Making Mice: Standardizing Animals for American Biomedical Research, 1900-1955 available in Hardcover, eBook
Making Mice: Standardizing Animals for American Biomedical Research, 1900-1955
- ISBN-10:
- 0691016364
- ISBN-13:
- 9780691016368
- Pub. Date:
- 03/21/2004
- Publisher:
- Princeton University Press
- ISBN-10:
- 0691016364
- ISBN-13:
- 9780691016368
- Pub. Date:
- 03/21/2004
- Publisher:
- Princeton University Press
Making Mice: Standardizing Animals for American Biomedical Research, 1900-1955
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Overview
Karen Rader introduces us to mouse "fanciers" who bred mice for different characteristics, to scientific entrepreneurs like geneticist C. C. Little, and to the emerging structures of modern biomedical research centered around the National Institutes of Health. Throughout Making Mice, Rader explains how the story of mouse research illuminates our understanding of key issues in the history of science such as the role of model organisms in furthering scientific thought. Ultimately, genetically standardized mice became icons of standardization in biomedicine by successfully negotiating the tension between the natural and the man-made in experimental practice.
This book will become a landmark work for its understanding of the cultural and institutional origins of modern biomedical research. It will appeal not only to historians of science but also to biologists and medical researchers.
Product Details
| ISBN-13: | 9780691016368 |
|---|---|
| Publisher: | Princeton University Press |
| Publication date: | 03/21/2004 |
| Edition description: | New Edition |
| Pages: | 312 |
| Product dimensions: | 6.00(w) x 9.25(h) x (d) |
About the Author
Read an Excerpt
Making Mice
Standardizing Animals for American Biomedical Research, 1900-1955By Karen Rader
Princeton University Press
Copyright © 2004 Princeton University PressAll right reserved.
ISBN: 978-0-691-01636-8
Introduction
WHY MICE?
On October 23, 1947, fourteen people and tens of thousands of laboratory mice perished when the sleepy resort community of Bar Harbor, Maine, burned to the ground. A forty-mile wind-borne fire front triggered early evacuation of most of the town's estimated 4,300 human residents. Some escaped by car or bus, and thousands more rushed to the docks to await rescue; the scene, a Coast Guard official told the New York Times, "was reminiscent of Dunkirk." Many loyal caretakers of the island's nearly three hundred palatial estates stayed behind to fight the flames "with nothing but brooms." Elizabeth Russell, a scientist at the Jackson Laboratory, Bar Harbor's nearly twenty-year-old institution for research in mammalian genetics and cancer, remembered seeing a small plume of smoke on October 14, while at a staff meeting at nearby Hamilton Station, and marveled at how the "tiny fire had continued to grow." She and the rest of the staff quickly escaped the premises and were spared injury, but their experimental organisms fared less well. The fire completely destroyed the original lab building, and two new "mouse houses"-the second of which was under construction at thetime-were seriously damaged. Except for the few hundred mice readied for shipment to researchers in a corner isolation room, all ninety thousand resident rodents (housed primarily in wooden mouse boxes) died in the blaze. When the embers cooled, those who first arrived on the scene remember two things: the strange and unforgettable smell of burnt mice, and the comment that the lab's founder, geneticist Clarence Cook Little, made upon surveying the damage: "Now we can see the water" (fig I.1-I.4).
The next day, as Maine's governor scrambled for federal disaster relief money to rebuild America's "Vacationland," Little received multiple unsolicited offers of aid to re-establish the "JAX" mice (as they had come to be known, from an abbreviation of the lab's cable address). The Rockefeller Institute for Medical Research and the Carnegie Institute both pledged facilities for maintaining the surviving mice, and before they knew the full extent of the damages, the boards of the American Cancer Society and the National Institute of Health (NIH) held special meetings where they decided to offer Little a replacement building for the continued production of mice in Bar Harbor. But perhaps most remarkably, individual geneticists and medical researchers who had previously received stocks of JAX mice began sending back breeding pairs of those same stocks to Bar Harbor. Little told the Rockefeller Foundation's Warren Weaver that there was "hardly a genetics or cancer research institute east of the Mississippi" that didn't respond to his lab's crisis. He analogized the animals' return to a biblical miracle: "The bread which we cast upon the waters several years ago, is now returning to us." By contrast, Little claims to have received only one angry letter from a local "anti-vivisectionist women's club," which expressed regret "that Dr. Little and his fellow scientists had not been burned up in the blaze instead of the mice."4 By 1949, national fundraising drives combined with additional governmental support to ensure that Jackson Laboratory would rise from its ashes. That year in a foundation endorsement letter, the lab's Board of Trustees noted that the institution had been completely rebuilt and had reclaimed its status as the "Bureau of Biological and Medical Standards." During the fall of 1953, Little felt so confident about the lab's future that he contacted his lawyer about his ultimate wish: to link the success of the JAX mouse to another popular mouse who had also weathered the Depression era. He wrote:
I was very much interested in the article in Life on the Anniversary of the Jackson Laboratory, that in a somewhat similar, but less sensational, way has done for the mouse in science what Disney has done for it in amusement. The possibility of arousing Disney's interest in doing something of a philanthropic nature along the line of a factual, or partly factual film, to tell the story of the mouse (which might easily be a brother or other relative of Mickey) has been in [our] minds ... for some years.
