Visions of Cell Biology

Reflections Inspired by Cowdry's General Cytology

The University of Chicago Press

Contents

INTRODUCTION

Karl S. Matlin, Jane Maienschein, and Manfred D. Laubichler

Cell biology as many scientists know it today is generally considered to have arisen after World War II and is often associated historically with particular technical developments, most prominently the electron microscope and cell fractionation. Despite its extraordinary success in describing both the structure and function of cells, modern cell biology tends to be overshadowed by molecular biology, a field of inquiry that developed in the same period. Nevertheless, cell biology, which considers both the molecular aspects of cells and cell form, is often more effective than approaches focused only on molecules in explaining biological phenomena at the cellular level.

The investigation of cells began, of course, much earlier than the postwar period. As a number of recent studies have explored, the cellular conception of life emerged gradually within a rich context of cultural trends, philosophical claims, changing epistemologies and aesthetic preferences, political debates, and institutional settings (Duchesneau 1987; Harris 1999; Parnes and Vedder 2008; Rheinberger and Müller-Wille 2007; Weigel 2005). Cells were identified in the seventeenth century, and during the eighteenth century and into the beginning of the nineteenth century, observations of mainly plant but also animal cells accumulated. By the beginning of the nineteenth century, improved light microscopes with significantly reduced chromatic aberration became widely available, and the pace of new discoveries about cells accelerated. Building on the work of Henri Dutrochet and François-Vincent Raspail in France, among others, Matthias Schleiden and Theodor Schwann produced widely read works in the 1830s suggesting that all organisms are composed of cells. Shortly thereafter, Robert Remak and Rudolf Virchow emphasized that all new cells are formed by division of old cells (Harris 1999).

As the nineteenth century progressed, cytologists increased our understanding of cell structures through morphological observations of embryos and other preparations, while also developing the protoplasm concept that began to address questions of cell chemistry (Geison 1969; see also Reynolds, chap. 3 in this volume). These observations also contributed to ideas about the theoretical foundation of biology as the fundamental science of life (Driesch 1893; Hartmann 1925 and 1933; Hertwig 1892; 1898; and 1906; Laubichler 2006; Schaxel 1919; Verworn 1895).

Further studies led to the formulation of hypotheses about the relative functions of the nucleus and cytoplasm, and the mechanism of cell division (Laubichler and Davidson 2008). Then, at the beginning of the twentieth century, cytologists correlated the distribution of Mendelian characters into dividing cells with the separation of chromosomes, and cytology became, for a time, closely linked with the study of heredity through the new field of genetics (see Allen, chap. 8 in this volume; and Sutton 1903). This link was grounded in a conceptual understanding of inheritance that predates the subsequent split into thinking in terms of genetics (transmission) and development (expression), a split triggered both by methodology and by new conceptual orientations (Laubichler 2014; Maienschein and Laubichler 2014). A casualty of this split into two experimental disciplines was the apparent loss of importance of cells to each.

Cytology, in the meantime, had become an increasingly experimental field based upon manipulations of early embryonic cells by Hans Driesch, Theodor Boveri, Wilhelm Roux, and others (Maienschein 1991). Although cytology still relied on the light microscope, biologists generally agreed that the processes within cells also depended on chemical reactions that researchers could not directly observe. There was, however, a dilemma. The living substance of the cell was the protoplasm, a gel-like mass that contained within it the nucleus and other "formed elements." Life was viewed as the consequence of protoplasmic organization, but the disruption of protoplasm believed to be necessary to study its chemistry was thought to render suspect the biological relevance of any reactions uncovered by these manipulations (Wilson 1896, 238; Geison 1969).

Cowdry's General Cytology

It is within this context that a group of American biologists decided to initiate a new project, the creation of a comprehensive cytology textbook with individual chapters from many of the leaders in the field, most of whom already interacted on a regular basis during summers at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts. When General Cytology was published in 1924, the volume sought to treat cytology comprehensively, but also to go beyond what the authors saw as the usual morphological considerations. Chapters focused on the chemical and physical activities of cells, and new techniques, such as cellular microsurgery and tissue culture, joined more traditional observational and experimental methods (Cowdry 1924). Edmund Beecher Wilson, one of the leading synthesizers of all knowledge of the cell up to then, noted in his introduction to the volume that General Cytology represented a new era of multi-perspectival cell biology.

