To understand the development of the military-industrial complex in the second half of the twentieth century, we look back at the Manhattan Project that built the first atomic bombs during World War II. For biomedicine in the twentieth century, the U.S. antimalarial program serves a similar role. It was a dynamic, evolving, and inventive program that spanned some seven years (1939–1946). It changed how biomedical research and development (R&D) would be funded and organized in the postwar period. World War II was a watershed for science and technology. The atomic bomb, jets and rockets, radar, and penicillin were just...

Complex, amazing, and highly adapted: This is how a group of researchers at the National Institutes of Health described the parasites that cause malaria. These parasites were not just an admired object of research; they were an enemy to be respected and understood on their own terms. Through the development of synthetic antimalarial drugs in the first half of the twentieth century, malariologists, physicians, and chemists obtained critical knowledge of this successful foe. The scientific, medical, and natural-historical context of these novel pharmaceuticals emerged from earlier understandings of several essential elements: quinine and the cinchona tree from whose bark the...

The period between World War I and World War II was a productive one for antimalarial research. The first successful environmental insecticide, Paris green, was developed against mosquitoes. And on the drug front, new methods for testing antimalarials in animals—in birds, in fact—would emerge in the Bayer laboratories. These methods would persist as the backbone of antimalarial drug screening throughout the war and into the late 1940s. To appreciate the work done by the U.S. wartime antimalarial program, we need to understand the research tools available to it. What were the shapes and capabilities of model systems for...

Quinine—how to use it, make it, and especially replace it—remained a subject of much interest in the first half of the twentieth century. And with good reason. Although precise numbers on disease and disability were (and are) notoriously difficult to collect, especially for diseases like malaria that are at their worst among the world’s poorest, in 1926, the League of Nations estimated two million deaths per year from malaria. Since the death rate was three to four per 1,000 cases, this meant an estimated 650 million cases of malaria, or roughly one-third of the human race.¹ During the...

When the war in Europe began in September 1939, researchers and health officials in the United States were already trying to address the shortcomings and potential shortfalls of quinine, cinchona, and the existing synthetic antimalarials. This period prior to U.S. entry into the war showed some of the weaknesses and strengths of the National Research Council’s approach to scientific research. The NRC had begun to take an interest in malaria chemotherapy some months before the invasion of Poland. Meeting in Washington, DC, in April, NRC’s Division of Chemistry and Chemical Technology (Chemistry Division) asserted the need for, and committed itself...

The National Research Council’s fear—that the world might be cut off from its quinine supply if Java were seized by a hostile nation—became reality early in 1942. As the worst came to pass, the federal government would ramp up its involvement in malaria research in an aggressive but scattered fashion. The crisis was too soon upon the United States for any preformed plan of action.

Squeezed by U.S. trade sanctions, the Japanese advanced into Southeast Asia, toward Dutch colonial possessions in the East Indies. On their way, they attacked the centers of Western naval power in the Pacific:...

The war began to turn dramatically in favor of the Allies during 1943. The surrender of the German army at Stalingrad in February and the Allied invasion of Sicily in July were two indicators of this shift. With the postwar world clearly in their sights and the growing complexity of wartime research demanding more administration, government functionaries looked to new bureaucratic structures for the management and control of projects like the antimalarial program. They worked changes not just in scale, organization, and methods of drug development but in the values of science and the scope of government involvement in biomedicine....

The emergence of chloroquine as the first-line drug for malaria prophylaxis and treatment was the great medical accomplishment of the antimalarial program’s later years. Chloroquine’s path from a failed drug in the Bayer interwar program to a wonder drug of the postwar world merits attention in its own right and also illustrates the networks of relationships that evolved during the U.S. antimalarial program. For U.S. soldiers and marines, chloroquine would emerge from testing programs too late to impact combat operations. With chloroquine and the insecticide DDT, another wartime development, in hand, the old Ross-Koch public health debate about whether mosquitoes...

In November 1945, Paul F. Russell, a Rockefeller malariologist who had spent much of the war in the U.S. Army Medical Corps, addressed the annual meeting of the American Society of Tropical Medicine. He began with a lament for the horror and loss of war and a tribute to what had been done to advance science, technology, and medicine, especially with regard to malaria: “Man’s net losses from World War II are so enormous that it would be illogical indeed to refer to war-produced scientific advances as dividends or to point to them with thoughtless pride. Rather, such progress constitutes...