Little did eventually correspond with Disney, but apparently nothing ever came of his idea. He later told a friend the moral he drew from this interaction, as well as from public responses to the 1947 fire: "In these days, when support of basic research by the American public is its chief and constantly growing hope, efforts of this kind, which might seem through Victorian eyes to be undignified, are not really as shallow and superficial as they may seem."
More than fifty years later, the "Great Bar Harbor fire" represents a relatively minor event in American history, and yet it raises many compelling questions for historians of science and culture. Why were such a large number of mice gathered in a little-known, nonprofit cancer research laboratory in Maine, and why did their animal deaths warrant national media attention alongside the direct effects of the fire on the human inhabitants of Mount Desert Island? Why did the NIH, as well as so many researchers and foundations, desperately want to reassemble JAX Lab and its mouse colony, and why did so few persons concerned with animal welfare or animal rights object to this project? Why was there more national financial support available for quickly rebuilding JAX's mouse houses than there was for rebuilding Bar Harbor's own natural resources (and thereby its local tourism industry)? And finally, why might Little have thought Mickey Mouse would prove a powerful tool for doing so-even while Walt Disney himself found this idea problematic?
This book seeks to answer these questions by examining the contingent process through which American biological and medical researchers developed the mouse into a standardized laboratory organism during the period from 1900 to 1955. Like the science it reconstructs, this book is based in large part on scientists' own accounts of their work-research articles, correspondence, and other bureaucratic paper trails of their administrative interactions-but it also mines the historical record for traces of this same science's more public culture: congressional testimony, publicity films, popular magazine feature writing, and so forth. By crafting a conversation between these rich bodies of primary and archival source material, it strives to explore the nature of laboratory mouse standardization from the perspectives of the animal's developers as well as its various users: mouse genetics experimenters in labs at JAX, medical researchers who paid to have JAX mice sent to their own labs, science policymakers who located a program for coordinating bench-top research in murine bodies, and the American public, who at once consumed laboratory mice as cultural icons of biological research and supported mouse experiments and production with their tax dollars. I situate my account at the locus of mass production that historians of technology have deemed "the consumption junction," but the engine driving my account is a concern for the complex interplay between science and society, so "users" is a theoretical category I employ very idiosyncratically. Taking cues, respectively, from the work of historians T. J. Jackson Lears and Phillip Pauly, I define "consumption" as a process of "individual choice and consciousness, wants and desires ... in the context of social relations, structures, institutions, systems"-mainly because I am interested in perpetuating a definition of culture that emphasizes its historical and etymological roots at "the intersection of the biological and the technological" in America (especially during the early decades of the twentieth century). Ultimately, then, this book describes the means by which scientists developed JAX mice into standard mammalian research organisms not just through the eyes of researchers doing experiments in laboratories, but through their encounters with the politicians and policymakers of the fledgling national system of biomedical research emerging in this period. At the same time, by considering how inbred mice became iconic symbols of the value of standardization within our culture's changing understandings of animals and science in the twentieth century, I am also suggesting that the public audience for this work must be considered another kind of scientific user. To understand how broader cultural imperatives shaped the practical nature of standardization in research, and vice versa, is to understand the social and scientific meaning of biology in twentieth-century American life.
Focusing primarily on the inbred mice produced by one institution-the Jackson Lab-my story chronicles both the specific evolution of one animal species (mus musculus, the common mouse) through its journey into the laboratory, as well as a key period of disciplinary and methodological reorganization in biology. Inbred strains were first developed and promoted for philanthropically funded cancer genetics research at the Jackson Lab, but financial deficits brought about by the Depression provoked director C. C. Little to circulate these animals more widely, as "pure" biological reagents for more diverse lines of medical research. After World War II, as the genetic etiology of cancer began to wane in experimental cancer work, the social and scientific need for good mammalian models of radiation damage gave the inbred mouse a new mission. Along with these changes in scientific agenda, however, came shifts in the patronage of science and the commercialization of its infrastructure (now including standardized lab animals). These developments nearly rendered the coexistence of research and mouse production at Jackson Lab unsustainable.
