by Joseph Luna
The birth of a scientific field often combines new technology with bold hypotheses, unexpected collaboration, and a healthy dose of luck. There’s also time, that ultimate arbiter of the significant, upon which a new field grows and matures, from puzzling first glimpses to textbook diagrams and beyond. Increasingly in today’s world, inhabited by 90% of all the scientists who’ve ever lived1, the pace has quickened, but the basic arc remains the same: new tools are seized upon with fresh minds, and the results are often breathtaking.
The story of modern cell biology in the twentieth century presents a fascinating case study of this trajectory, considering the strides made by its predecessor, cytology. Tracing a direct route from van Leeuwenhoek’s first microscope to Hooke’s descriptions of cork (from which the term “cell” was coined) in the seventeenth century, cytologists by the 19th century had the impression that cells were worlds unto themselves, with analyses of visible structures such as mitochondria, golgi bodies, and nuclei, and with microscopic descriptions of processes such as cell division. But by the early twentieth century, the resolving powers of the light microscope had reached their limit, and the study of the fine structures of cells remained out of reach, if they existed at all. There wasn’t much to counter the argument that while cells were the basic units of life, they were largely devoid of subcellular structure.
Entering an Unseen World: A Founding Laboratory and Origins of Modern Cell Biology 1910-1974, written by Steinman lab Senior Research Associate Carol L. Moberg, picks up the tale from here and tells the story of how everything changed, starting in 1910, and originating in one laboratory at the then newly created Rockefeller Institute for Medical Research. That was the year when James B. Murphy joined the laboratory of Peyton Rous to study cancer. Within a year, Rous published his famous discovery of an infectious sarcoma of chickens that upended traditional views of cancer as uncontrolled and spontaneous cell growth. Murphy disagreed with the viral cause of these tumors, as he could see no reason for some other stimulus to provoke cancer. This question, on the viral or chemical origin of cancer, divided the two researchers, who eventually drifted apart when Murphy was promoted and put in charge of his own laboratory. Part of what made Murphy’s doubt fruitful over the next two decades was that it forced him to ask an even more basic and heroic question: notwithstanding the cause of cancer, if its basis lay within the cell, then what precisely was inside the cell?
This line of thinking, to break cells open and study their normal structures, functions, and dysfunction during disease, formed the roots upon which cell biology formally sprouted in the 1940s, when Keith Porter and Albert Claude (members of Murphy’s laboratory) working with Ernest Fullam, applied the use of the electron microscope (EM) to study the fine structure of cells. Their first EM picture, one that graces the cover of this book, is widely cited as the formal genesis of modern cell biology. Yet while the proverbial “and the rest is history” may apply, Dr. Moberg refreshingly goes much farther beyond the narrative history of the young science to highlight the motivations that drove its key figures—Porter, Claude, and later George E. Palade—to invent, shape, and standardize the nascent field. For them and the many beyond living memory, Dr. Moberg’s expertise as a science historian pieces a comprehensive and detailed, yet readable and exciting, history. Combined with entertaining anecdotes from Porter, Claude, Rollin Hotchkiss, and others, the result is an immediate and human portrait of cell biology as a distinct Rockefeller creation.
This history is further brought to life in the second part of the book. Since 1995, Dr. Moberg has also assembled and edited an impressive roster of voices to tell the story of cell biology at RU in their own words. Often told in the first person, these histories offer a glimpse of Rockefeller amid the excitement of the 1950s through the 1970s, when the workings of many organelles were figured out under the “Palade model” of combining cell fractionation experiments to probe function, and EM to probe structure. And what a remarkable model it turned out to be: during this period were made the discoveries upon which a quarter of the university’s 24 Nobel prizes are based.
In this atmosphere, we journey with Christian de Duve to discover, purify, and characterize the lysosome in vivid detail. We witness James Jamieson, then a struggling 4th year PhD student, strike gold with an experiment that determined the direction of protein synthesis from the endoplasmic reticulum to the golgi apparatus and beyond. We get a glimpse of what it was like for Mary Bonneville, the first female graduate student of the university, to work with Porter and produce the Porter-Bonneville Atlas, a popular reference of all known EM structures at the time. Perhaps the most thrilling example, however, is Ralph Steinman’s account of the discovery of the dendritic cell—where the tools of cell biology proved decisive in allowing him to characterize DCs as the bridge between the innate and adaptive immune responses.
For biologists of all stripes, there is much to learn from these histories of a field maturing into an important and firmly grounded discipline within biology. And the tones of many of the contributors, while at times wistful, remain forceful in conveying the exhilaration of being at a beginning. Ultimately, this book is a celebration of great science, and a celebration of a principal scientific legacy of this university.
In his 1974 Nobel lecture, at the book’s thematic close, Albert Claude offered his view of the significance of the field he helped create. “We have entered the cell, the Mansion of our birth, and started the inventory of our acquired wealth.2” Entering an Unseen World presents a rich and inspiring history for all students of biology to inventory in one sumptuous volume. For this student, it is a poignant reminder of the Rockefeller University that was, and is.
1) David Goldstein—The Big Crunch (http://www.its.caltech.edu/~dg/crunch_art.html)
2) Albert Claude—Nobel Lecture: The Coming Age of the Cell. Nobelprize.org
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