REFLECTIONS ON IMAGE AND LOGIC: PHILOSOPHY AND 
THE HISTORY OF EXPERIMENTATION ON THE ROUS 
SARCOMA VIRUS IN THE EARLY TO MID 1900s 
 
 
 
 
 
 
 
by 
ININA KACHELMEIER 
 
 
 
 
 
 
 
 
 
 
A THESIS 
 
Presented to the Department of Philosophy  
and the Robert D. Clark Honors College  
in partial fulfillment of the requirements for the degree of  
Bachelor of Science 
 
June 2016 
An Abstract of the Thesis of 
Inina Kachelmeier for the degree of Bachelor of Science 
in the Department of Biology to be taken June 2016 
Title: Reflections on Image and Logic: Philosophy and the History of Experimentation 
on the Rous Sarcoma Virus in the Early to Mid-1900s 
Approved: _,./'_._C_t.._fA..'_L_,(,1/"---___ )_~ ___ _
Nicolae Morar 
When Rous published his experiments on transmissible chicken sarcomas at the 
beginning of the 201h century, laboratory research was just starting to grow more 
independent from the clinic. Later changes in the field and the growing emphasis on 
genetics meant that cancer came to be characterized not just as a physical phenomenon 
but also as a chemical and genetic condition within the body. I will begin my thesis by 
using Peter Galison's Image and Logic to introduce the topics of intercalated 
periodization, experimental image and logic traditions, and the utility of machines as 
loci of and participants in cross cultural exchange. I will then use the history of early 
experimentation on RSV as a model of scientific change. The interaction of virologists, 
cancer biologists, pathologists, bacteriophage researchers, experimental techniques, and 
technicians within experiments on RSV negotiated the importance of tumor virology to 
cancer research. Ultimately, I will show the emergence of distinct image and logic 
traditions within the early history of RSV, and I will discuss how images and logic 
represent fundamentally different modes of knowledge acquisition. 
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Acknowledgements 
I would like to thank Professors Nicolae Morar, Alan Kelly, and Daniel 
Rosenberg for their patience and help throughout the thesis process. I came to each of 
them as an eager CHC student and now leave, thanks to their guidance, as a thesis 
survivor. In particular I would like to thank Nicolae Morar for the continued support 
and philosophical knowledge which he imparted upon this biology student. Lastly, I 
would like to sing the praises of my parents, friends, and roommates for continually 
supporting me (and for dealing with my sleep addled brain). I could not have switched 
into the biology major at the end of my sophomore year and still graduated within 4 
years without the support of a community.  
  
  
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Table of Contents 
Introduction 1 Overview of Thesis Organization 3 
Chapter 1: Peter Galison’s Image and Logic and the Philosophy of Scientific Change 4 Introduction 4 1.1 Scientific Change Through Intercalated Periodization 5 1.2 The Importance of Technology 6 1.3 Image and Logic Traditions 7 1.4 Image and Logic and the History of Particle Physics 8 Conclusion 9 
Chapter 2: Cancer and Microbes in the Late-19th Century 10 Introduction 10 2.1 The Chamberland-Pasteur Filter 10 2.2 Origins of the Extrinsic Theory of Cancer Etiology 12 2.3 Rous’ 1910 and 1911 Experiments 14 Conclusion 21 
Chapter 3: Initial Rejection: Reactions to RSV in the Early 20th Century 22 Introduction 22 3.1 Limitations of Technology and Knowledge 23 3.2 A Move towards the Intrinsic Cancer Theory 26 Conclusion 31 
Chapter 4: Mid-20th Century Quantification Techniques 32 Introduction 32 4.1 The Phage School: Predecessor of Tumor Virology 35 4.2 Quantitative Assays for Tumor Virology 37 4.3 A Brief Overview of Subsequent work on RSV 41 Conclusion 43 
Chapter 5: Revisiting Image and Logic 44 
  
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Introduction 44 5.1 RSV and Trading zones 44 5.2 Image and Logic Devices 45 Conclusion 48 
Conclusion 49 
Bibliography 53 
 
