endeavor soon proved fruitful, as his research on hemolytic streptococcus and anaphylatoxins caught the eye of scientists, including Simon Flexner (AAI 1920), at the Rockefeller Institute for Medical Research (RIMR; now the Rockefeller University).

As a result of his growing prominence, de Kruif was appointed as an associate at RIMR and began work in the laboratory of Flexner. By then, however, de Kruif was already becoming disillusioned by the state of medical research and practice. He believed that increasing specialization was robbing the field of thoughtful generalists thus detaching it from the immediate needs of patients and allowing moral crusades to exert too much control over the direction of research.

de Kruif’s first forays into writing about science, although published anonymously, nevertheless got him “fired” from Flexner’s lab. In a series of four articles in The Century Magazine and a chapter in Harold E. Stearns’s Civilization in the United States, de Kruif framed the medical field as becoming increasingly driven by profit, novelty, and moral crusading. He condemned this trend as “medical Ga-Gaism.” When Flexner discovered the true authorship of the publications, he saw them as an attack on RIMR and asked for de Kruif’s resignation in 1922. de Kruif complied but nonetheless published a collected and expanded edition of the offending essays dedicated to “my teacher of bacteriology…without his permission.”

de Kruif’s dismissal from RIMR left him free to collaborate with celebrated author Sinclair Lewis on the Pulitzer-winning novel Arrowsmith, the story of a scientist torn between the rigors of pure science and the demands of public health crises. To prepare for the novel, he and Lewis boarded a tramp steamer bound for the Caribbean. In the islands, they indulged in the sampling of tropical cocktails while producing a 60,000- word outline for the novel, drawing on their experiences in the region and de Kruif’s scientific knowledge. Lewis was impressed, not only by de Kruif’s technical contributions but also by his literary sensibilities. He later told H. G. Wells that de Kruif was “a man with a knife-edge mind and an iconoclasm that really means something.” The collaboration helped de Kruif as well: it taught him to write for a broader audience.

Arrowsmith was released in 1925 to wide critical acclaim. The book focuses on an issue that de Kruif had been weighing and writing about during the early part of the decade: the tension and conflict between medicine and basic research. The book’s protagonist, Martin Arrowsmith, is a microbe hunter who, after finding success in the Midwest, is invited to join a highly respected biomedical research institute in New York—echoing the narrative of de Kruif’s own life. It is in his capacity leading a biomedical research team that Arrowsmith faces the life-changing dilemma of having to choose between being faithful to basic science and his principles or betraying them.

It was during his work with Lewis on Arrowsmith that de Kruif’s next idea for a book emerged, with the sprouting of a seed planted years before by Jules Bordet (AAI '60), a colleague at RIMR. The work was to be a collection of stories profiling scientists and how their discoveries fundamentally altered the understanding of microbiology. de Kruif would start at the beginning with the microscope and carry his narrative to near present day, covering this history by telling 12 stories of 14 scientists. To many in the public and the scientific community, Microbe Hunters was the nonfiction sequel to Arrowsmith.

In 1926, when Microbe Hunters was released, the field of immunology was still young and, at times, produced hypotheses and discoveries that were at odds with prevailing theories in some of the older, more established biomedical fields. In his presidential address that year, Wilfred H. Manwaring (AAI 1917, president 1925–26) acknowledged the “skepticism with which many of the theoretical phases of our subject have been received by works in the older medical sciences.” He attributed this skepticism, in large part, to disagreement over Ehrlich’s receptor theory, which was being widely tested by new methods. Immunologists were also focused on the matter of blood typing, a topic of frequent discussion at the AAI annual meeting and in the pages of The Journal of Immunology.

Microbe Hunters opens with a quartet of pioneers who established the existence of microscopic organisms and demonstrated their role in disease. The first of these is van Leeuwenhoek, who first saw miniscule animals through his revolutionary microscope in the 17th century. de Kruif’s focus then turns to Lazzaro Spallanzani and the lengthy series of experiments he performed in an attempt to disprove spontaneous generation. Rounding out this section are Robert Koch’s identification of specific pathogens and their connection to diseases, and Louis Pasteur’s innovations in vaccines and the neutralization of microbes.

The book next focuses on the discoverers of mechanisms crucial to the immune system and understanding disease transmissions, as well as early developers of treatments and cures. By this time in the early 20th century, the hygiene theory was widely accepted, and the germ theory had been well established, thus making the modern biomedical setting more recognizable to the reader.

Elie Metchnikoff’s discovery of macrophages (“the nice phagocytes”) was a critical step in the understanding of innate immunity. Emile Roux and Emil von Behring developed the first successful diphtheria antitoxin, introducing serum therapy to the world. Theobald Smith (AAI 1920) proved that cattle were catching Texas fever from ticks, demonstrating that insects and other arthropods could act as disease vectors. Smith’s precedent led the way for the work of David Bruce (tsetse fly and sleeping sickness), Ronald Ross and Battista Grassi (mosquitoes and malaria), and Walter Reed (mosquitoes and yellow fever) .

