When the new novel Arrowsmith reached the nation’s bookstores in 1925, the author, Sinclair Lewis, was already the most celebrated American writer of the day.

His 1920 novel Main Street, a poignant satire of small-town America, had marked him as a major talent.

Then came Babbitt (1922), a meticulous dissection of middle-class conformity that had made Lewis famous.

Now the early reviews of Arrowsmith promised more renown. It was the first major American novel to feature a scientist in the leading role. That was an unlikely focus for a bestseller. But it was also a page-turner, a romance, a satire and a philosophical meditation on the tension between truth and good works.

It leaped to the first rank on bestseller lists. Critics declared that Lewis, once a scribbler of racy tales for mass-market magazines, had reached full maturity as an artist.

What neither Lewis nor his publishers said – at least not very loudly – was how much Arrowsmith owed to an obscure young scientist and what he had told Lewis about life in the medical labs of the University of Michigan.

Their friendship was short, stormy and profitable.

From Paul De Kruif (rhymes with life), Sinclair Lewis got facts and insights for a novel good enough to win the Pulitzer Prize (though Lewis turned it down) and to inspire generations of doctors and scientists.

From Lewis, De Kruif learned how to tell a story. He missed out on the credit he deserved for Arrowsmith. But by virtue of his accidental apprenticeship to Lewis, he was set up for his own pioneering career as a writer.

Born in 1890, Paul De Kruif had grown up in the Dutch-American village of Zeeland near Holland, Michigan. His father, a seller of farm equipment, hoped his son would become a doctor or lawyer. His mother read Mark Twain and George Eliot and encouraged her son to read widely, study hard and ask questions.

He entered U-M in 1908 as a pre-med student. When he read about the German physician-scientist Paul Ehrlich, who had explored the hidden world of microbes to discover a cure for syphilis, De Kruif changed his major. By 1916 he had a Ph.D. from U-M in microbiology.

Striding through the old Medical Building on East University, he made a powerful impression. He looked more like a Viking out of costume than a lab rat. He was tall, jug-eared and ruggedly handsome, with a thick outdoorsman’s trunk and an air of brawny energy. He had a bent for hero worship, and at Michigan he found a hero who would shape his life.

This was Frederick Novy, a new sort of figure in America’s medical schools. Novy was a pure scientist, not a physician. He had studied with Louis Pasteur and Robert Koch, the founders of microbiology. He was among the first American medical professors to probe the secrets of living beings whether they would lead to medical cures or not.

According to his biographer, Dr. Powel H. Kazanjian (professor of both internal medicine and history at U-M), Novy’s students learned “a comprehensive code that included a duty to search for truths in nature above all competing motives and the adoption of disciplined, methodical work habits.”

Paul De Kruif was one of many who came to see Novy as a secular saint, a model of scientific integrity and zeal. The two worked closely as mentor and disciple.

De Kruif gloried in the routines of the lab. Neglecting his first wife, he worked day and night, stopping only for an occasional plunge in the Huron, then racing back to his test tubes.

“That grubby den of research reeked of guinea pigs, white rats, and rabbits,” he later wrote. “In the primitive days of one’s work with Novy one raced three flights down to the basement and back up with wire baskets teeming with guinea pigs and battery jars alive with white rats…

“At Ann Arbor one burned one’s hands, blowing one’s own glassware for complex apparatus, and one washed one’s own test tubes and cooked the culture medium to feed one’s microbes. At Ann Arbor science was do-it-yourself.”

World War I interrupted. De Kruif spent two years in the U.S. Sanitary Corps trying to develop an antidote to poison-gas attacks.

Then he returned to Ann Arbor. Soon his work with Novy attracted the offer of a position at the prestigious Rockefeller Institute for Medical Research (now Rockefeller University) in New York. He accepted.

At Rockefeller he met the renowned German-American biologist Jacques Loeb, another pure scientist, who lampooned physicians as mere mechanics of the human body.  (“‘Medical science’?” Loeb remarked one day. “That is a contradiction in terms. There is no such thing.”)

De Kruif was close to making his own major name in research. But he conceived a strange new ambition, for a scientist. He wanted to explain science to a broad popular audience as a journalist.