  
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List of Figures  
Figure 1a-b. Microscopic images of the original chicken sarcoma (a) and of the 
intraperitoneal chicken sarcoma (b) 15 
Figure 2. Invasions of muscle by tumor cells of the original chicken sarcoma 16 
Figure 3. Summary of filtration and transplantation studies within the first eight 
generations of Rous’ chicken sarcoma 19 
Figure 4. The margins of metastasis from filtrate inoculated chicken no. 116 from 
generation 7A 20 
Figure 5. An RSV focus assay showing a 1:100 and 1:1000 dilution of virus stock 39 
Figure 6a-b. The relationship between relative viral concentration, foci number (a) and 
number of infected cells (b) using RSV 40 
 
 
  
  
  
Introduction 
What are the roles of experiment, theory, and technology in scientific change? 
At any one moment within scientific history we can identify a set of predominant 
theories (or systems of explanation which aim to provide a description of reality), 
methods, and technologies which are broadly utilized in or accepted by the scientific 
community. Peter Galison discusses the role that the disparate traditions of experiment, 
theory, and technology play in scientific change within his 1997 publication Image and 
Logic. Galison proposes a model of intercalated periodization as a schematic of 
scientific change. The term intercalated suggests the interaction of scientific groups 
without homogenization (“Reflections on” 1). In this model, scientific change is 
structured by the distinct rhythm of experimentation, theory, and technology. Overall, 
Galison argues that the interaction of these differing traditions is responsible for the 
strength and sense of progress within science.  
In Image and Logic Galison argues that machines are physical and ideological 
points of contact at which disparate scientific traditions interact. He organizes the 
history of particle physics around the tradition of image and logic devices. The image 
and logic tradition had distinct theories, technologies, and experimentation methods. 
Image and logic are also fundamentally different ways of looking at information. 
Images are immediate. They attempt to preserve information by maintaining form while 
logic seeks to locate meaning by analyzing the logical relationship between objects or 
ideas. In my thesis, I will explore the emergence of image and logic traditions within 
biology by analyzing the early history of the Rous Sarcoma Virus (RSV). I will also 
 
 
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show that this history is intercalated by discussing how the interaction of distinct groups 
of scientists led to the progression of research on RSV.  
In my thesis I will use RSV as a model of scientific change. The story of RSV 
begins in the early 1900s when Peyton Rous published two articles on sarcomas in 
Plymouth Barred Rock Hens. In the first, published in 1910, he characterized the 
isolated sarcomas and demonstrated that the tumor was transplantable to other chickens. 
In his second publication, Rous ground up isolated tumor cells and passed them through 
a Berkefeld filter, which prevents bacteria and cells from passing through. Rous found 
that he could induce tumor formation in subsequent chickens by injecting them with the 
filtrate. This indicated that cancer could be inducible by a still unknown “filterable 
agent.”  
Despite the later significance of RSV to our understanding of cancer etiology, 
Rous’ research was considered to be false or insignificant by mainstream cancer 
researchers for the majority of the early to mid-1900s. In 1966 Rous was recognized for 
his work on RSV when he was awarded a Nobel Prize in Physiology or Medicine 
alongside Charles Huggins. The 55 year period between when Rous discovered RSV 
and received the Novel Prize is the longest “incubation period” in Nobel Prize history 
(Weiss and Vogt 2353). I will analyze how scientific ideas about RSV changed over the 
course of a portion of those 55 years: the early to mid-20th century. I will show that the 
interaction of theory, experimentation, and technology within broader image and logic 
traditions was fundamental to research on RSV and to the development of a 
microbiological definition of cancer. 
 
