Membranes to Molecular Machines Active Matter and the Remaking of Life
by Mathias Grote
University of Chicago Press, 2019
Cloth: 978-0-226-62515-7 | Electronic: 978-0-226-62529-4
DOI: 10.7208/chicago/9780226625294.001.0001
ABOUT THIS BOOKAUTHOR BIOGRAPHYREVIEWSTABLE OF CONTENTS

ABOUT THIS BOOK

Today's science tells us that our bodies are filled with molecular machinery that orchestrates all sorts of life processes. When we think, microscopic "channels" open and close in our brain cell membranes; when we run, tiny "motors" spin in our muscle cell membranes; and when we see, light operates "molecular switches" in our eyes and nerves. A molecular-mechanical vision of life has become commonplace in both the halls of philosophy and the offices of drug companies, where researchers are developing “proton pump inhibitors” or medicines similar to Prozac.
 
Membranes to Molecular Machines explores just how late twentieth-century science came to think of our cells and bodies this way. This story is told through the lens of membrane research, an unwritten history at the crossroads of molecular biology, biochemistry, physiology, and the neurosciences, that directly feeds into today's synthetic biology as well as nano- and biotechnology. Mathias Grote shows how these sciences not only have made us think differently about life, they have, by reworking what membranes and proteins represent in laboratories, allowed us to manipulate life as "active matter" in new ways. Covering the science of biological membranes in the United States and Europe from the mid-1960s to the 1990s, this book connects that history to contemporary work with optogenetics, a method for stimulating individual neurons using light, and will enlighten and provoke anyone interested in the intersection of chemical research and the life sciences—from practitioner to historian to philosopher.

The research described in the book and its central actor, Dieter Oesterhelt, were honored with the 2021 Albert Lasker Basic Medical Research Award for his contribution to the development of optogenetics. 

AUTHOR BIOGRAPHY

Mathias Grote is assistant professor at Humboldt-University Berlin, Germany.

REVIEWS

"Membranes to Molecular Machines is a masterful study of the hidden origins in chemical practice and an explanation of much of today's molecular biology. As Mathias Grote sheds light on how scientists unraveled molecular mechanisms related to energy, metabolism, and cognition, he expands the scope of our historical understanding and crucially enriches our theoretical armory. In giving scientists' investigations of active biomolecules center stage, and in arguing for a materialism based on chemical concepts and practices, Grote draws the lines of the historiography of the modern life sciences anew."
— Carsten Reinhardt, Bielefeld University

"In the 1950s and 1960s, the determination of the structure of DNA and the decipherment of the genetic code were revolutionary events in biology that have been often and well described. It is not the case for the process of molecularization of biology, which was initiated in the 1970s and transformed the whole discipline. In this book, Mathias Grote describes a lesser-known—but probably one of the most significant—episodes of this molecularization: the conversion of the monotonous structure of cellular membranes into an organized ensemble of superb macromolecular machines. It was a leap in our understanding of the functions of cellular membranes, and one that opened a door to new therapeutic approaches to numerous diseases."
— Michel Morange, Centre Cavaillès, Ecole Normale Supérieure

"How have we come to understand life and our own bodies in terms of molecular machines? This question drives Mathias Grote's fascinating inquiry. Focusing on cell membranes, channels, and pumps as paradigmatic objects of analysis and synthesis, Grote forcefully argues that there has always been more than genes to the molecular study of life. This book is a major new contribution to both the history and philosophy of recent biology and our understanding of a molecular vision of life."
— Soraya de Chadarevian, University of California, Los Angeles

"According to the dominant narrative in the history of biology, the most important developments in the last half of the twentieth century centered on DNA and genetics. In Membranes to Molecular Machines, Mathias Grote argues that this history omits other areas of the life sciences not illuminated by the spotlight of the DNA saga. One such area is what Grote calls the 'materialization' of membrane machines. Using the fascinating story of bacteriorhodopsin as a case study, he follows the discovery of the protein through its structural determination by electron microscopy to the description of its function as a light-stimulated proton pump. Along the way, he reviews the development of the biological membrane concept from early models to reconstitution studies, and impressively exploits interviews and the personal archives of leading investigators to construct his account. In this way, he produces a fuller and more accurate view of the history of biology in the twentieth century."
— Karl Matlin, University of Chicago and the Marine Biological Laboratory

"[Grote] gives structural biology time in the limelight—a break from the genetics and genomics frenzy of the modern era—and traces the history behind how the view of membranes evolved as electronic technologies gained traction among scientists. Packed with history and sprinkled with philosophical commentary, an occasional pun or two, and a smattering of German words, Membranes to Molecular Machines makes for a good read, informative and thought-pro­voking."
— Small Things Considered

"This book opens a new chapter in the history of the life sciences of the second half of the twentieth century. To this day, much of the historiography remained centered on molecular genetics with its heroes. Mathias Grote presents a different, immensely illuminating focus. Revolving around the concepts of 'active matter' and 'molecular machinery,' this book cannot only be read as an archaeology of nanobiology, but it is also a historically rich contribution to current debates around 'new materialism.'"
 
