By the early 1920s, Sabin was well into her research on the origins and functions of the white blood cells called monocytes and was yearning to have more time for that work. She was very happy at Johns Hopkins, despite the disappointment over the Anatomy Department chair, but as a faculty member was obliged to divide her time between teaching and research. In late 1923, Simon Flexner, Director of the Rockefeller Institute for Medical Research, and a longtime admirer of Sabin's work, suggested that she consider joining the institute's staff and head its new Department of Cellular Studies. "Something fundamental should be done about the anemias and leukemias," he said, "and you are the best person to do it." After some consideration, Sabin accepted, on the condition that salaries for several of her Hopkins lab fellows be included. She began her work at the Institute in September 1925.
The Rockefeller Institute for Medical Research had been established in 1901 to support intensive scientific research in medicine, especially infectious diseases. Although laboratory science had become an increasingly important source of medical knowledge and therapeutics, it was not well-supported in most late nineteenth-century American colleges and universities. Nor, prior to the Rockefeller Institute's founding, did the United States have any counterpart to the Pasteur Institute in France and the Koch Institute in Germany, which were established in the 1880s. Following the example of the European institutes, the Rockefeller Institute recruited the best scientists, and provided them with comfortable stipends, well-equipped laboratories, and freedom from teaching obligations and university politics, so that they could devote their energies to research. For Sabin, this was an ideal situation.
In New York, Sabin led a group of younger investigators, and continued her studies on the role of the monocyte and other white blood cells in the defense of the body against infections. Sabin's team participated in an inter-institutional program organized by the National Tuberculosis Association's Medical Research Committee to integrate bacteriological, chemical, and biological studies being carried out in pharmaceutical companies, universities, and federal and private research institutes. These research efforts, between 1925 and 1938, yielded a much better understanding of the disease.
In tuberculosis, the causative organisms (usually Mycobacterium tuberculosis or Mycobacterium bovis) provoke the immune system to form lesions called tubercles. These lesions are composed of layers of immune system cells, including macrophages, mononuclear cells (mostly lymphocytes), and giant multinucleate cells, surrounding a center of cell debris. In humans, these lesions usually manifest in the lungs, but they can also form in other body tissues, depending on how the infection is acquired and how virulent the bacteria strain is. Tubercles, like abscesses, are the body's way of walling off poisonous microorganisms. However, their formation damages the surrounding tissue, and compromises its normal functioning. And because the bacteria sometimes remain alive within the tubercle, they can be released back into the tissue if the tubercle breaks open, thus starting the infection process anew. Since the 1890s, researchers had known that the characteristic cellular reactions to these bacteria also could be produced by dead tuberculosis bacteria cells. This suggested that some component of the bacterial cells themselves had a role in the tissue reactions. Sabin and her collaborators hoped that, by elucidating the relationship between the tuberculosis bacteria chemistry and the immune responses to it, a way could be found to interfere with tubercle formation and thus arrest the destructive process. This approach, while it did not ultimately produce a cure, generated much new knowledge about the tuberculosis infection process and about immune system function.
For the National Tuberculosis Association project, standard strains of tuberculosis bacteria were grown in large quantities on synthetic media by pharmaceutical manufacturers H. K. Mulford and Parke, Davis. They were then analyzed chemically by Rudolph Anderson and others at Yale University. Sabin and her co-workers then tested the individual chemical components on laboratory animals and observed a variety of effects. For example, several of the lipids (fats) gave reactions resulting in tubercle-like groups of immune cells. Waxy components stimulated the proliferation of fibrous tissue. Tests with lipid components also showed that certain fatty and wax-like substances could be identified within the bacteria-ingesting immune cells (including macrophages and monocytes), a finding that made it possible to determine which cells reacted to each substance and to observe how the cells dealt with the materials.
In these investigations, Sabin also discovered how immune system cells such as monocytes evolved into more specialized cells. For example, monocytes, as they ingested one bacterial component, were induced to mature into epithelioid cells. These cells, in turn, usually arranged themselves into tubercles. Characteristic "giant cells" often then developed from the epithelioid cells. These cells did not return to monocyte form after dealing with the bacterial component, but remained in their altered form.
Sabin's last research project at Rockefeller was inspired by these findings that monocytes took up certain components from tuberculosis bacteria. She spent her last years there investigating how antibodies were formed in response to foreign substances. For this she used a new protein-bound red dye, developed by Rockefeller colleague Michael Heidelberger, as a tracer antigen.
Throughout this period, Sabin also embraced life in New York City: she enjoyed the theater, concerts, museums, dinner parties, and lively discussions with a large circle of friends, which always included colleagues and co-workers. Her correspondence reveals that her delight in these activities was equal to that in her research work, and her former students and research colleagues valued her social and cultural companionship fully as much as her scientific brilliance.