In the early years, JAX scientists constantly fought back the tide of what they came to know as "operation bootstrap"-the piggy-backing of mouse research onto the development of the production colony-but in retrospect, their persistence paid off. In the 1950s, although JAX was widely acknowledged as (in the words of one trustee) "the bureau of mouse standards," C. C. Little could barely convince either medical genetics researchers or granting agencies that mammalian genetics was worth much investment. Today sales of JAX inbred mice to outside researchers exceed two million organisms annually. Furthermore, since its inception in 1959, JAX's frozen mouse embryo repository has accumulated more than 2,400 strains of mouse mutants. These animals, instead of being bred, are stored more cost effectively as embryos in vats of liquid nitrogen. Kenneth Paigen, Jackson Lab director from 1989 to 2000, claims that "more than 95 percent of all mouse models used in the world come from the Jackson Laboratory." As the 2001 JAX Annual Report concluded: "Researchers around the world agree that JAX Mice are the 'gold standard' of genetic purity in mouse models," citing a 2000 report from Michael Festing and Elizabeth Fisher that "at least seventeen Nobel prizes ... have flowed from the Jackson Laboratory." One of these Nobel Prizes was awarded in 1980 to a JAX researcher, George Snell. Snell's congenic strains, which he began developing in the 1940s and completed in 1957, enabled him to identify and characterize the key genetic locus of histo-compatibility in mice. This work (along with that of Baruj Benacerraf and Jean Dausset on the analogous phenomenon in human tissue transplant) was honored by the Nobel Committee as "laying the foundation for our knowledge of 'self' from 'non-self.'"
The Jackson Lab's research successes since the 1950s have not been limited to Snell's work. In the late 1950s and 1960s, for example, staff scientist Leroy Stevens was doing tumor transplantation work on Strain 129 mice, and he made a leap that would "profoundly affect stem cell technology a decade later." When Stevens noticed that the primordial germ cells that gave rise to teratomas looked a lot like the cells of considerably earlier embryos, he decided to transplant cells from various stages of early Strain 129 mouse embryos, including inner cell mass cells, into testes of adult mice. Some of these early embryo cells gave rise to teratomas, which, when transplanted into mouse bellies, displayed the ability to generate an impressive range of tissue types. Stevens called these cells that could support differentiation "pluripotent embryonic stem cells"-the origin of the term "stem cells."
By far, however, one of JAX's proudest accomplishments is that the National Cancer Institute has renewed the lab's designation as a "Cancer Center" for genetic research every five years since it initially bestowed on JAX this honor in 1983. "That designation," Paigen wrote in his 2001 Annual Report Director's Message, "is vital to the Jackson Laboratory because basic cancer research is a thread woven into the fabric of our very institution." For the twenty-five years between 1955 and 1980, that thread was not always acknowledged by science policy-making bodies, but it is one of the arguments of this book that it was there all along, ready to be rewoven (by new techniques of mammalian genetic manipulation) into the tapestry that is modern biomedical research. In fact, this book's pre-1955 focus highlights how problems of genetics once considered unanswerable in mammals were later transformed into cutting-edge research fields. Thus the Rockefeller Foundation program officer who in 1951 wrote that "the most valuable export of the Jackson Memorial Laboratory is in terms of boxes of mice rather than scientific publications" failed to appreciate the important, but often unpredictable, connections between the two. Mus musculus and its many mutants were well poised to colonize the laboratories of the new organismal molecular biologists of the 1970s, and work with mice has ranked especially significant in recent cancer research, as well as in the emergence of other biomedical fields such as molecular immunology and genetic epidemiology.
Ironically, even mammalian genetics-the field scientists and policymakers labeled too slow and laborious to invest in during the early twentieth century-has undergone what can only be described as an explosion in the last decade. The first mammalian gene ever cloned and sequenced was from a mouse. Further, although mouse mutants have been the object of animal fanciers' fascination for centuries, the decoding of the mouse genome achieved in 2002 was possible because advances in mammalian gene manipulation technology (first recombinant DNA, then the gene "knock-out" technique) combined with significant material investments, dating all the way back to the beginning of the twentieth century, to preserve genetically known strains of this animal created by and used in cancer research and radiation genetics. Mouse work has even begun to revolutionize basic Mendelian assumptions, especially the notion that a gene's expression is independent of the parental origin of the chromosome.
