(Issue 9 · posted May 30, 1997; archived June 13, 1997)
The years 1875 to 1910 are often called the golden era of microbiology. It was then that almost all of the bacteria causing human disease were identified, along with many human parasites, and when the science of virology was begun. No previous era in the history of medicine witnessed such a rapid succession of great discoveries.
Two books embody the spirit and sense of the golden age of microbiology. One, Microbe Hunters by Paul de Kruif, is nonfiction. The other is Sinclair Lewis's novel Arrowsmith. Biologists can read these books today not just for pleasure, but also for the enduring insights they still provide into the very human enterprise we call science. Research methodology may constantly change, but human nature doesn't. Lewis's and de Kruif's descriptions of scientific types are as trenchant and pertinent today as they were 70 years ago.
No doubt de Kruif was able to capture the excitement of the new science so
well because he had been educated as a bacteriologist. His father wanted him
to be a doctor, and the dutiful son began premedical studies at the University
of Michigan. But during his second year he was inspired to change his field by
an article about Paul Ehrlich, the German scientist who discovered a cure for
syphilis.
After receiving a bachelor of science degree in 1912, de Kruif obtained a Rockefeller fellowship to do bacteriologic research at the University of Michigan. In 1916 he received his Ph.D. With World War I raging in Europe, the young scientist joined the Army's Sanitary Corps in France. While in the service he discovered a quick, practical method of producing antitoxin for Clostridium welchii, the bacterium of gas gangrene.
After the war, de Kruif returned to Michigan to do research. Already married and a father, his inadequate university salary left him gasping for cash. Drawing upon his literary interests, de Kruif wrote to his idol, the irascible H.L. Mencken, asking advice. Mencken's suggestion, freelance writing, proved to be a mixed blessing.
While at Michigan, de Kruif wrote a noteworthy scientific article describing his studies of the blood-dissolving poison of the hemolytic streptococcus. This paper led to his appointment in 1920 as associate at the Rockefeller Institute for Medical Research (now Rockefeller University) in New York. Here he might have spent his life as a researcher but for his pronounced mischievous streak. He wrote a rakish book, Our Medicine Men, published in 1922, which he described as "a spoof of the exaggerated pretensions of a part of the medical profession." But that part consisted of colleagues at the Rockefeller Institute, parodied in thinly disguised caricatures.
"It caused me to get fired," de Kruif said some years later. "Exiled from science, I grubbed for a living, writing about medical science for popular magazines." He was in Chicago in 1922, busily grubbing, when a friend, Dr. Morris Fishbein, introduced him to Sinclair Lewis.
At this time, the 37-year-old Lewis was at a career zenith, buoyed by the
enormous successes of Main Street and Babbitt. He was
considering a Christlike labor leader as the hero of a third book, and was in
Chicago to talk to Eugene Debs, on whom he intended to pattern his
protagonist. But, after a long and boisterous evening of drinking in roadhouse
after roadhouse, de Kruif and Fishbein changed the author's mind. By early
morning, Lewis had decided to write a novel about medical science.
Lewis himself was quite familiar with the medical profession. Several members of his family were, or had been, members. And, as a student at Yale, Lewis had considered it for himself.
Lewis quickly struck a bargain with de Kruif and the publisher Alfred Harcourt to produce a novel about the medical profession. De Kruif, who would provide the background information, was to receive 25% of the royalties, a $10,000 advance, and an acknowledgment in the book. Lewis was to receive the rest. Together the two men began work, after a last night of carousing, on a freighter cruise to the West Indies.
The purpose of the cruise was twofold. First, since the novel's climax was to be a plague on a tropical island, travel was essential to assimilate the atmosphere of Caribbean life. But second and more important, the time at sea was needed to educate Lewis in bacteriology, epidemiology, and the method as well as the spirit of research.
By the end of the cruise much of the plot had already been shaped. De Kruif had written complete professional histories of the main characters, Martin Arrowsmith and Max Gottlieb. He had also helped to shape other characters who would appear in the developing plot. As Lewis wrote, de Kruif continued to provide assistance for additional technical information.
De Kruif's contributions to the story first appear when young Martin Arrowsmith begins his medical studies at the University of Winnemac. The technical experience of life in a medical school no doubt came partly from Lewis's brother Claude as well as from de Kruif. The character of Max Gottlieb - the most important figure in the book next to Arrowsmith - derives principally from Jacques Loeb, for whom de Kruif had worked as research associate at the Rockefeller Institute.
Loeb, a German biologist, was famous for his experiments on parthenogenesis (reproduction without fertilization). Popular interest and some controversy had attended the announcement of this work in 1899, for Loeb had successfully induced the development of sea urchin larvae from unfertilized eggs merely by exposing them to controlled environmental changes. Loeb later extended the technique to produce parthenogenetic frogs, which he raised to sexual maturity. He thereby demonstrated that the initiation of cell division in fertilization was controlled chemically and was separated from the transmission of hereditary traits. His studies of cellular chemistry led Loeb to espouse the belief that life phenomena can be explained by physical and chemical laws (see sidebar 1).
De Kruif and Lewis produced their most wicked caricature in the person of the McGurk (Rockefeller) Institute's director, Dr. A. DeWitt Tubbs. Clearly, de Kruif was bitter over his discharge from Rockefeller for what seemed nothing more than a harmless joke. He took revenge by mercilessly patterning Tubbs on Rockefeller's own director, Dr. Simon Flexner.
