As Americans were becoming progressively more deeply involved in Vietnam, first as “advisors” but subsequently in the mid-1960s as full-fledged combatants, the Army Medical Department was developing plans and organizing health priorities in order to fulfill its mission to “conserve the fighting strength.” As we have seen, outbreaks of meningococcal meningitis had occurred during both world wars, and the disease remained a significant cause of mortality and lost duty time among recruits at basic training sites in the U.S. in between wars. Additionally, meningitis was known to occur worldwide in both its epidemic and sporadic forms, making it an ongoing health threat wherever the military might deploy in the future.

Because of these concerns, the Army Medical Department made the strategic decision to direct a focused component of its broad research activities in communicable diseases and preventive medicine towards solving the problem of meningococcal meningitis. The staging ground for this work would be at ‘command central’ for such research in the Army—the Walter Reed Army Institute of Research in Washington, D.C.

Walter Reed General Hospital—built on the site from which Confederate General Jubal Early had attacked the nation’s capital in July 1864—opened its doors to ten patients in May 1909. As the namesake of the recently deceased Army officer who had presided over the landmark studies on yellow fever transmission in Cuba, it boasted an 80-bed capacity and the distinction of being the first, named, permanent, Army general hospital.¹

Sixteen years earlier, in 1893—the same year that Simon Flexner received his first faculty appointment in pathology at Johns Hopkins—Army Surgeon General George Sternberg had established the new Army Medical School on the grounds of the Army Medical Library and Museum in the Southwest quadrant of Washington, D.C.² Sternberg, widely considered to be the founding father of American bacteriology, had independently isolated—along with Pasteur—the pneumococcus in 1881, thus endowing him with indirect ties to polysaccharides and the meningococcal vaccine research that would occur nearly a century later within the organization he created.

The Medical School would move to the northern edge of Washington—to the tree-lined, Takoma Park campus of Walter Reed General Hospital—in 1923. Twenty-eight years later, the hospital and medical school would be officially combined to form the Walter Reed Army Medical Center. In 1953, the medical school ceased to exist as a functioning unit; its research components, housed in the large, H-shaped building 40 on the grounds of the Medical Center, became the Walter Reed Army Institute of Research—WRAIR.

WRAIR and its Army Medical School predecessor already enjoyed a storied scientific history at the time that research on meningococcal vaccines began in earnest there in the latter part of the 1960s. Within its stated mission involving public health and prevention of disease and its inherent global perspective, the list of important medical achievements that derived from that single institution during its first seventy years of existence was unparalleled.

In the early years, before moving to the grounds of the hospital, WRAIR researchers were responsible for significant advances in preventive medicine. The investigations of the Typhoid Board in 1898 and those of the Yellow Fever Commission in Cuba two years later, both commissioned by Surgeon General Sternberg and headed by an Army physician—Major Walter Reed—established critical epidemiologic features of these two diseases, allowing for their eventual control among troops by vaccination. Following these efforts, Major Frederick Russell introduced mass typhoid vaccination of soldiers in 1909. Major Carl Darnell pioneered the use of chlorine to purify drinking water in 1910—forming the basis for future water purification technologies. Lieutenants Charles Craig and Percy Ashburn had proven the viral etiology of dengue fever—a severe tropical infection—in 1907; twenty years later, Colonel Joseph Siler demonstrated that the disease was mosquito borne. And Colonel Edward Vedder showed that the nutritional deficiency affecting peripheral nerves and the heart—beriberi—caused by a lack of vitamin B₁ in the body, can be prevented or treated by ingesting rice bran extract. When the new WRAIR building was completed on the grounds of Walter Reed in 1932, its four named pavilion wings—Sternberg, Vedder, Craig, and Siler—paid homage to some of these early accomplishments.

Because of the importance of communicable diseases to the health of U.S. military members and their dependents, much of the focus of WRAIR’s research was trained on these issues. Microbiologist Maurice Hilleman, who would later go on to Merck where he would work for more than 45 years and be responsible for developing and licensing more human vaccines than any other scientist in history, isolated the virus—later named adenovirus—that caused the majority of seasonal, acute respiratory disease outbreaks in military recruit centers.³ Both Hilleman, and later Ed Buescher—Director of the Division of Viral Diseases—spearheaded successful adenovirus vaccine research at WRAIR. In 1961, Buescher’s research team, comprising two young Army physicians, Malcolm Artenstein and Paul Parkman, was one of two groups in the U.S. to simultaneously and independently isolate the rubella virus—the cause of German measles—from patient samples. Their work would lead to the development of an effective, licensed rubella vaccine within a decade. The next great challenge for WRAIR researchers would be to find a way to prevent epidemic meningitis among troops.

