In 1939, Keith Porter moved from Princeton University, where he had been continuing his work in amphibian embryology, to the Rockefeller Institute for Medical Research, where he joined the laboratory of James B. Murphy. Murphy's laboratory at that time was heavily involved in a major debate over the possible "infectious origin of cancer (Oberling, 1961). Although Peyton Rous had demonstrated in 1911 that a cell-free extract from a chicken sarcoma tumor could produce tumors in healthy chickens, there still was wide-spread disbelief that this was a real mechanism for the origin of cancer. By 1939, Murphy had inherited a central role in carrying on the research of Peyton Rous, and had recruited Albert Claude to work on fractionating tumor tissues in hope of finding the nature of the tumor transmitting agent suggested by Rous' experiments. By the time of Porter's arrival at Rockefeller, Claude had succeeded in isolating and purifying an "active principle" from tumor filtrates using high-speed centrifugation. Further, Claude felt that this fraction contained a nucleic acid of the ribose type (RNA), analagous to the DNA found in the pneumococcal transforming agent studied by Oswald Avery, also at Rockefeller. Porter's first project in Murphy's laboratory was the study of the effect of various carconogens on developing embryos.

In carrying out these studies, Porter developed great skill in the manipulation of embryonic tissues, including methods for keepting the tissues alive and growing in vitro. This work was interupted when Porter, along with his wife, Elizabeth, contracted tuberculosis and had to spend considerable time in a sanatorium. Not to be kept out of the laboratory, Porter developed a collaboration at the sanatorium with Diran Yegian, studying various forms of the tubercle bacillus by light microscopy. Porter's critical eye for artifacts in microscopic preparations led him to investigate in detail some of the effects of methods of growing bacteria and of harvesting them for microscopic study. This critical approach to microscopy and its potential artifacts were to stay with Porter for all of his subsequent career, which turned out to be focussed on microscopy in various of its forms.

Upon return to Rockefeller in 1943, his studies became heavily involved in the study of cells in culture. Through a series of fortuitous events, Claude and Porter became aware of the possibility of studying cancerous and normal cells in the electron microscope, in hope of visualizing the cancer producing agent directly. The only electron microscope in New York City at that time was one operated by Ernest Fullam, at the Interchemical Corporation. Albert Gessler, director of research at Interchemical, believed that the electron microscope had more potential for the study of living tissues than just for the study of particulates in paints and other finishes, for which it was used most of the time. Even so, it was only at night, after the day's work was done, that Fullam could collaborate with Claude and Porter. In 1944, the first electron microcope images of cells prepared by Porter were made, using the Interchemical microscope, the model EMB manufactured by the RCA Company in New Jersey.

The earliest electron micrographs were of Claude's cell fractions, including mitochondria and his RNA-containing "microsome" fraction. The first pictures of cells made in the electron microscope were of fibroblastic cells grown in co-culture with neuroblastic cells. The goal of studying these cells still was as a means of discovering the mechanism of cancer transmission. Murphy was convinced that putting Claude's microsomes onto cultured chick cells would lead to a transformation of these cells to tumor cells, and he hoped that the process could be followed in the electron microscope if only it was possible to visualize the cells. Poter, aware that even bacterial cells were too thick for visualization of internal structures in the electron microscope, also was aware that his cultured cells were spread so thin near their margins as to be virtually invisible in the light microscope. In his own words, Porter wrote that "such diaphanous cells might be suitable for electron microscopy, at least in their thinner margins (Porter, 1987). Inded they were; and the first few images obtained of the thin margins of these cells changed the course of Keith Porter's life and of biological science itself: the field of cell biology was born! Again in Porter's own words "we were the first...to see particles, to see structures that the light microscope had been unable to resolve." Of particular note was a fine, reticular network, confined particularly to the endoplasm of the cells, which soon became known as the endoplasmic reticulum.

Note: this review of early cell biology is based, in part, on an article by Carol L. Moberg of The Rockefeller University published in the Journal of Experimental Medicine, vol. 181, pp. 821-837, 1995.