Flexner was an internationally famous pathologist and bacteriologist. A gifted researcher, he had isolated the dysentery bacillus, Shigella flexneri, and developed a curative serum for cerebrospinal meningitis. During his directorial tenure at Rockefeller, when de Kruif came to know him, Flexner was leading a research team studying poliomyelitis (see sidebar 2).
There had been other novels written about doctors, even about those who vacillated between lucrative private practice and professional integrity. Arrowsmith, however, is not primarily about a doctor but a research scientist fighting for his scientific integrity. Martin Arrowsmith was a new kind of hero, and scientific idealism a new subject. Few subsequent novels have portrayed so well the agonies and joys of a medical researcher working in the new world that evolved from the golden age of microbiology.
After Arrowsmith, Sinclair Lewis wrote two other famous books, Elmer Gantry and Dodsworth. In 1930 he received the Nobel Prize for literature. But the heavy drinking and the changing times were taking their toll. Lewis published ten more novels, but none measured up to his previous work. After World War II he continued to travel widely, and in September 1949 sailed for Italy. There he took his last drink - one too many - and died in delirium tremens at the age of 65.
De Kruif may well have taken perverse pleasure from Lewis's tragic demise because of the bad feeling that had erupted between the two men after Arrowsmith was completed. He expected to receive the acknowledgment "In collaboration with Paul de Kruif" on the title page. Instead, Lewis offered a generous but more qualified blurb on the following page, which de Kruif was ultimately forced to accept. In later editions of the book, Lewis's acknowledgment to de Kruif was replaced by a lengthy editorial introduction detailing precisely the contributions of both authors. Nonetheless, de Kruif refused to collaborate with Lewis again.
And he really didn't need to. During the writing of Arrowsmith, de Kruif had collected material about the scientists responsible for the germ theory. Deciding that he lacked Sinclair Lewis's aptitude for writing fiction, he produced the now-famous book Microbe Hunters, published in 1926.
Microbe Hunters is a lively, factual account of the men who brought about microbiology's golden age. By 1971 it had sold more than a million copies and had been widely translated. Famous scientists have remarked that they were inspired to enter medical research after reading it. Even a few critics approved of it.
Yet the last word about the golden age belongs to Sinclair Lewis. Microbe Hunters did not ponder the future. Arrowsmith did. Before Martin Arrowsmith is sent to fight the plague epidemic on St. Hubert, he makes a remarkable discovery. In the pus from a carbuncle he identifies a substance capable of killing the bacteria in an infected wound without harming the host tissue. Night and day he works to isolate and purify this substance until he is pushed to near-psychosis by the strain. For Martin believes that he has found the long-sought drug that can cure any bacterial infection in man. Such a drug was, indeed, being assiduously looked for by many scientists.
In fact, what Martin Arrowsmith isolates is a bacteria-infecting virus called a phage. Because he delays publishing until all details have been clarified, he loses priority to a French researcher, Felix d'Herelle of the Pasteur Institute. And, in the end, the phage turns out to be worthless as a therapeutic agent.
In 1928, four years after Arrowsmith was published, Alexander Fleming, a British bacteriologist, accidentally discovered a real substance capable of killing bacteria without harming the host - penicillin. The story of how this long hoped-for new drug finally came into use was more surprising and ironic than even Martin Arrowsmith could have imagined.
But the scientific traits Martin Arrowsmith encounters are unchanged today. The petty jealousies, vengefulness, pompous pride, fear of being scooped on a discovery, job insecurity: All are familiar to modern scientists. Yet, as in Arrowsmith, the enormous personal satisfaction that can come from doing science is ever present, a gratification unique to scientific endeavor.
Steven P. Lehrer, M.D., is Associate Professor of Radiation Oncology at Mount Sinai School of Medicine in New York.
Endlinks
Arrowsmith - Sinclair Lewis's book has been recently reissued.
Microbe Hunters - this edition of Paul de Kruif's book contains a new introduction by F. Gonzalez-Crussi.
Microbe Hunters: Then and Now - readers may enjoy this new book edited by Hilary Koprowski and Michael B.A. Oldstone; it describes the efforts behind recent discoveries in infectious diseases.
The Search for Solutions - Horace Freeland Judson's 1987 book of excellent narratives about research scientists.
Beyond the Laboratory: Scientists as Political Activists in 1930s America - Peter J. Kuznick's 1987 book.
New York University School of Medicine - Readers interested in medical humanities should explore this Web site. This site is the worldwide hub for resources on the topic. Included here are a database for literature, arts, a medicine database (also available in hardcopy), the Archives of the Literature and Medicine mailing list, a directory of people and programs, syllabi, and student essays. The site links to several other medical humanities and bioethics sites.
"Rethinking Microbe Hunters" - this article, published in the American Society for Microbiology newsletter, indicts the racial, cultural, and gender-specific elitism presented in Paul de Kruif's book.
Images from the History of the Public Health Service: A Photographic Exhibit - an online exhibit by Ramunas Kondratas, Ph.D., from the U.S. National Library of Medicine.
Outstanding Papers in Biology - HMS Beagle contributor Walter Gratzer's reflection on the classic studies in science.
Finally, we may be entering an important new era in the study of microbes, as suggested by the May 2, 1997 issue of Science magazine, which was devoted to frontiers in microbiology.