Visions of Cell Biology: Reflections Inspired by Cowdry's "General Cytology"

VISIONS OF CELL BIOLOGY

CONVENING SCIENCE: DISCOVERY AT THE MARINE BIOLOGICAL LABORATORY

A Series Edited by Jane Maienschein

I am delighted to serve as editor for the new University of Chicago Press series Convening Science: Discovery at the Marine Biological Laboratory. These books will highlight the ongoing role the Marine Biological Laboratory plays in the creation and dissemination of science, in its broader historical context, as well as current practice and future potential. Each volume is anchored at the MBL and includes work about the MBL and its science and scientists; work by those scientists; work that begins with workshops, research, or courses at the MBL; collaborations made possible by the MBL; and so on. Books by, about, with, for, inspired by, and otherwise related to the MBL will capture the spirit of discovery by the community of MBL scientists and students. Some will be monographic, while others will be collaborative coherent collections.

We look forward to discovering new ideas and approaches that find their way into volumes of this series. I first did summer research, with a small NSF grant, as a graduate student in 1976; it led to my first edited volume inspired by this special place. Many other people have been similarly inspired, and this new series invites us to bring together our works into a collection of reflections on the MBL’s role in promoting discovery through its exceptional role in convening science at the seaside.

JANE MAIENSCHEIN

Series Editor

University Professor and Director of the Center for Biology and Society, Arizona State University

Fellow, Marine Biological Laboratory

VISIONS OF CELL BIOLOGY

REFLECTIONS INSPIRED BY COWDRY’S GENERAL CYTOLOGY

Edited by

KARL S. MATLIN, JANE MAIENSCHEIN, AND MANFRED D. LAUBICHLER

THE UNIVERSITY OF CHICAGO PRESS

Chicago and London

The University of Chicago Press, Chicago 60637

The University of Chicago Press, Ltd., London

© 2018 by The University of Chicago

All rights reserved. No part of this book may be used or reproduced in any manner whatsoever without written permission, except in the case of brief quotations in critical articles and reviews. For more information, contact the University of Chicago Press, 1427 E. 60th St., Chicago, IL 60637.

Published 2018

Printed in the United States of America

27 26 25 24 23 22 21 20 19 18    1 2 3 4 5

ISBN-13: 978-0-226-52048-3 (cloth)

ISBN-13: 978-0-226-52051-3 (paper)

ISBN-13: 978-0-226-52065-0 (e-book)

doi: 10.7208/chicago/9780226520650.001.0001

Library of Congress Cataloging-in-Publication Data

Names: Matlin, Karl S., editor. | Maienschein, Jane, editor. | Laubichler, Manfred Dietrich, editor. | Cowdry, E. V. (Edmund Vincent), 1888–1975. General cytology.

Title: Visions of cell biology : reflections inspired by Cowdry’s General cytology / edited by Karl S. Matlin, Jane Maienschein, and Manfred D. Laubichler.

Other titles: Convening science.

Description: Chicago ; London : The University of Chicago Press, 2018. | Series: Convening science

Identifiers: LCCN 2017026678 | ISBN 9780226520483 (cloth : alk. paper) | ISBN 9780226520513 (pbk. : alk. paper) | ISBN 9780226520650 (e-book)

Subjects: LCSH: Cytology. | Cells. | Cowdry, E. V. (Edmund Vincent), 1888–1975. General cytology.

Classification: LCC QH581.2.v58 2018 | DDC 571.6—dc23

LC record available at https://lccn.loc.gov/2017026678

This paper meets the requirements of ansi/niso z39.48-1992 (Permanence of Paper).