Again he aimed high, writing for advice to the iconoclastic editor and critic H.L. Mencken, who saw literary promise in the young scientist’s letter. Mencken recruited him to write an article that would cast America’s mainstream “medicine men” in a deeply unflattering light. It was published anonymously, but word of De Kruif’s authorship got out. His Rockefeller bosses fired him.

Jobless and nearly broke, he put all his chips on a writing career and set off on a new topic — the unholy connections between M.D.s and drug manufacturers.

Then came his luckiest day.

In Chicago for research, De Kruif met Dr. Morris Fishbein, soon to be editor of the Journal of the American Medical Association, who happened to be in the company of – as De Kruif put it later – “a young red-headed man, very tall and slightly stooped, nervous, his face spotty red as if about the explode into a dermatosis … wild, freewheeling, intense, outlandish.”

This “unearthly character,” De Kruif learned, was none other than Sinclair Lewis, author of the mega-bestseller Main Street, apparently half-toasted though the sun had not yet set. He, too, was considering a book on the underside of American medicine.

After an uproarious night on the town, Lewis and De Kruif retired to Lewis’s hotel, where the novelist turned deadly serious, “every inch a writing pro,” asking “a hundred canny questions.

“He cross-examined me about why I’d left medicine for research on viruses, spirochetes, trypanosomes, and anaphylaxis under austere Frederick Novy,” De Kruif reported. “His questioning stirred me to make Professor Novy come alive, a figure of medical romance – our lab window the only one lighted far into the night in the medical building at Ann Arbor.”

Finally Lewis asked: How about if the two of them collaborated on a satirical novel about medicine and science? The hero could be a man like De Kruif himself, an idealistic, stubborn young scientist intoxicated by the search for truth. There could be a major character like Novy, a medical school like Michigan’s and a cast of minor characters drawn from De Kruif’s life.

De Kruif, flabbergasted, said that sounded fine.

* * *

Lewis brought DeKruif to New York to meet his publishers, Alfred Harcourt and Donald Brace. Though “not a word of it had yet got down on paper,” De Kruif recalled, Lewis talked through the outline of a long novel, a modern-day fable, “a saga…informed with the spirit of medical discovery, with a handsome, stubborn-minded young medical scientist the embattled hero.”

The publishers liked it. No one had done a big novel about medicine before.

Now Lewis made his pitch for DeKruif as co-author. The kid knew all the scientific dope the novel would need, he told the publishers, and he had great instincts for telling a story. Hell, it was going to be his story – the wide-eyed country boy pursuing scientific truth in a profession of medical Babbitts. So the cover should say “By Sinclair Lewis and Paul De Kruif” and the earnings should be split 50-50.

That wasn’t fair, De Kruif put in. Lewis had the big name and the talent. De Kruif should only get 25 percent of the earnings

The publishers agreed to the terms  – a 75/25 split of the money and equal credit on the cover  – for the moment.

De Kruif recalled that Alfred Harcourt, “out of his shrewd, sharp eyes, gave me a long look. It was not unkindly.”

Lewis had evolved a method for developing a novel. First he would sketch the book’s basic shape in his mind. Then he would research factual details, often taking a trip to do so. Next he would write a highly detailed outline, sometimes half as long as the novel itself. Then he would draft the novel in a sprint. Finally he would drop his pace to a crawl for a painstaking revision.

Lewis had imagined his hero fighting an epidemic in the tropics. So for his research trip, he decided on a cruise of the Caribbean aboard a rusty cargo steamer with De Kruif along to help him do his planning.

Lewis was itching to get going, but De Kruif said he couldn’t yet. He was scheduled to marry Rhea Barbarin, a former student of his at U-M, a native of Freeland, Michigan, a small town near Saginaw. They had put off the wedding for many months as De Kruif waited for his divorce to be final, and they had a honeymoon planned.

But Lewis said he couldn’t wait so long. He pressured De Kruif to cut his plans short; after the wedding he could bring Rhea east for a quick holiday before the working cruise to the Caribbean.

So De Kruif persuaded Rhea that the famous author, whose Midas touch might bring De Kruif his own chance at writing success, must be accommodated.

In New York, disillusionment awaited both De Kruifs.