 
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Overview of Thesis Organization 
In chapter 1 of my thesis I will discuss Image and Logic. In particular, I will 
focus on Galison’s conception of image and logic traditions within the history of 
particle physics, and the idea of intercalated periodization. In chapter 2 I will discuss 
how the relationship between bacteriology and (emerging) virology in the late 19th 
century led to the first definition of viruses and the extrinsic theory of cancer etiology. 
Then, in chapter 3, I will characterize the reaction of different groups of scientists to 
Rous’ experiment and to the extrinsic theory of cancer. I will explore how the ever 
increasing divide between mainstream oncologists and experimental pathologists led 
these two groups to different interpretations of Rous’ experiment. In this section I will 
also discuss how these groups developed unique image and logic traditions for 
researching cancer etiology. In chapter 4 I will focus on mid-1900s advances in 
experimentation practices (the focus and plaque assays) which led to further research on 
RSV. Finally, in chapter 5 I will return to Image and Logic and discuss the applicability 
of Galison’s philosophical framework to the history of RSV.  
 
 
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Chapter 1: Peter Galison’s Image and Logic and the Philosophy of 
Scientific Change 
Introduction 
Peter Galison explores the history of instrumentation in particle physics within 
his 1997 publication Image and Logic. In Image and Logic explores the social, 
theoretical, and experimental dynamics of particle physicists. Galison acknowledges 
that practitioners existed in a shifting scientific and social world. The Cold War would 
have a lasting impact on physics. In Galison’s words: “Statistics, weapons design, 
mathematics, nuclear physics all realign during the Cold War to form a new subject, 
simulations—at the same time a new category of physicist emerges, not quite 
experimenter and not quite theorist” (“Reflections on” 255). During this time, the 
structure of physics would also undergo a fundamental change. The 20th century would 
see the development of a collaborative scientific culture in which the teamwork of 
hundreds of physicists comes to replace individualistic experimentation (Zimer 289). 
Within this changing environment, Galison hones in on points of contact between 
disparate scientific subgroups..  
The philosophical importance of Image and Logic is in Galison’s recognition 
that physics is not one monolithic whole, but a conglomeration of diverse cultures and 
subcultures interacting with each other. Galison is interested in the relationship of 
scientific subsets to each other at points where they interact, and the relationship 
between these points of contact and culture at large. He ultimately argues that the partial 
autonomy of these separate groups (experiment, theory, and technology) is a strength of 
 
 
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the scientific community. His ideas concerning trading zones, intercalated periodization, 
and machines as cultural entities provide a relevant context for understanding the ways 
in which different sciences interacted within the development of experimentation on 
RSV.  
1.1 Scientific Change Through Intercalated Periodization 
Galison conceives of scientific change as a process of intercalated periodization. 
Different scientific subcultures such as technology, experimentation, and theory have 
their own rhythms. In Galison’s conceptual framework, big shifts or advancements in 
one subculture often do not coincide with changes in another. He uses the analogy of a 
brick wall in which the whole is made up of irregular breaks in the brick in order to 
illustrate this point and also to suggest that the incongruity between these subsets 
accounts for the strength and sense of progression within a science.  
Disparate scientific traditions interact at points of exchange which Galison calls 
trading zones. A central aspect of Galison’s intercalated periodization model is the 
interaction of differing scientific traditions. While groups have their own autonomy and 
differing rhythms of change, they also interact at points which Galison calls trading 
zones. Galison borrows the idea of trading zones from anthropology as a way of 
characterizing spatial, temporal, and symbolic regions where subcultures interact. 
Coordinate rules of exchange allows groups to trade despite vast global and local 
differences. Thus, groups will be able to trade despite differing conceptions of the value 
of the object in question. The ways in which these subcultures interact, what value they 
bring to each other, how they situate language, and how they relate to broader scientific 
culture is important to determining the outcome of trade. 
 