CONTENTS

1. Introduction

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

2. Changing Ideas about Cells as Complex Systems

Jane Maienschein

3. In Search of Cell Architecture: General Cytology and Early Twentieth-Century Conceptions of Cell Organization

Andrew Reynolds

4. Methodological Reflections in General Cytology in Historical Perspective

Jutta Schickore

5. Cellular Pathogenesis: Virus Inclusions and Histochemistry

William C. Summers

6. The Age of a Cell: Cell Aging in Cowdry’s Problems of Ageing and Beyond

Lijing Jiang

7. Visualizing the Cell: Pictorial Styles and Their Epistemic Goals in General Cytology

Beatrice Steinert and Kate MacCord

8. Thomas Hunt Morgan and the Role of Chromosomes in Heredity

Garland E. Allen

9. Epigenetics and Beyond

Jan Sapp

10. Heads and Tails: Molecular Imagination and the Lipid Bilayer, 1917–1941

Daniel Liu

11. Pictures and Parts: Representation of Form and the Epistemic Strategy of Cell Biology

Karl S. Matlin

12. Observing the Living Cell: Shinya Inoué and the Reemergence of Light Microscopy

Rudolf Oldenbourg

13. Enriching the Strategies for Creating Mechanistic Explanations in Biology

William Bechtel

14. Updating Cowdry’s Theories: The Role of Models in Contemporary Experimental and Computational Cell Biology

Fridolin Gross

Acknowledgments

List of Contributors

Index

Plates

CHAPTER 1

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.

Figure 1.1. An early proposal of contributors and topics for the volume that became General Cytology. Note the provisional title, Cellular Physiology. The handwritten notes may be those of Frank Lillie, since this document was found in his archives at the University of Chicago. Lillie submitted the proposal for the book on Edmund Cowdry’s behalf to the University of Chicago Press. From the Special Collections Research Center, University of Chicago Library, Frank Lillie Archives, box 2, folder 23.

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).

Figure 1.2. The first part of the formal agreement between the University of Chicago Press and Edmund Cowdry to publish General Cytology, dated December 23, 1922. Note the final list of contributors, including Thomas Hunt Morgan. As this document is from the press archives, handwritten notations are likely those of an editor. From the Special Collections Research Center, University of Chicago Library, University of Chicago Press Archives, box 126, folder 6.

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.

A different kind of perspective on cells is provided by Beatrice Steinert and Kate MacCord (chap. 7). They describe pictorial representation in General Cytology, suggesting that the forms that these representations take can reflect evolving epistemic strategies in the field of cytology itself. Realistic drawings of cells harken back to simple morphological descriptions designed to convey as accurately as possible what can be seen through the microscope. However, as they point out, additional drawings depict experimental manipulations of cells that point in directions beyond straightforward observation, consistent with the transcendent goals of General Cytology. Still others illustrate proposed explanations of biological phenomena or theories, abstractions that now have little to do with real representation of cells as physical entities but focus instead on ideas about cellular function derived from data that is not necessarily microscopic.

Bill Bechtel (chap. 13) explores the use of representations and images in the modern period by examining the roles of diagrams in mechanistic explanations of biological phenomena. He notes that diagrams are traditionally used to illustrate recomposed mechanisms, enabling the mental rehearsal of mechanistic steps, whereas the complex mechanisms recognized in current biology require different sorts of diagrams that are intuitively out of reach but can be deciphered through computational simulation and graph theoretic network analysis.

Another way that biologists try to understand cells is through genetics and the expression of genes. The discipline of genetics is rooted in the cytological study of chromosomes. After the rediscovery in 1900 of Mendel’s work on peas, Walter Sutton and Theodore Boveri linked chromosomes directly to Mendel’s characters (Laubichler and Davidson 2008; Sutton 1903). Boveri then developed a compelling conceptual framework that focused on the role of the hereditary material as a structured system of causal agents that controlled development and, by implication, evolution. This was the beginning of a trajectory that finds its most recent expression in the concept of gene regulatory networks, as Eric Davidson’s work and investigative pathway, which began more than six d ecades ago at the MBL, demonstrates so well (Laubichler and Davidson 2008).¹