Right away, Lewis took Paul aside to say Alfred Harcourt had deep-sixed the plan to list them as equal co-authors.

“Alf dopes it out this way,” Lewis said. “If the critics and the book buyers see Lewis and De Kruif on the cover, they’ll say Lewis is finished. He’s hiring an unknown to help write his book for him.”

“This sounded,” De Kruif wrote later, “like what’s on the floors of stables.”

What about the plan to split the money 75-25? he asked. That still stood, Lewis replied. So De Kruif swallowed his pride.

Late that night, drunk as usual, Lewis edged close to Rhea De Kruif. His own wife had gone off to bed. As De Kruif looked on, he wrote later, Lewis “began at first surreptitiously and then openly to try what could only be called necking” with Rhea. She froze and the writer backed off. De Kruif chose to overlook it.

Thereafter, as if nothing had happened, Lewis treated Rhea with respectful friendliness  – and used her as the model for Leora Arrowsmith, the admirable and long-suffering wife of his new protagonist.

Besides the crew, Lewis and De Kruif were the only ones aboard S.S. Guiana. The first morning out, Lewis took out his Corona typewriter. He and De Kruif talked and talked, and the outline began to emerge.

It was as if Lewis were a mining engineer, extracting raw materials from De Kruif’s mind and memory.

While Lewis worked on the master blueprint, De Kruif wrote a biographical synopsis of the fictional Martin Arrowsmith. It was a fictional facsimile of much of De Kruif’s own life.

In De Kruif’s synopsis, Arrowsmith is a boy in a small farm town like De Kruif’s Zeeland. He goes to a big state university like U-M (“the University of Winnemac”) where he becomes enthralled by a great scientist like Novy (“Max Gottlieb.”) He studies with medical professors and students modeled on ones De Kruif knew in Ann Arbor.

Like De Kruif, Arrowsmith shifts to pure science after becoming disillusioned with “the hypocrisy, charlatanism [and] loud advertisement” of mainstream medicine. He marries a down-to-earth nurse like Rhea (“Leora”) from a small town like Freeland (“Wheatsylvania.”) He works as a public health director in a center like one in Flint that De Kruif knew about. He accepts a position at a private research center in New York like the Rockefeller Institute (“McGurk Institute”), where scientists are pressured for quick results to keep up the institute’s prestige.

The two men filled a thick notebook. There were maps and diagrams of the novel’s locales; a biography of Arrowsmith’s fictional mentor, in whom De Kruif combined characteristics of Professor Novy and Jacques Loeb of the Rockefeller Institute; De Kruif’s descriptions of procedures in bacteriological research, down to drawings of lab equipment and microbes.

But it wasn’t just De Kruif giving to Lewis. The novelist was also imparting what he knew about storytelling to De Kruif, explaining how to draw the elements of drama from real life.

“Once facts had pinned him down, Red never tried to make do with phony movie science,” De Kruif would write. “He kept teaching me to let myself go to dramatize real science. …What a blissful experience this was for me, to try to learn to write all out, wildly, yet sticking to facts.”

“Beware of cliches,” Lewis said again and again. “Cliches are anathema.”

Lewis was fascinated by tensions in the material of De Kruif’s life.

There was the general practitioner’s compassion for his patient versus his sketchy grasp of human biology; the disinterested pursuit of truth for its own sake, represented by Novy, versus the pursuit of marketable cures, represented by the Rockefeller Institute. There was the public health movement’s noble effort to prevent disease versus superficial blather about cleanliness. There was the scientist’s zeal for untainted experiments, sacrificing untreated “controls” for the sake of finding the truth, versus the physician’s duty to heal all who suffered.

All these themes found places in Lewis’s notebook.

At the typewriter, Lewis permitted himself no liquor. When he left it  – for lunch, dinner, and all evening long  – a drink or four was always at hand. Yet ideas for the novel sprang to his mind even during his binges.

In Port of Spain, Trinidad, Lewis and De Kruif wandered into a notorious bar, the Ice House, where planter’s punches led the two into “a strange world of our imaginations,” as De Kruif put it. “They made us see a tropic island where death stank — the black death of the bubonic plague.”