 
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1.2 The Importance of Technology 
Technology is important in these trading zones because it mediates the 
relationship between diverse subcultures. To technology, Galison endows the gift of 
aggregation: “By the material culture of science I have in mind the study of instruments 
as accretion points, loci where new worlds emerge through the recombination of 
physics, engineering, warfare, industry, philosophy, chemistry, and mathematics” 
(“Reflections on” 1). In section 6.1 of Image and Logic, Galison likens the central role 
of machines in cultural exchange to pidgins and creoles. He writes: “Objects draw 
together clusters of cultural practices the way pidgins and creoles bind languages” 
(Image and Logic 436). Thus, technology has a central role in bringing together 
different subcultures and binding these cultures to one another. Due to its localizing 
properties, technology itself acts as a trading zone.  
 Machines also participate in cross-cultural exchange by means of their own 
histories. They are not neutral units of exchange. On this Galison writes:   
“while it would be an error to suppose that machines can be plucked 
cleanly from their context, it would be equally distorted to assume that 
objects carry the totality of their culture embedded within them. One of 
the central arguments of this book is that there is a partial peeling away, 
an (incomplete) disencumberance of meaning that is associated with the 
transfer of objects” (Image and Logic 436).  
To borrow from his previous analogy, like a pidgin or creole machines are units of 
cross-cultural exchange both in the process of their creation (which may draw 
technologies or scientists from various fields) and in their use (which, again, often 
deviates from their original context and spans different contexts). This concept, that of a 
“partial peeling away,” will be important when thinking about experimentation in RSV. 
In my thesis I will show the transfer of experimentation techniques between 
 
 
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bacteriology, bacteriophage biology, and virology. In each of these iterations, the 
definition of microbes and of cancer will undergo substantial revision.  
1.3 Image and Logic Traditions 
Lastly, as is evident from the title of the book, in Image and Logic Galison 
explores the unique history of image and logic devices. He differentiates between 
instrument makers who produce image-making devices and makers whose devices 
would produce logic. These are two fundamentally different methods of knowledge 
transmission. Galison labels these as “homomorphic,” or preserving form, and 
“homologous,” or preserving logical relations. Historically, the antipositivists viewed 
images as emblems of the “ineffable, the tacit, the non-rational,” emblems of rebellion 
against the “science-as-rules” of a positivist scientific view (“Reflections on” 1). The 
idea here is that pictures are in some way pure because they attempt to capture the 
whole reality of a situation which is then interpreted in a variety of ways. Galison 
deviates from this argument and instead postulates that images are never unmediated. In 
his own words “by attending on anti-imaging alongside imaging, I aimed precisely to 
de-naturalize the visual, to make the production of visual data as historically, 
philosophically, and practically problematic as the generation of digital data” (1). A 
main focus of my thesis will be in analyzing the emergence of distinct image and logic 
traditions within the early history of RSV, and analyzing how these functioned as 
fundamentally different modes of knowledge acquisition.  
 
 
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1.4 Image and Logic and the History of Particle Physics 
The distinction between image and logic devices is central to the history of 
particle physics within the book Image and Logic. Galison traces the distinct lineage of 
image devices from C.T.R. Wilson’s 1911 cloud chambers, to photographic emulsion 
devices, to bubble chambers. These experimenters characterized the passage of particles 
at visualizable “golden moments” (Ziman 291). In contrast, another set of 
experimenters focused on “counters,” or quantifying the frequency of moments of 
passage (292). These two traditions would meet in the technological innovations of the 
1970s. Time projector cables (TPC) provided a three dimensional record of electronic 
passage such that the passage of particles was both imaged and statistically analyzed.  
By focusing on image and logic devices, Galison highlights the central role that 
experimentation has in scientific history. As John Ziman writes in his review of Image 
and Logic, the history of “twentieth century microphysics has been dominated by 
theoreticians, who write the story inwards from unifying theories” (289). Galison 
organizes history around experimentation instead of theory. Thereby, he is able to 
elucidate the ways in which experiments and machines create and engage with 
knowledge. By analyzing the lineage of image and logic traditions, Galison shows that 
different groups of scientists have fundamentally different ways of presenting, 
analyzing, and creating data. Thus, Galison’s analysis of image and logic represents a 
new way of thinking about scientific history. This methodology acknowledges the 
importance of looking at the ways in which knowledge is constructed and presented to 
the social and epistemic history of science.  
 
