As the nineteenth century gave way to the twentieth, the dramatic revolution in microbiology engendered by the work of Pasteur, Koch, and their disciples began to translate into advances in medicine. In the United States, nowhere was this more evident than at Johns Hopkins in Baltimore, the home of Osler and other giants of early, modern medicine. The medical school there was founded in 1893 with William Welch as its inaugural dean, and it rapidly became the breeding ground for America’s best-trained physicians. However, the burgeoning epicenter of medical research in the United States would be the newly created Rockefeller Institute, located on an isolated, windswept vista on the Upper East Side of Manhattan. There, the mysteries of disease would begin to be unraveled, leading to rapid advances in the therapeutic approach to many illnesses including a number of the most important bacterial infections of the time—meningococcal meningitis among them.

The national unification engendered by the conclusion of the Civil War allowed the extension of Northern industrialization to the rest of the country. For ambitious, industrious, self-made young men like Andrew Carnegie and John D. Rockefeller, it represented a fertile opportunity for advancement. Around the same time period that Koch proved a microbial etiology of tuberculosis and Pasteur demonstrated the efficacy of a rabies vaccine in humans, Rockefeller’s company—Standard Oil—was refining more than ninety percent of America’s oil.¹

As Rockefeller’s capitalistic success grew, so did his philanthropic activities. No doubt much of this part of his personality derived from his strict Baptist upbringing. He contributed generously to a variety of charitable causes, many of them aligned to priorities within the Church, including hospitals and public welfare projects. By the last decade of the nineteenth century, his annual contributions were worth hundreds of millions of dollars in today’s currency value. He needed a deputy to manage just the philanthropic side of his business activities. In 1889, he would meet a cleric who would do just this—and help him change the course of medical history.

Reverend Frederick T. Gates, executive secretary of the American Baptist Education Society, had risen meteorically from his upbringing in rural poverty through ministerial work in Minneapolis, to a position of statewide leadership among Minnesota Baptists. His success was a testament to both his personal attributes and his flair for fundraising. His appointment as essentially a development officer in the Baptist national Education Society placed him in the circles of some of the wealthiest men in the country. Perhaps the most prominent of these individuals—Rockefeller—was so impressed with Gates’ financial and analytic prowess that he gave him stewardship over all of his non-Standard Oil related investments as well as his philanthropic activities.

By the end of the nineteenth century, Gates was working primarily with John D. Rockefeller, Jr. on the philanthropic side of the Rockefeller financial empire; Junior had joined the family business after graduating from Brown in 1897. That same year, according to Gates’ own retrospective account of the origins of the concept of the Rockefeller Institute of Medical Research, the Reverend became aware of the vast deficiencies in medical science as compared with the natural sciences; he envisioned an institution in which physicians could investigate important scientific questions unencumbered by the demands of a clinical practice. Although he had observed the shortcomings in medical education while serving as a pastor tending to the sick and interacting with physicians during his tenure in Minneapolis in the 1880s, his personal epiphany regarding the many gaps in medical knowledge of the era apparently stemmed from a thorough reading of Osler’s Principles and Practice of Medicine—most likely the second edition of this definitive text—while vacationing with his family in the Catskills.

Gates’ boss was also inclined towards medical philanthropy. The senior Rockefeller had always taken an interest in medicine—homeopathic medicine—presumably borne from early childhood memories of his grandmother’s herbal remedies prepared from a “physic bush” in their backyard in upstate New York.² Throughout his life, Rockefeller maintained an appreciation for homeopathic medicine and in fact, insisted that it be equitably represented in his philanthropic activities. This remained a chronic, simmering debate within the dynasty.¹

As with many investments made by Rockefeller during his long, successful career, timing was critical, and the timing for medical philanthropy in turn-of-the-century America was ripe. In the two great medical science capitals of Europe—Paris and Berlin—research institutes had been established for their most prominent national figures in this arena—Pasteur and Koch, respectively. Private benefactors had built the Pasteur Institute; the Prussian government had supported the Koch Institute for Infectious Diseases.