In this grungy Caribbean saloon, Lewis spun a scenario for Martin Arrowsmith’s climactic choice between good science and good medicine.

The writer imagined it this way: 1) Arrowsmith has developed a promising serum for the plague; 2) to test it properly, he must dose half a population of patients with the actual cure and give the other half a placebo; 3) so he must choose: Should he honor the spirit of Gottlieb/Novy, saving thousands but dooming other thousands to a horrible death  – and thus prove the efficacy of his drug once and for all? Or should he give the cure to all the islanders, and thus sacrifice his devotion to truth? (Sorry — no spoilers here.)

Minor characters in the notebooks were modeled on figures from De Kruif’s past or people the travelers encountered along their journey.

From the medical faculty at U-M came good-hearted healers like “Dad” Silva, dean of the Winnemac medical school (a stand-in for Michigan’s Victor Vaughan?) but also Professor Roscoe Geake, an ear-nose-throat man who urged his medical students to chase every available dollar.

From some combination of De Kruif’s tales and Lewis’s own glancing knowledge of Midwestern universities (he had gone to Yale), the writer would develop a word-portrait of the “University of Winnemac,” circa 1910 that any reader of Babbitt might expect — keen-eyed and caustic in its view of mainstream American institutions:

…its buildings are measured by the mile; it hires hundreds of young Doctors of Philosophy to give rapid instruction in Sanskrit, navigation, accountancy, spectacle-fitting, sanitary engineering, Provencal poetry, tariff schedules … motor-car designing … and department-store advertising …

It is not a snobbish rich-man’s college, devoted to leisurely nonsense. It is the property of the people of the state, and what they want … is a mill to turn out men and women who will lead moral lives, play bridge, drive good cars, be enterprising in business, and occasionally mention books, though they are not expected to have time to read them. It is a Ford Motor Factory, and if its products rattle a little, they are beautifully standardized, with perfectly interchangeable parts.

De Kruif was dazzled by Lewis’s creative power. But the novelist was equally impressed by his apprentice.

“It gives me joy to inform you that de Kruif is perfection,” Lewis wrote his publishers soon after leaving New York. “He has not only an astonishing grasp of scientific detail, he has a philosophy behind it, and the imagination of a fiction writer. … He loves work – he’s most exuberant when we’re pounding on the book …”

Lewis and De Kruif changed vessels and sailed for England, where Lewis intended to draft the novel itself. By the time they docked, he had written a 60,000-word synopsis.

Soon after they reached England, Lewis flew into a rage at De Kruif for the disloyal act of taking a trip with Rhea to visit relatives. Lewis quickly apologized and their working relations resumed. But De Kruif had had enough of the writer’s craziness, and the friendship faded.

Lewis was well aware of what he owed De Kruif. “It’s going to be my best book,” he told Mencken, “though it isn’t just mine by a long shot.”

It took the novelist a year and change to complete the manuscript.

As publication approached, De Kruif asked Harcourt and Brace to include a line under Lewis’s name on the title page: “In collaboration with Paul H. De Kruif.” Either the publishers or Lewis said no, whereupon De Kruif asked that his role not be mentioned in the book at all.

But Lewis countered by drafting this acknowledgment: “I am indebted not only for most of the bacteriological and medical material in this tale but equally for his suggestions in the planning of the fable itself  – for his realization of the characters as living people, for his philosophy as a scientist.” De Kruif proposed help in place of suggestions; Lewis agreed. 

Through the years, a few would whisper that Paul De Kruif actually had written Arrowsmith. “Nothing could be farther from the truth,” De Kruif attested in his memoir, as he did to anyone who raised the question. “Sinclair Lewis wrote it.”

Lewis’s biographers agree, with due credit to the uncredited scientist. “Egos aside,” writes Richard Lingeman, author of the most recent full biography, “the historian can safely say: Lewis unquestionably wrote every word of Arrowsmith; he could never have written it without De Kruif.”

Arrowsmith had no sooner been published than speculation arose about its chances for the Pulitzer Prize in fiction. For Sinclair Lewis, that was a sore point.