The specter of recurrent, epidemic meningococcal disease at military basic training sites—beginning to bustle by the early 1960s with renewed activity in preparation for escalating efforts in Vietnam—was a compelling concern of military planners. Beginning during World War II, short—three-day—courses of the antibacterial drug sulfadiazine were used to prevent meningitis in military recruit camps. The drug worked by eradicating the meningococci from their temporary homes in the noses and throats of soldiers; without carriers, the germ was not passed from one recruit to another—thus, profoundly limiting the opportunity for epidemic disease to ignite. However, as we have seen, within two decades—by the early 1960s—meningococci had become progressively more resistant to the effects of sulfa drugs. This, combined with the increasingly common reports of outbreaks of antibiotic resistant meningococcal meningitis within the U.S. and abroad, intensified the apprehension of military commanders.

A series of highly publicized outbreaks in the U.S. through the early 1960s heightened their discomfort. Distinct but nearly concurrent epidemics of sulfa-resistant group B meningitis occurred at both Army and Navy recruit facilities in California in 1963.⁴ The next year, an outbreak at Fort Ord—a massive Army training camp south of San Francisco that housed nearly 30,000 recruits at a time—resulted in 104 cases of meningococcal disease.⁵ Most of these occurred in combat trainees, but ten of them affected civilian military dependents; fourteen of these patients died, two of the civilians among them. The Fort Ord outbreak led to such negative press and near “hysteria” in the surrounding communities that the Army was forced to temporarily suspend basic training there—an almost unheard of event in the military.

The impact of these episodes—magnified by further outbreaks among both military and civilian groups in the U.S. and abroad—convinced the U.S. military command that a focused effort against the meningococcus by the Army Medical Department was necessary. Prevention—WRAIR’s specialty—was the last best hope, and this meant the development of a meningococcal vaccine. To attain this goal would require a well-reasoned, informed, logical, and organized experimental approach that would draw upon a half century of immunochemistry and polysaccharide research. Buescher knew just who to turn to for this critical project.

Malcolm Artenstein, like most eligible members of the class of 1955 at Tufts University Medical School in Boston, was drafted into the Army. After residency training in internal medicine and a research fellowship in the fledgling discipline of infectious diseases with Louis Weinstein—the prototypical physician–scientist and master teacher in the field—he was called to active duty in 1959. At Fort Sam Houston in Texas, the place where every physician underwent basic training in those days, he was singled out—rarely a positive in the Army—for his infectious diseases credentials and thus brought to the attention of Buescher at WRAIR, who was looking for young talent. Buescher had already been made aware of Artenstein through a conversation with Lou Weinstein. This was a fortuitous occurrence for the young conscript, likely saving him an assignment to some desolate Army clinic or remote field hospital.

Upon arrival at WRAIR, Artenstein immediately became involved in the work on the rubella virus there, culminating in the first report of its isolation.⁶ His two-year military obligation ended and never feeling entirely comfortable in uniform—he would cross the street to avoid having to return the salute of enlisted ­soldiers—Artenstein returned to civilian, academic medicine with Dr. Weinstein in Boston. But this was to be short lived; in 1962, at the age of 32, he was back at WRAIR—as a civilian—after accepting an offer from Buescher that was too good to pass up to be first the Assistant Chief of the Department of Viral Diseases and then, in 1966, the Chief of the Department of Bacterial Diseases. He would remain there for the rest of his brief, but highly productive career.

In those early years back at WRAIR, Artenstein’s research focused on viral infections of the respiratory and nervous systems and on mechanisms of immunity against viruses. In 1966, he started working on meningococcal disease. In short order, this work became his singular focus and kept him in the laboratory at least six days during most weeks and reviewing data at home at night. Artenstein was a thoughtful, methodical, yet creative researcher who understood the importance of building and nurturing a strong research team in order to answer the important scientific questions. He had a keen ability to “ask the crucial questions, obtain the critical data, and analyze it objectively”—quickly grasping the potential implications of experimental findings and then designing and executing the appropriate investigations to advance the studies.⁷