After Boveri and Sutton, but well before any thought of gene regulatory networks, genetics took off through the study of model organisms, most prominently Drosophila melanogaster, and gradually separated itself from cytology. Nevertheless, in General Cytology, the importance of chromosomes and Mendelian genetics to cytologists led to inclusion of the chapters by McClung and Morgan. In Visions of Cell Biology, Garland Allen reviews Morgan’s contribution to explain why Morgan, at the late date of 1924, felt it necessary to focus on Mendelian genetics. He reports that, in fact, at that time aspects of what Allen calls the Mendelian-chromosome paradigm of heredity were still controversial, justifying Morgan’s vigorous defense, while also showing how the contributions from both Morgan and McClung led to the firm establishment of cytogenetics as a lasting part of cell biology.

Inheritance through genes on chromosomes is not, however, the only form of inheritance important to cell biology. Jan Sapp, in chapter 9, reminds us that nonchromosomal inheritance, or epigenetics, has been a constant theme in the history of cytology and remains of great significance today, despite narrowing definitions and continued confusion about the term epigenetics itself. Sapp explores the debates about cytoplasmic versus nuclear inheritance, along with inconsistencies in the logic suggesting that a one-dimensional code can give rise to a three-dimensional, spatially differentiated cell, by relating classical studies of Tracy Sonneborn on cortical inheritance in Paramecia. At the same time, he traces the path to our current definition of epigenetics as non-sequence-based changes in chromosomal DNA from proposals of Joshua Lederberg in the 1950s.

In the modern period, of course, the way we try to understand cells is through molecular mechanisms. Daniel Liu, in his contribution to Visions of Cell Biology, describes how chemists’ acquisition of the capacity to visualize molecules, specifically the heads and tails of lipids, enabled them to conceive of a model for the lipid bilayer (chap. 10). The lipid bilayer is the basis of the biological membrane enclosing cells and cellular compartments, and is perhaps the most iconic element of the cell’s three-dimensional form. As related by Karl Matlin in his chapter, one of the most significant next steps in chemically characterizing cells was to disrupt the cell membrane and separate the resulting membrane-bound compartments by centrifugation, the process of cell fractionation. This enabled determination of the biochemical identity of cellular organelles and, through parallel electron microscopy of the whole cell and its parts, also made functional inferences possible. Eventually, as he describes, this approach led to an almost comprehensive molecular understanding of certain biological processes within the cell.

The problem, though, is that the demands of trying to understand cells at the molecular level ultimately require a confrontation with cellular complexity. We now know many of the molecular parts of cells and their cellular locations because of high-throughput technologies, advanced microscopy, and bioinformatics. However, this knowledge has also demonstrated that the relationship between the molecular parts and cellular functions is decidedly nonlinear. As noted earlier, Bechtel describes an approach to this challenge by highlighting diagrams as they began to portray cellular processes only accessible through computational approaches, including the current focus on networks as a way of understanding biological mechanisms. Fridolin Gross (chap. 14) also describes the transition to computational modeling, certainly one of the most important developments in modern cell biology. He explores the different heuristics used by experimental versus computational cell biologists as seen from their analysis of cell cycle dynamics at finer and finer resolution. A take-home message from both Bechtel and Gross is that computational modeling of biological systems is an element of the epistemic strategy of cell biology that will continue to develop. Whether it will finally resolve debates about the relation of the parts (molecules) to the whole, which reaches back to the origins of biology itself, remains to be seen.

In the call for our workshops we emphasized a focus on the past, present, and future of cell biology as part of our reflections. While many of the scientists at the meetings gave detailed overviews of the present state in their various subdisciplines, and historians and philosophers provided detailed accounts in the form of specific case studies and thematic reflections, the future of cell biology remains somewhat unspecified. In light of Yogi Berra’s declaration (The future ain’t what it used to be.) this is not that surprising. Nevertheless, as with the Cowdry volume that initially inspired us to come together, Visions of Cell Biology demonstrates that historians, philosophers, and scientists bring different perspectives and approaches to their reflections. Cowdry and his group recognized in 1924 that such a confluence provides something more valuable than one contributor alone can offer. Perhaps, as Wilson noted about cell biology in 1924, it is no longer possible for any one scholar to write a history of cell biology. As a remedy, we offer Visions of Cell Biology, in which once again the MBL has brought people together to explore new directions.

