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In 1873 the chair of geology at the University of Cambridge fell vacant following the death of Adam Sedgwick. Nine candidates stepped forward, hoping to fill the post. The correspondence generated in the ensuing battle illuminates two areas of particular interest. First, the strategies hidden behind bland lists of successive professors: candidates, peers and patrons manoeuvred to influence the outcome of the competition and competitors tried to reinforce their geological respectability by collecting testimonials from estimable geological acquaintances. Second, the Woodwardian competition inspired some outspoken opinions from British geologists about the relative worth of the candidates, which offer a fresh perspective on the process of professionalization in nineteenth-century science. The applicants came from various backgrounds, including gentlemanly amateurs, clerical geologists, Survey geologists and professors. Judging from the opinions of their peers, it seems that a non-professional or clerical status was rarely of primary concern in defining geological respectability at this time.
With the development of a mature institutional identity in the 1960s, cell biology joined the ranks of the biological disciplines. Although its roots were interdisciplinary, I have described how it developed into a distinct and enduring discipline. A critical element in this achievement was that it deployed new research techniques, especially cell fractionation and electron microscopy, which enabled its practitioners to explore mechanisms that were inaccessible to existing disciplines such as cytology and biochemistry. Using these tools the pioneers in cell biology, sometimes in collaboration with biochemists and molecular biologists, developed mechanistic explanations of numerous cell functions at multiple levels of organization. The discovery of these mechanisms, as described in Chapters 5 and 6, exemplifies the project of explaining phenomena mechanistically that I presented more abstractly in Chapter 2.
Cell biology, like any discipline, continues to develop and adjust its niche relative to other disciplines. It is most distinctive in (1) the attention it gives to variations in structure and function across cells from different organs and organisms; and (2) its status as an interdisciplinary nexus in which findings from physical, chemical, developmental, and other types of investigation are integrated toward an overall goal of understanding the cell. The emphasis given to different contributing disciplines has changed over time, however. In the 1950s and 1960s, collaborations with biochemists were of crucial importance. More recently, cell biology has drawn closer to molecular biology.
In previous chapters I have focused on how new research techniques, especially electron microscopy and cell fractionation, made it possible for researchers to investigate mechanisms within cells. I have analyzed the development of the first products of these investigations – mechanisms for oxidative metabolism in the mitochondria, for protein synthesis in the endoplasmic reticulum, for protein transport in the Golgi apparatus, and for breakdown and disposal of cellular material in the lysosome. These endeavors were the focus of a new field of science that by the 1960s called itself cell biology. Many researchers chose this term intentionally to mark a distinction between classical cytology, concerned primarily with morphological structure, and the new, initially interdisciplinary enterprise that took on the challenge of integrating structural and functional information about the cell. By the end of the 1960s, this new scientific field had successful occupied the terra incognita between cytology and biochemistry I identified in Chapter 3.
To become more than a temporary enterprise, cell biology needed its own institutional identity. Journals and professional societies are among the defining institutions of a scientific discipline. These provide important channels for scientists not only to disseminate their work, but also to receive credit for it. Publishing in a journal or appearing on a scientific program provides stature to scientists and evidence that their work is recognized by peers. Such institutions, though, play more than a certifying role.
… is our method of fractionation like the clumsy undertaking of a car mechanic who attempts to use his crude tools to analyze a watch? I believe that it is almost as bad as that. Nevertheless, we have no alternative and must hope that our tools will become refined as we proceed in the analysis. Meanwhile we have to look out for the signs that guide us in the right direction; we must try to correlate the experimental findings obtained with cell-free systems with the complex physiology of the cell; we must keep in view the metabolic ‘Gestalt’ of the cell; and finally, we must ‘seek simplicity and then distrust it.’
(Racker, 1965, p. 89)
“Seeing is believing.” So we are often told. You do not, however, have to go far to find instances in which seeing is misleading. For example, look at Figure 4.1 and ask yourself whether the shaded surfaces of the two figures are identical in shape. If you are like most people, you will judge that the shapes differ – one long and narrow, the other closer to square. However, you can convince yourself that they actually have identical dimensions if you rotate one of them 90 degrees and measure the corresponding sides. Your visual system misled you in this case about what actually exists in the world, creating what scientists refer to as an artifact (or artefact, especially in older publications).