Individual lives, however, are what connect larger structural shifts in the intellectual organization of science and the local modus operandi of research, and so it should not be surprising that I sustain my account of twentieth-century biology not through claims to institutional or organismic "greatness" but rather through more intimate knowledge of scientific biography. Thus I begin with and repeatedly emphasize the passion and drive of C. C. Little in the project of developing the inbred laboratory mouse. During his testimony before the 1965 congressional hearings on cigarette labeling, Little asked lawmakers if they comprehended why he was focusing so much on the animal that was the basis of his scientific claims about smoking and cancer in humans: "I have spoken of mice as the servant of man. Why is this true? What made its truth evident? In other words, why mice?" Little was then nearing the end of a long career dedicated to "building a better mouse" for research, and his final project was controversial: as head of the Tobacco Institute Research Committee (precursor to the contemporary Council for Tobacco Research), he advanced the hypothesis that certain cancers developed in animals only if they possessed a preexisting genetic susceptibility. Indeed, there was perhaps no one for whom these queries held more personal meaning or urgency. On his eightieth birthday, Little penned a cartoon that summed up his views of the mouse's scientific and institutional achievements: it showed a likeness of Little himself dwarfed by a statue of the "JAX mouse, 1929-1968." The mouse carried a sack of money-presumably that which JAX made through the sales of mice to researchers-and addressed its scientist-muse: "You've had 80 years! Look what my family has done in 39 years!" (fig I.5).
(Continues...)
Excerpted from Making Mice by Karen Rader Copyright © 2004 by Princeton University Press. Excerpted by permission.
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Table of Contents
Illustrations ix
Acknowledgments xiii
Abbreviations xvii
INTRODUCTION: Why Mice? 1
CHAPTER ONE: Mice, Medicine, and Genetics: From Pet Rodents to Research Materials (1900-21) 25
CHAPTER TWO: Experiment and Change: Institutionalizing Inbred Mice (1922-30) 59
CHAPTER THREE: Mice for Sale: Commodifying Research Animals (1930-33) 97
CHAPTER FOUR: A New Deal for Mice: Biomedicine as Big Science (1933-40) 135
CHAPTER FIVE: R X Mouse : JAX Mice in Cancer Research (1938-55) 175
CHAPTER SIX: Mouse Genetics as Public Policy: Radiation Risk in Cold War America (1946-56) 221
EPILOGUE: Animals and the New Biology: Oncomouse and Beyond 251
Bibliography 269
Index 293
What People are Saying About This
Engagingly written, Making Mice tells the story of the laboratory mouse and its diverse allies. It is a major contribution to the field.
— Susan Lindee, University of Pennsylvania
This energetic and elegantly written book represents a landmark study of the role of model organisms in the history of science. Blending biography, institutional history, and history of biology, Rader shows how mice came to feature so prominently in twentieth-century (and, indeed, twenty-first century) biomedical research.
— Angela N. H. Creager, Princeton University
This is a very engaging account of the rise of the mouse as a star of biomedical research during the twentieth century, and the central role C. C. Little played in 'selling' the mouse (in all senses of the phrase) to both scientists and the public.
— Lee Silver, Princeton University
"This energetic and elegantly written book represents a landmark study of the role of model organisms in the history of science. Blending biography, institutional history, and history of biology, Rader shows how mice came to feature so prominently in twentieth-century (and, indeed, twenty-first century) biomedical research."—Angela N. H. Creager, Princeton University"Engagingly written, Making Mice tells the story of the laboratory mouse and its diverse allies. It is a major contribution to the field."—Susan Lindee, University of Pennsylvania"This is a very engaging account of the rise of the mouse as a star of biomedical research during the twentieth century, and the central role C. C. Little played in 'selling' the mouse (in all senses of the phrase) to both scientists and the public."—Lee Silver, Princeton University
This energetic and elegantly written book represents a landmark study of the role of model organisms in the history of science. Blending biography, institutional history, and history of biology, Rader shows how mice came to feature so prominently in twentieth-century (and, indeed, twenty-first century) biomedical research.
— Angela N. H. Creager, Princeton University
Recipe
"This energetic and elegantly written book represents a landmark study of the role of model organisms in the history of science. Blending biography, institutional history, and history of biology, Rader shows how mice came to feature so prominently in twentieth-century (and, indeed, twenty-first century) biomedical research."—Angela N. H. Creager, Princeton University
"Engagingly written, Making Mice tells the story of the laboratory mouse and its diverse allies. It is a major contribution to the field."—Susan Lindee, University of Pennsylvania
"This is a very engaging account of the rise of the mouse as a star of biomedical research during the twentieth century, and the central role C. C. Little played in 'selling' the mouse (in all senses of the phrase) to both scientists and the public."—Lee Silver, Princeton University