The idea for General Cytology originated at a meeting of scientists working at the MBL in Woods Hole in September 1922. At the suggestion of Edward Conklin, the cytologist and anatomist Edmund V. Cowdry was asked to edit the volume. After accepting, Cowdry began assembling contributors, starting with the core group from the MBL (see Maienschein, chap. 2 in this volume). Among the individuals on this original list was Jacques Loeb, the great promoter of mechanistic views of the cell and formerly an MBL regular, with the suggested topic "Physical chemistry of the cell with special reference to proteins" (see fig. 1.1). Loeb later dropped off this list, presumably due to ill health (he died in 1924) (Pauly 1987). Robert Bensley, an anatomist from the University of Chicago and Cowdry's thesis advisor, was also proposed tentatively as author of two chapters on secretion and methods of fixation and staining. In the end, neither chapter by Bensley appeared in the final book, nor did a chapter by the botanist and physiologist Winthrop J. V. Osterhout on cellular permeability or a proposed "historical resume" by Fielding H. Garrison (see fig. 1.1). Other authors, however, eventually stepped in to fill these gaps.

A subsequent meeting determined the final title, list of authors, and suggestions for a publisher. The original working title was Cellular Physiology, indicating perhaps the desire to avoid what the group saw as the morphological connotations of the term cytology (fig. 1.1). By the time of the meeting, however, General Cytology was set as the final title. Wilson, who had been asked to write the introduction, planned to include historical material largely drawn from the upcoming edition of his book The Cell in Development and Inheritance, making a separate chapter on history superfluous (Wilson 1925). Merkel Jacobs, at the time responsible for directing the noted physiology course at the MBL, replaced Osterhout on cell permeability, and Thomas Hunt Morgan was added to write about the experimental analysis of the chromosome theory of heredity to pair with Clarence E. McClung's presumably more comprehensive chapter on the same topic (see fig. 1.2; see also Maienschein, chap. 2 in this volume, for more details).

While it seemed that Cowdry had preempted the others by speaking to Appleton Publishers about the book, in the end Frank Lillie, the MBL director and University of Chicago professor, approached the University of Chicago Press. On December 23, 1922, the contract for the book was completed (fig. 1.2). After that, adjustments to the content were minor but telling: Morgan changed his title to "Mendelian Heredity in Relation to Cytology," and Lillie added Ernest Everett Just as a coauthor. Just, an African American scientist and one of Lillie's former graduate students, was struggling to get recognition for his work, and Lillie may well have wanted to support him by giving him this opportunity while, at the same time, easing the burden of writing on himself (see fig. 2.1 in Maienschein, chap. 2 in this volume).

When published in 1924, General Cytology was very well received, and the book became somewhat of a best seller, especially considering that it ran to more than seven hundred pages and was intended for a specialized audience. As an edited volume put together by a collection of experts, the book was a concrete illustration that the scope of cytology had expanded beyond the capacity of an individual biologist, as Wilson noted in his introduction.

But was General Cytology, despite its popularity and stellar set of contributors, successful in transforming cytology into the modern, interdisciplinary science that the authors envisioned? That is less clear. It was forward-looking and did emphasize the importance of chemistry and even physics to understanding cellular phenomena. At the time, however, this was certainly not unique, since even earlier textbooks such as Allan MacFadyen's The Cell as a Unit of Life, published in Britain in 1908, as well as other works, also addressed the chemical aspects of cell function. In addition, by 1924 biochemists like Frederick Gowland Hopkins had already mounted an attack on the protoplasm concept, proposing to substitute enzyme specificity as the foundation on which the chemical organization of the cell was built (Needham 1949). Furthermore, Cowdry's book failed to predict the dramatic advances achieved just a short time later. In the 1930s Robert Bensley and, particularly, Albert Claude at the Rockefeller Institute began to disrupt current ideas about the cell and protoplasm, eventually leading to new epistemic strategies to explain cellular phenomena and to the merger of morphology, physics, and chemistry in cell studies (see Matlin, chap. 11 in this volume, and Bechtel 2006). Nevertheless, what General Cytology did accomplish was to mark the beginning of a transition in cell studies to an era in which the barriers constraining progress in cytology were overcome by new technologies and by collaborative and multi-perspectival approaches.