This continuous body of knowledge, which should be properly named cellular and molecular biology, could be compared to a bridge which, like its equivalents in civil engineering, has two bridgeheads: one in traditional anatomical-morphological sciences and the other in equally traditional biochemistry. The cautious and careful have stayed close to the bridgeheads because the area around them had been consolidated over centuries by the work of their predecessors. The bold and venturesome have ventured on the bridge itself from both directions, because they believed that there was where the action was going to be…. As in the old Latin proverb, fortune favored the bold: the bridge proved to be strong enough to support the intense occasionally frantic activity of whole armies of explorers.
(Palade, 1987, pp. 112–13)
In the 1950s and 1960s the initial ventures into the terra incognita between classical cytology and biochemistry developed into the robust bridge Palade identified in the above quotation. In large part this involved building on the localization of cellular energetics in the mitrochondria, and of protein synthesis in the microsomes, that had been established in the 1940s by decomposing these organelles and figuring out the operations associated with their parts. I will focus principally on these developments, but in the 1950s investigators identified the function of two other organelles – the Golgi apparatus and the lysosome – and established research programs to determine how they performed their functions.
I do not in the least mean by this that our faith in mechanistic methods and conceptions is shaken. It is by following precisely these methods and conceptions that observation and experiment are every day enlarging our knowledge of colloidal systems, lifeless and living. Who will set a limit to their future progress? But I am not speaking of tomorrow but of today; and the mechanist should not deceive himself in regard to the magnitude of the task that still lies before him. Perhaps, indeed, a day may come (and here I use the words of Professor Troland) when we may be able ‘to show how in accordance with recognized principles of physics a complex of specific, autocatalytic, colloidal particles in the germ cell can engineer the construction of a vertebrate organism’; but assuredly that day is not yet within sight of our most powerful telescopes. Shall we then join hands with the neovitalists in referring the unifying and regulatory principle to the operation of an unknown power, a directive force, an archaeus, an entelechy, or a soul? Yes, if we are ready to abandon the problem and have done with it once and for all. No, a thousand times, if we hope really to advance our understanding of the living organism.
(Wilson, 1923, p. 46)
The focus of this book is creation of cell biology in the mid-twentieth century as a distinct field of biology devoted to discovering and understanding the mechanisms that account for the ability of cells to live.
This book is the product of research spanning two decades. In the 1980s I had been investigating the history of cytology in the nineteenth century and biochemistry in the early twentieth century when I responded to an announcement from the American Society for Cell Biology of a fellowship for support of research on the history of cell biology. With their financial support in 1986 and 1987 I began to examine the creation of modern cell biology in the decades after World War II. I am enormously grateful not only for the fellowship funding but also for the invaluable assistance of individuals associated with ASCB. In particular, I thank Robert Trelstad, then Secretary of ASCB, who invited me to society and executive council meetings, gave me encouragement, and provided entrée to senior members of the society. A number of the founders of modern cell biology were still active in the society and I had the opportunity to meet and interview them regarding their own contributions to cell biology and their recollections of the early days of this field. I also had access to the archives of the society, which were then housed at the Society offices. (They have since been transferred to the University of Maryland, Baltimore County.) I have relied heavily on this material in analyzing in Chapter 7 the history of the American Society for Cell Biology.
In the early 1990s I received additional support from the National Endowment for the Humanities.
In order to succeed in solving these various problems, one must so to speak progressively dismantle the organism, as one takes to pieces a machine in order to recognize and study all its works.
(Bernard, 1865, Part II, Chapter 1)
A different kind of science
To many people, cell biology is an unlikely domain to impart impetus for a major shift in the way philosophy of science is practiced. Cells appear to be the object of straightforward empirical observation, not of bold theories that challenge the status quo. In high school or at the museum you look into the microscope and struggle to see what you are told you should see – structures that are never as sharp and well delineated as in the drawings in textbooks. What could cell biology be but a tedious descriptive science? This popular conception, however, is quite erroneous. Cells, as Theodor Schwann first concluded in the 1830s, are the basic units of life. They perform all essential vital functions: extracting energy and building materials from their environment, constructing and repairing themselves and synthesizing products for export, regulating their own internal operations, reproducing themselves periodically by dividing, cleaning up their own waste, and so forth. Beginning in the 1940s an initially small cadre of investigators who were pioneers in the modern discipline of cell biology began to figure out the biochemical mechanisms that enable cells to perform these functions.