— Hans-Jörg Rheinberger, director emeritus at the Max Planck Institute for the History of Science

“A deeply researched and well-supported history describing the synthesis of our modern understanding of biological membranes.”
— Choice, 2020 Outstanding Academic Title

"[A] highly original study . . . . Richly documented. . . . Life, his book persuasively shows, is not only transmission; it is also a way of being in the world and interacting with it."
— Isis: A Journal of the History of Science Society

"Grote blends insights and interests across the history, philosophy, and social study of twentieth century biology, with the additional explicit intention that these can also inform understanding of biological science in the present. . . . While in general this approach might sound very familiar to historians and philosophers of science, the specific way in which Grote achieves this study is quite novel. Rather than looking for a particular question, technique, or puzzle which organised research in his communities of interest, c. 1970s-1990s, he instead pursues a ‘genealogy of practices'."
— NTM Zeitschrift für Geschichte der Wissenschaften, Technik und Medizin

"In his book, Mathias Grote has covered a wide range of topics and philosophical aspects from the beginnings of membrane biology to the development of biochips. It is not only suitable for students and prospective scientists, but also offers teaching faculty an exemplary source of information about the beginnings of a small field of research that later led to new unforeseen methodological and conceptual developments."
— Biospektrum

"[Grote's] study not only illuminates a much broader field but also permits an analysis of the rise of the molecular life sciences as we know them today, with its orientation to molecular machinery. . . . This is a very readable book which explores how our understanding of the composition, structure, and function of membranes has evolved during the last century. The author successfully draws on his proximity to the field and his professional relationships with several of its key scientists to provide a rich history of the how the field advanced and to offer insights into the personalities and motivations of the major figures in the field."
— FASEB Journal

"As an experimental researcher, I found Grote’s writing captivating and informative, with concise explanations of complex science, accompanied by pictures of the researchers along with images from their laboratory notebooks that tie in with the stories. Grote’s book makes for an intense read and will be of most interest to biological researchers, as well as to historians and philosophers of the life sciences."
— Shivangi Pandey, History and Philosophy of the Life Sciences

TABLE OF CONTENTS


DOI: 10.7208/chicago/9780226625294.003.0001
[cell;colloidal chemistry;cybernetics;Davson-Danielli model;receptor;signal transduction;surface;structural biology;enzyme;molecular biology]
This chapter introduces basic concepts and experimental approaches of biological membrane and protein research, and briefly reviews their development from the interwar period until the 1960s, sketching connections to problems, methods, and concepts from neuro- and electrophysiology, bioenergetics, and enzymology, as well as cell and structural biology. The bottom line of this chapter is that since an earlier heyday of research in the context of interwar colloidal chemistry and cell biology, membranes have remained at one remove from providing molecular mechanisms, with phenomena such as the electrical excitation of nerves not being explained on a microphysical level. In the 1960s, membranes were couched between the hope (uttered by Max Delbrück, for example) of finding new cybernetically inspired principles of life following up on the successes of molecular biology, that might explain cellular signal transduction or energy generation on the one hand, and on the other the experimental difficulties involved in getting a hold on membranes. The history of Hodgkin and Huxley’s studies on neuronal action potentials illustrates this as much as models of the cell membrane by electron microscopy or studies of cell permeability by Hugh Davson, James F. Danielli, and others.
This chapter is available at:
    https://academic.oup.com/chica...