Four years earlier, in 1921, the committee appointed to name the winner of that year’s Pulitzer had chosen Lewis’s Main Street. But the judges were overruled by the trustees of Columbia University, who oversee the Pulitzers and thought Main Street failed to meet the Pulitzer standard  – that the winning novel must represent “the wholesome atmosphere of American life, and the highest standard of American manners and manhood.”

Lewis declared that if he ever won the prize for another novel, he would send it back.

Now came word that Arrowsmith had indeed won the Pulitzer. True to his vow, Lewis told Harcourt and Brace he was turning down the prize. The publishers urged him to hold off for a day or two to maximize publicity.

Lewis recognized that by the terms of the Arrowsmith contract, a quarter of the Pulitzer winnings would have been Paul De Kruif’s. So he offered his ex-friend an extra $250 from the book’s royalties.

De Kruif said thanks, but no. He was already banking plenty of his own royalties.

* * *

After parting from Lewis in England, the De Kruifs had returned to the United States, where Paul pitched Harcourt and Brace on the idea of a book about the pioneers of microbiology. The average scientist could never expect to find a broad audience for such a work. But the publishers decided to give De Kruif a tryout, thanks to his zeal for the project, his apprenticeship to a master storyteller and Lewis’s endorsements of De Kruif as a coming talent.

The book that resulted, Microbe Hunters (1926), swiftly sold 100,000 copies and kept going, vaulting De Kruif into the second career he had envisioned as a fulltime writer explaining science to a mass audience.

Writing mostly at his and Rhea’s home in Holland, Michigan, he published 13 books in all  – including one with Rhea and a memoir, The Sweeping Wind  – and dozens of articles. He also gave his name and time to public health campaigns. He died in 1971.

Microbe Hunters is still read as a minor classic of its genre  – works of nonfiction that borrow the dramatic tools of the novelist to tell an absorbing true story. Indeed, the lively sales of Microbe Hunters helped to show publishers that readers were eager for books about the secret worlds uncovered by scientific research, and equally fascinated by the scientists themselves.

Many books following De Kruif’s model would be widely read from his time to our own era, with critical praise and prizes for the likes of Richard Rhodes’s The Making of the Atomic Bomb (1987); Sylvia Nasar’s A Beautiful Mind (1998) about the mathematician John Forbes Nash; and Elizabeth Kolbert’s The Sixth Extinction (2014), about the imperiling of species by climate change and habitat destruction.

* * *

After Arrowsmith Lewis wrote many more novels, but only two or three, according to critics, met the standard he had set with Main Street, Babbitt and Arrowsmith. Those built the reputation that brought Lewis the Nobel Prize in literature in 1930. That one he accepted.

Arrowsmith itself still resonates. Its themes echo in contemporary debates about the relative merits of movements for “evidence-based medicine” and “patient-centered care.”

And as a novel it is still read and loved, especially among readers whom it inspired to take up careers in medicine and science.

Dr. Howard Markel, a pediatrician, historian and author of his own popular books about medicine  – not to mention the George E. Wantz Distinguished Professor of the History of Medicine and director of the Center for the History of Medicine at U-M  – has remarked often on Arrowsmith‘s enduring value.

“My battered paperback copy of Arrowsmith is annotated throughout with the same pen-scrawled comment: ‘Still true!'” Markel wrote in 2001. “I am hardly alone: from its publication to the present, countless men and women have been inspired to pursue careers in research because of Martin’s intense devotion to science. Indeed, it would be a fascinating … study to survey physicians, medical scientists, and public health workers whose career paths were directed by Martin Arrowsmith …”

Sources included Sinclair Lewis, Arrowsmith (1925); Paul De Kruif, A Sweeping Wind (1962); James M. Hutchisson, The Rise of Sinclair Lewis, 1920-1930 (1996); Richard Lingeman, Sinclair Lewis: Rebel from Main Street (2005); Mark Schorer, Sinclair Lewis: An American Life (1961); Howard Markel, “Reflections on Sinclair Lewis’s ‘Arrowsmith’: The Great American Novel of Public Health and Medicine,” Public Health Reports 116:4 (July-August 2001); Robin Marantz Henig, “The Life and Legacy of Paul De Kruif,” Alicia Patterson Foundation (2002); and Powel H. Kazanjian, Frederick Novy and the Development of Bacteriology in Medicine (2017).