The final microbe hunter featured in the book is Ehrlich, whose “magic bullet” against syphilis was the first example of successful chemotherapy treatment for a specific disease. de Kruif saw Ehrlich’s achievement as the practical culmination of the centuries of research performed by the other scientists profiled in the book.

In most of his early science writing, de Kruif adopted a sensationalist tone—and in Microbe Hunters, he was practically breathless. In keeping with the heroic age of medicine, he made his subjects larger-than-life heroes, frequently imagining dialogue that they would exclaim at moments of discovery. A book review in JAMA noted that de Kruif described the innovators as “far from the perfect and rather priggish members of the human race that they are sometimes represented to be” but that his style had “an exaggerated quality which is annoying.” The reviewer predicted that the book would be appreciated by scientists and a general audience alike.

Microbe Hunters found immediate and enormous success. It quickly became a national and international bestseller and was soon translated into 18 languages. Some subjects of the book, however, were less impressed. The most notable of these was Ross, the British scientist who received the 1902 Nobel Prize in Physiology or Medicine for identifying the role of the mosquito in malaria transmission.

Ross strenuously objected to how de Kruif portrayed his rivalry with Grassi. In an open letter, Ross, along with Aldo Castellani, George C. Low, David Nabarro, and Cuthbert Cristy, complained that de Kruif’s account was “almost entirely apocryphal…not supported by reference to the original literature…[and] clearly derived almost only from his own imagination or from spurious prompting by others.” Ross argued that some of de Kruif’s statements went so far as to violate British libel laws—and indeed, the British edition of Microbe Hunters was published without the chapters on Bruce and Ross. Notwithstanding the controversy, the book was a bestseller and has remained a staple of medical history.

The impact of Microbe Hunters went far beyond the printed page. In the 1930s and ’40s, adaptations of the book made their way to stage, radio, and screen, usually with de Kruif’s involvement. The author collaborated with another Pulitzer winner, Sidney Howard, to transform his chapter on Walter Reed into the play Yellow Jack in 1934.

The story of Reed battling yellow fever in Cuba at the end of the Spanish–American War gave a young Jimmy Stewart his first dramatic stage role as a young private who volunteers to be bitten by a mosquito in hopes of proving the method of transmission. Critics praised Yellow Jack, but this early translation from book to stage was not a hit at the box office. Nevertheless, four years later, the play was successfully adapted for the screen; the film’s cast featured Lewis Stone, who had actually served in the Spanish–American War, as Reed.

Under the Works Progress Administration of the New Deal, the Federal Theatre Project (FTP) produced hundreds of classic and original plays, including one adapted from de Kruif’s chapter on Ehrlich, with the unlikely title Spirochete. The play premiered in Chicago in 1938, just two years after U.S. Surgeon General Thomas Parran famously declared war on syphilis. Spirochete was a huge success, especially considering that the word “syphilis” had been considered almost too obscene for print just one year before. Theatergoers could even take a Wasserman test in the lobby during intermission. The show’s Seattle run was the most successful FTP production in the city, with 3,000 people attending the performances.

Americans did not have to go to the theater to hear stories of Microbe Hunters; they could also tune in to a weekly radio series. The FTP worked with de Kruif to adapt Microbe Hunters as the first 14 episodes of the radio drama series Men Against Death. The series ran weekly from June 30, 1938, to April 22, 1939, on the CBS network, dramatizing four of de Kruif’s books of popular science for a national radio audience.

The best known adaptation of Microbe Hunters is the 1940 film Dr. Ehrlich’s Magic Bullet, another production that pushed the boundaries of what was considered decent for the screen. Its topic was technically prohibited by the Motion Picture Production Code of 1934, which stated that “sex hygiene and venereal diseases are not acceptable subject matter for theatrical motion pictures.” Nevertheless, the search for a chemotherapeutic cure for syphilis was dramatized in a high-profile movie starring Edward G. Robinson as Ehrlich, with an Oscar-nominated script by John Huston.

The bulk of the film was shot in black and white, but the views of microscope slides were in Technicolor. In lieu of actual microphotography, however, the filmmakers used rubber models of syphilis spirochetes on giant slides and injected dye into them while activating them from below with wires. Critics praised the film for both its bold approach to a difficult topic and the performances of the cast.

For decades after its publication, Microbe Hunters was an inspiration and springboard for future biomedical researchers and doctors, and the book launched a new genre of science writing that flourishes to this day. Outdated as it is by current measure, both in terms of historical rigor and antiquated racial overtones, Microbe Hunters remains a classic documentary of the earliest microbiologists and immunologists and serves as an inspiration to new scientists. Today, de Kruif’s fast-paced narrative continues to be relevant to a wide audience as an exciting entry point into the origins of immunology and the field-shifting discoveries of its early years.



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