Notes

1 Davidson gave a special lecture at the first workshop at the MBL that led to the development of this volume, and he and Manfred Laubichler intended to contribute a chapter. Unfortunately, Davidson’s untimely death prevented this from happening.

References

Bechtel, William. 2006. Discovering Cell Mechanisms. Cambridge: Cambridge University Press.

Cowdry, Edmund V., ed. 1924. General Cytology: A Textbook of Cellular Structure and Function for Students of Biology and Medicine. Chicago: University of Chicago Press.

Driesch, H. 1893. Die Biologie als selbstsständige Grundwissenschaft. Leipzig: Wilhelm Engelmann.

Duchesneau, F. 1987. Genese de La Theorie Cellulaire. Paris: Librarie Philosophique J. Vrin.

Geison, G. L. 1969. The Protoplasmic Theory of Life and the Vitalist-Mechanist Debate. Isis 60 (3): 272–92.

Harris, H. 1999. The Birth of the Cell. New Haven, CT: Yale University Press.

Hartmann, M. 1925. Aufgaben, Ziele und Wege der Allgemeinen Biologie. Klinische Wochenschrift 4:2229–34.

———. 1933. Allgemeine Biologie. Eine Einführung in die Lehre vom Leben. Jena: Gustav Fischer.

Hertwig, O. 1892. Die Zelle und die Gewebe. Grundzüge der Allgemeine Anatomie und Physiologie. Erster Theil. Jena: Gustav Fischer.

———. 1898. Die Zelle und die Gewebe. Grundzüge der Allgemeinen Anatomie und Physiologie. Zweiter Theil. Jena: Gustav Fischer.

———. 1906. Allgemeine Biologie. Jena: Gustav Fischer.

Laubichler, M. D. 2006. Biologie als selbstständige Grundwissenschaft und die allgemeinen Grundlagen des Lebens. In Der Hochsitz des Wissens; Das Allgemeine als wissenschaftlicher Wert, edited by M. Hagner and M. D. Laubichler, 185–205. Zürich: Diaphanes Verlag.

———. 2014. Gene Regulatory Networks. In Discoveries in Modern Science: Exploration, Invention, Technology, edited by J. Trefil, 393–401. Farmington Hills, MI: Macmillan.

———, and Eric H Davidson. 2008. Boveri’s Long Experiment: Sea Urchin Merogones and the Establishment of the Role of Nuclear Chromosomes in Development. Developmental Biology 314 (1): 1–11. doi: 10.1016/j.ydbio.2007.11.024.

Maienschein, J. 1991. Transforming Traditions in American Biology. Baltimore: Johns Hopkins University Press.

———, and M. D. Laubichler. 2014. Exploring Development and Evolution on the Tangled Bank. In Evolutionary Biology: Conceptual, Ethical, and Religious Issues, edited by P. Thompson and D. Walsh, 151–171. Cambridge: Cambridge University Press.

Needham, J., ed. 1949. Hopkins and Biochemistry 1861–1947. Cambridge: W. Heffer and Sons.

Parnes, O., and U. Vedder. 2008. Das Konzept der Generation: Eine Wissenschafts- und Kulturgeschichte. Berlin: Suhrkamp.

Pauly, P. J. 1987. Controlling Life. New York: Oxford University Press.

Rheinberger, H.-J., and S. Müller-Wille. 2007. Heredity Produced: At the Crossroads of Biology, Politics, and Culture, 1500–1870. Cambridge, MA: MIT Press.

Schaxel, J. 1919. Grundzüge der Theorienbildung in der Biologie. Jena: Gustav Fischer.