In the United States, advances in medical science were closely allied with those in medical education. Practitioners for whom medicine was an occupation and teaching it was an uncompensated chore had stunted the development of medical education under a long tradition of on-the-job apprenticeship training of would-be physicians. This situation began to change in the latter part of the nineteenth century with reform and reorganization of some of the nation’s oldest and most prestigious medical schools such as Harvard, Penn, and the University of Michigan—much of it facilitated by faculty members returning from scientific training in the venerable laboratories of France, England, and most notably, Germany.

The first and truest union of medical education and research with clinical medicine occurred with the opening of the medical school at Johns Hopkins University in 1893, a defining moment in the rise of modern American medicine. The hospital, founded by an 1873 bequest from Johns Hopkins, an entrepreneur who had made much of his substantial fortune with the Baltimore and Ohio Railroad, opened its doors in 1889 with such luminary Department Chairs as Welch in Pathology, Osler in Internal Medicine, and Halstead in Surgery.³ Four years later Welch, himself trained in Koch’s laboratory in Berlin, was the first Dean of the new medical school and had organized it into its preclinical departments, each with laboratories directed by trained scientific investigators and with full-time clinical faculty directing the hospital’s clinical areas.⁴

Gates’ vision of a research facility in which the best and brightest medical scientists could creatively explore the fundamental, scientific questions related to a broad range of diseases was analogous to the Hopkins model for medical education. To allow for the uninterrupted pursuit of medical research, investigators would work without concern for economic pressures—the faculty of the institute would be fully salaried—or teaching duties. Initially, the institute was organized without a university affiliation largely for this reason, although the decision was also influenced by the importance of avoiding a slight of homeopathic medicine. Rockefeller Sr. was, after all, a lifelong proponent of homeopathic medicine, and it was understood that the existing scientific medical universities were the purview of the elite, ‘regular’—allopathic—physicians.¹

Gates initially proposed the formation of an American institute, similar to the Pasteur Institute in Paris, in a memo to his boss in July 1897. As was Rockefeller’s habit, probably gleaned from maternal lessons internalized at a young age, he tended to allow issues to “simmer” before returning a decision.² During this time, the ensuing four years, Gates and Junior performed their own due diligence towards their now shared goal; a consultant was hired to study and report on European models of such institutes, and medical experts were debriefed and encouraged to weigh in on the potential importance of such an undertaking to the advancement of medical science. The death of one of Rockefeller Senior’s grandchildren in early 1901 of scarlet fever—a disease of unknown cause and for which there was no effective therapy at the time—tragically illustrated the need for the kind of research efforts proposed for the Institute. This event may have ultimately helped to crystallize Senior’s decision to fund Gates’ grand vision.

In June 1901, the Rockefeller Institute opened for business, largely as a grants organization in temporary quarters over its first few, formative years. Welch, then dean at Hopkins and widely considered the major force in American medical science of the era, was recruited to help organize the new Institute and to serve on its first Board of Directors. It was on his recommendation that his friend and colleague Simon Flexner, one of his former pathology trainees at Hopkins, was selected to the Board; Flexner subsequently became the inaugural Director of the Institute’s laboratories. By 1904, the laboratories within the Institute had begun their own research programs, generously supported by Rockefeller.⁵

Flexner was one of nine children of German-speaking Jewish parents reared in penury in Louisville, Kentucky.⁶ Flexner’s early life failed to presage his later accomplishments; he dropped out of school at the age of 14 and was directionless through his teenage years until a brush with death due to typhoid fever seemed to ignite a sense of intellectual purpose in him. After an apprenticeship with a local pharmacist, he clerked in his older brother’s drugstore and there, through observing discussions of cases between physicians, became interested in medicine.

Because most medical education in the United States even in the late nineteenth century was still purely didactic and provided by local practitioners, Flexner arranged to attend a series of clinical lectures—at reduced fees due to his limited financial circumstances—and subsequently received a medical degree from the University of Louisville in 1889. In 1891, he began a fellowship in pathology and bacteriology, both new educational initiatives in select U.S. hospitals, under the tutelage of Welch, the Chair at the newly minted hospital at Johns Hopkins. When Hopkins opened its Medical School two years later, Flexner was given a faculty appointment in pathology.