Reflecting on the Past, Present, and Future of Cell Biology

In October 2014 another group of leading scientists, historians, and philosophers of biology came together at the MBL in Woods Hole to reflect on the Cowdry volume from the perspective of the twenty-first century (table 1.1). Among the scientists were not only individuals who clearly identified as cell biologists, but also those more focused on gene expression and its regulation, topics many would consider more properly as molecular biology. The historians and philosophers were also an eclectic group. In presentations, several focused on events in cytology that preceded and produced the scientific context of the Cowdry volume, while others looked at what occurred afterward, and even explored future strategies to address cellular complexity.

On the basis of discussions at the meeting and at a subsequent workshop one year later, some of the original participants plus a few others who were not in attendance contributed chapters to this volume, Visions of Cell Biology. Although some contributors focused on Cowdry and his book, most used Cowdry's General Cytology and the imagined atmosphere of the MBL in 1924 as points of departure to try to understand not only how studying the cell has changed historically, but also how cell studies have affected and been affected by developments in the twentieth and even twenty-first centuries.

Our intention was neither to review the history of cell biology before and after Cowdry comprehensively, nor to attempt to directly relate the proposals articulated by the authors of General Cytology to later developments. Instead, Cowdry's book was used to inspire us to think about the study of cells from the microscopic observations of Schleiden and Schwann in the 1830s to the dynamic imaging of living cells today. In the end, we believe that our analysis establishes that cell biology is neither a discipline that arose in the modern, postwar period, nor one whose time has passed. Instead it is clear that the study of cells today exists within the mainstream of a historical continuum going back to the very origins of biology, a key part of the scientific study of life that was ushered in by the microscope and the ensuing recognition that, to paraphrase Wilson, everything alive began its existence as a single cell (Wilson 1925, 1).

Visions of Cell Biology is about how biologists attempted and continue to attempt to understand cells, not only before and after the appearance of Cowdry's General Cytology, but also in the present, when cellular complexity is beginning to yield to computationally based strategies. Technology is part of this story. Jutta Schickore (in chap. 4 of this volume) maps the use of the light microscope in the nineteenth and early twentieth centuries as it changed from a tool for simple observation to an experimental instrument. As microscopes improved, their magnification increased, and different forms of illumination and chemical dyes were added to the scientific repertoire to allow previously invisible structures to be seen. These manipulations created problems of interpretation, but also opened up possibilities to conduct real analysis of cells through the microscope. Karl Matlin (chap. 11 in this volume) picks up this thread by describing the introduction of electron microscopy as well as cell fractionation to cell biology in the 1940s and 1950s, while Rudolf Oldenbourg (chap. 12 in this volume) relates the reemergence of light microscopy in the modern period, exemplified by the work of the great microscopist Shinya Inoué and his application of sophisticated optics and digital imaging to living cells.

Another part of understanding cells is how the very idea of the cell has changed and continues to change. Andrew Reynolds (chap. 3 in this volume) traces emerging concepts of cellular organization, from the original use of the term cell that emphasized the cell wall and not the space within, to the focus by the end of the nineteenth century on the protoplasm, the critical living substance filling the cell's interior. As he makes clear, it was understood at the time that protoplasmic function was governed by chemistry. Yet even when General Cytology appeared, cytologists did not see a way to apply the emerging science of biochemistry to this problem, despite the pleadings of the great enzymologist Frederick Gowland Hopkins from Cambridge (Needham 1949). Instead, as Reynolds describes, they grasped mechanical and physical metaphors to try to conceptualize protoplasmic organization and find their way forward.

In her contribution, Jane Maienschein (chap. 2) looks most directly at the Cowdry volume itself and reviews the cell concept from that time and after, comparing views of the cell as an independent living unit and as a component responsible for the growth and differentiation of complex living systems. Against this background, she also details the creation of General Cytology in the 1920s, exploring the credentials of the biologists chosen as contributors, as well as the reception of the book after its publication and its impact on future conceptions of cells.

William Summers (chap. 5) adds to this by reminding us that the cell can be a source of a disease. He accomplishes this by following Edmund Cowdry's career both before and after General Cytology. During this time, Cowdry became an expert on intracellular pathogenesis and cellular inclusions caused by viruses and bacteria. As Summers points out, while Cowdry's histochemical approach was eventually superseded by molecular analysis and tissue culture, aspects of the classification schemes that he developed remain important. Lijing Jiang (chap. 6) follows another aspect of Cowdry's diverse career, the study of cell aging. Here the original belief that cells were immortal was replaced by the concept of a cellular lifespan called the Hayflick limit, eventually explained by telomere shortening.