Sutton, W. S. 1903. The Chromosomes in Heredity. Biological Bulletin 4 (5): 231–50.

Verworn, M. 1895. Allgemeine Physiologie: ein Grundriss der Lehre vom Leben. Jena: Gustav Fischer.

Weigel, S. 2005. Genea-Logik: Generation, Tradition und Evolution zwischen Kultur- und Naturwissenschaften. Freiberg: Fink.

Wilson, E. B. 1896. The Cell in Development and Inheritance. New York: Macmillan.

———. 1925. The Cell in Development and Heredity. 3rd ed. New York: Macmillan. Orig. pub. as The Cell in Development and Inheritance in 1896; 2nd ed., 1900.

CHAPTER 2

CHANGING IDEAS ABOUT CELLS AS COMPLEX SYSTEMS

Jane Maienschein

As Edmund Beecher Wilson finished writing the third and final edition of his The Cell in Development and Heredity, he noted that in the future probably no single author could write such a cell biology text. The subject had become too complex and required too many different kinds of expertise to do it justice. About the same time, Wilson joined Edmund Cowdry and other leading biologists in a workshop at the Marine Biological Laboratory (MBL), where the distinguished group divided up the topics to write the collective 1924 volume General Cytology (Wilson 1925; Cowdry 1924). Cowdry then convened a larger and even more diverse group to produce two volumes on Special Cytology (Cowdry 1928; Cowdry 1932).

Far from being of merely antiquarian interest, these volumes reveal underlying assumptions that both reflected and informed the directions of scientific research. The 1924 Cowdry volume focused on the architecture and activities of individual cells, not primarily as building blocks of living organisms but also as the fundamental units that were themselves living, and the authors emphasized the value of studying these living cells in detail. The group clearly saw the beginning of a new field of cell biology emerging, one that might lose the coherence of a single approach but gain from different points of view, using different techniques to ask different questions about complex cells and their activities.

This chapter looks at the context in which Cowdry’s volume appeared, a context constructed on the foundation of the first cell theory of 1839 and subsequent developments. The story leads to questions about what the Cowdry volume tells us about the science of understanding cells more generally. It looks at what the 1924 volume offers in seeing cells as having gained autonomy, integrity, and biological importance as complex living systems in their own right. In addition, some of the chapters and reviews focus on understanding that the individual cells work together to make up complex organisms, such that organization arises through their connections. Yet the chapters mostly remain focused on the individual cells themselves rather than on how they communicate with each other and work as a whole. The Cowdry volume presents an American story, focused on Woods Hole at a time after World War I when scientists in the United States aspired to scientific leadership. To gain perspective on the contributions of Cowdry’s volume, it is useful to start briefly at a prominent discussion at the centennial of the cell theory for a broader view looking back, and then to move on to General Cytology itself.

Reflecting on the First Century of Cell Theory

In his introduction to the centennial volume entitled The Cell and Protoplasm in 1940, editor Forest Ray Moulton noted that the American Association for the Advancement of Science was publishing the book as part of a series. It grew out of a symposium, held in 1939, to celebrate the centennial of Matthias Schleiden and Theodor Schwann’s introduction of the scientific cell theory. Because of the rich history of thinking about cells up to that time, Moulton felt that in a sense the Cell Theory is not new. Yet, he continued, In another sense the Cell Theory is always new, for every discovery respecting this primary and essential unit of living organisms, both plant and animal, has raised more questions than it has answered and has always widened the fields of inquiry (Moulton 1940, Foreword). The volume set out to show both what was old and well established and what was new a century after the original idea of cells.