DOI: 10.7208/chicago/9780226625294.003.0002
[cryo-electron microscopy;bioenergetics;Richard Henderson;laboratory notebooks;Dieter Oesterhelt;Max Planck Institute of Biochemistry;Laboratory of Molecular Biology Cambridge;rhodopsin;pump;1970s]
This chapter comprises a detailed case history on the emergence of what was to become a model of a molecular “pump,” the photoactive protein bacteriorhodopsin. The surge of research on this brand-new research object is part of the early 1970s’ “membrane moment,” which rapidly transformed the field. The unfolding of research at the University of San Francisco, the Max Planck Institute of Biochemistry, and Cambridge’s Laboratory of Molecular Biology shows a coalescence of concepts and methods from enzymology, organic chemistry, physiology, and structural biology around the concrete materialization of a membrane and its active protein. Thereby, this chapter provides a history of active matter avant la lettre, highlighting the field’s manifold connections to chemistry. Laboratory notebooks reveal transformative steps and the impact of materiality on this research project from an analysis of membrane structures to the study of an exemplary molecular machine. This chapter provides insight into the work style and topics of a novel, influential generation of molecular biologists, which changed the scope of these sciences, and it can be read as an element in a prehistory of optogenetics, a current approach that makes use of such molecular machinery to modify neuronal activity.
This chapter is available at:
    https://academic.oup.com/chica...


DOI: 10.7208/chicago/9780226625294.003.0003
[chemiosmosis;liposome;Peter Mitchell;Har Gobind Khorana;Efraim Racker;recombinant DNA;synthetic biology;peptide synthesizer;synthetic gene;molecular mechanism]
This chapter analyzes practices of (re-)making biological molecule and cell models, throughout the 1970s and 1980s, thereby conceiving of a genealogy of syntheses between chemistry and the life sciences. The production and use of liposomes (membrane-ensheathed vesicles) as models of cell membranes was pioneered by biochemist Alec D. Bangham and transferred into bioenergetics by Efraim Racker around 1970. Later, methods of recombinant DNA and also organic chemical synthesis added to these modes of modifying life’s material inventory. Har Gobind Khorana, a chemically-minded molecular biologist inspired by syntheses, set out to gradually remake life’s components, producing the first functional synthetic gene, before transferring this making approach to membranes and proteins. Khorana’s research illustrates how mechanisms have been spelled out by taking apart, modifying, and remaking life’s components in what is called a “plug-and-play” mode of research. This chapter’s focus on practices of making biological molecules and structures outlines a genealogy of recent synthetic biology, changing perspectives from research programs or conceptual innovation into a slow and piecemeal change through technique (as was also the case for the automated synthesis of DNA and proteins, as devised by Rockefeller chemist Bruce Merrifield).
This chapter is available at:
    https://academic.oup.com/chica...


DOI: 10.7208/chicago/9780226625294.003.0004
[biochip;bionics;biotechnology;chemical industry;computing;Germany;journal;molecular electronics;nanotechnology;optogenetics]
This chapter tells the story of attempts to turn biomolecules into technologies that were to lead to improved, life-like computing. The history of biochips adds an unexpected dimension to the history of both bio- and nanotechnologies. Far from venture capital and biomedicine, 1980s biotech and recombinant DNA appear here as radical attempts to redesign existing technology through inspiration from life. Such efforts were endorsed by, for example, cell biologist Lynn Margulis and nanotech posterchild Eric Drexler. Projects aiming to tackle life’s molecular machinery for computing existed in US labs and start-ups as well as within the German chemical industry. By analyzing the failed attempt to materialize a biochip, this chapter puts more flesh on the bones of nanotech history, and reveals its interconnections to materials and the life sciences. Moreover, this chapter describes changes in scientists’ discourse on novel technologies in various media of the 1980s, as it follows molecular machinery from the scientific press into novel magazines or newspapers. Finally, 1980s biochips research will be juxtaposed to optogenetics, a recent endeavor to make molecular machinery work within organisms in order to modify their behavior or to create semi-organic prostheses.
This chapter is available at:
    https://academic.oup.com/chica...


DOI: 10.7208/chicago/9780226625294.003.0005
[active matter;chemistry;materiality;molecular dynamics;historiography;life sciences;scientific persona;entrepreneur;molecular dynamics;San Francisco]
This chapter reflects on materiality and specifically active biological matter as a novel historiographical nucleus to conceive of the recent history of the life and chemical sciences, as it reflects on the philosophical question about the ontological status of molecular machinery in light of this book’s history. Furthermore, the history of membrane and protein research is positioned within the historiography of the twentieth-century life sciences, making a case to move away from genetics as shaping the dominant narrative, and highlighting the continuous relevance of physiological and chemical research to these sciences’ present states. A number of questions for further research that this book has opened up will be sketched, such as on the temporality and geography of recent sciences. Not least, the chapter discusses the question of how to characterize the persona of 1970s and 1980s life scientists in between academia, entrepreneurship, mainstream science, and application.
This chapter is available at:
    https://academic.oup.com/chica...