By 1940, discussion of cells usually separated plant, microbial, and animal cells. For plants, discussion typically involved looking at such predictable topics as cell walls, while discussion of animal cells looked more closely at delineation of individual cells; contents of cells, including nucleus, cytoplasm, and organelles; and environments, both internal and external to each cell. Along the way came considerations of biochemistry and cell physiology. More surprising in the 1940 volume are the less standard chapters on microbiology, viruses, enzymes, hormones, and vitamins. The choice of topics and of contributors makes clear just how much remained in 1940 to be discovered about cells and especially about the ways they interact with each other as well as with their environment. The contributors realized that they still knew relatively little about how the individual cells add up to an organized, whole, complex organism, though they recognized that the process of making coordinated combinations of parts was key to understanding living systems and organisms.

We see this emphasis on individual cells in textbooks of the time as well. For example, Lester W. Sharp’s very widely used Fundamentals of Cytology of 1943 (as well as other editions) laid out the way that cytoplasm and nucleus work in the cell, looked at different kinds of cells, and recognized that cells make up organisms, but had relatively little to say about the latter point. Sharp noted that in addition to the cell theory focused on the cells themselves, other researchers had a different view of living organisms that supported an emphasis on each organism as a whole. The two different perspectives have to come together in some way, Sharp recognized, for in every normal mass of protoplasm, whatever its growth pattern or degree of differentiation, the many diversified activities are so coordinated that it behaves as a consistent whole, or individual, from the beginning of development onward; without such harmony there obviously could be no organism (Sharp 1943, 20). Yes, but how could this harmony be achieved?

The connections were not yet clear. Some biologists continued to look at organisms as organized living systems that happen to consist of cells, while others looked at aggregations of cells as making up organized living systems. At issue was partly a matter of emphasis, but also partly a matter of causal efficacy. Do cell divisions and actions cause organisms, or does some integrated wholeness cause cells to behave as they do? What drives the integration of the whole organism? These were still questions in the 1940s, and the discussion shows that biology had not embraced a single cell theory to explain the basis for all living systems.

Sharp explained that cell structure and function affect or perhaps even effect the organism, but it remained unclear just how that happens. In an earlier picture of cells as structural units or building blocks, it was easier to treat them like bricks or stones that combined into a larger organism through forces outside the cells themselves. But if cells were each living units in their own right, then how do all those separate cells relate to the organism as a whole, and how do they make up that whole? How could new research resolve persistent debates? In particular, by the end of the nineteenth century, in the face of increasing knowledge about protoplasm and internal workings of cells, which theory about life should hold? The proponents of the cell theory stressed the cell as the primary agent of organization, while adherents of the organismal theory insist upon the primacy of the whole, cells when present being important but subsidiary parts (Sharp 1943, 21). Furthermore, looking at evolutionary relationships by comparing studies of different organisms suggested that a different kind of protoplasm might serve to connect cells and might thereby help to bring together coordinated whole organisms in somewhat different ways and not necessarily in exactly the same processes and patterns for each kind of organism. Many questions remained in 1940, including questions about what cell theory was and how it had changed over time.

Again, this work of the mid–twentieth century reinforced just how much had been learned about the details of cells, and yet how little that knowledge revealed about the ways cells work together in a coordinated way in more complex animals. It is worth looking at how the science had gotten to this point. The history of cell biology shows a first stage of thinking about cells as the structural units of living organisms, followed by a stage of thinking about cells as themselves more nearly the agent[s] of organization, as Sharp put it. Reflecting on the development of cell theory took Sharp, Cowdry’s group, and takes us as well, to previous studies of cells, starting with Schleiden and Schwann.

In the Beginning

Most of us have heard something about the basic story of Schleiden and Schwann and the cell theory that they invented, which is recounted in textbook after textbook—except that we do not know the historically accurate story, because the textbooks usually get it wrong, or partly wrong. Those accounts tell of these two German innovators, one working on plants and the other working on animals, as coming up with the theory that cells are the fundamental units of life. The story goes that these two began to put together the available evidence and reasoning to develop what they called the Zellenlehre and what others labeled the Zellentheorie that has grounded all of biology since (Schwann 1839).

Everybody likes a good myth, and like most, this one is not completely inaccurate. Matthias Schleiden and Theodor Schwann