 
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Conclusion 
In my thesis I will explore how technological/experimental advancements in the 
20th century were sites at which disparate traditions in bacteriology, bacteriophage 
biology, genetics, and oncology established the importance of RSV to cancer research, 
where the definition of cancer and viruses were mediated, and where ultimately a 
unique scientific group focused on tumor virology established itself. To this end, I will 
use a historical approach. Galison wrote that histories must be “be dense and specific 
enough to understand the limits of the malleability of objects and meanings as they 
travel from domain to domain” (Image and Logic 357). I will use this approach because 
it will allow me to analyze the temporal configuration of differing scientific traditions, 
to exemplify the relationship between scientific experiments and social climate, and to 
analyze the lineage of experimental traditions through time. Ultimately, this approach 
also allows me to discuss the fundamental differences and applications of the image and 
logic divide.  
 
 
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Chapter 2: Cancer and Microbes in the Late-19th Century 
Introduction 
In this section of my thesis I will explore the intersection of bacteriology, 
virology, and cancer research in the latter part of the 19th century. The extrinsic theory 
of cancer (also called the parasitic, exogenous, or germ theory) is the idea that cancer is 
caused by microbes. The extrinsic theory became popular in the latter part of the 19th 
century after the recent clinical triumphs of bacteriology research opened the minds of 
mainstream scientists to the possibility that microbes could cause a variety of diseases, 
including cancer. Virology also emerged during this time period. Plant bacteriologists 
were the first to conceive of viruses when they found that certain cell-free filtrates 
remained infectious. The convergence of early work on bacteriology and virology 
formed the basis of the extrinsic theory of cancer etiology, and established the first 
definition of viruses as infectious organisms.  
2.1 The Chamberland-Pasteur Filter 
The development of the Chamberland-Pasteur filter in the latter part of the 19th 
century allowed scientists to separate bacteria and cells from filtrates and eventually led 
to the discovery of viruses. The Chamberland-Pasteur filter was developed by Charles 
Chamberland, then an assistant to Louis Pasteur, with the intention of “freeing the water 
in waterworks from micro-organisms” (“Chamberland’s” 410). The filter works by 
removing bacteria and cells that are too large to fit through the natural pores in the 
porcelain from the remaining liquid. According to reports from the time period, while 
this filter was impractical for use in the household due the arduous process of heating 
 
 
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and purifying the porcelain filtering-rods it did succeed in blocking the passage of 
bacteria, cells, and fungi (“Chamberland’s” 410).  
Viruses were first conceptualized in plant bacteriology experiments that 
stumbled upon the capability of cell-free filtrates to remain infectious. An 1892 
experiment by Ivanovskij was the first to demonstrate that the filtrate could induce 
disease in tobacco plants. However, it was Martinus Beijerinck in 1898 who 
hypothesized that the cause of the disease was a disease-inducing organism, which he 
named contagium vivum fluidum (contagious living fluid). In an effort to prove the 
existence of a living microbe, Beijerinck conducted diffusion experiments. At the time 
filtration experiments were still “open to criticism” (Beijerinck 35). By showing that the 
infectious material had the ability to diffuse through an agar plate and infect subsequent 
plants, Beijerinck validated his assertion that the infectious material was a living and 
not static entity. He concluded the following about what he alternatively called 
contagium vivum fluidium and a virus: they were soluble, they were infectious, they 
could replicate only on living tissues, and they were small. His experiment was soon 
followed by the identification of the first animal and human viruses: foot-and-mouth 
disease virus and yellow fever virus (Javier and Butel 7694).  
The emergence of research on viruses happened at a time when scientists were 
reconceptualizing the relationship between microbes and humans. The germ theory of 
disease, the idea that diseases are caused by microbes, was put forth by Louis Pasteur in 
1867. Pasteur, a chemist by training, had previously shown that different 
microorganisms are associated with different kinds of fermentations and that a disease 
in silkworms was caused by microorganisms. Robert Koch’s subsequent work on 
 
 
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anthrax established the experimental framework of isolation, infection, and re-isolation 
for determining that a germ was responsible for a disease. Though initially rejected by 
many physicians, the germ theory proved useful as it eventually led to the identification 
of agents responsible for dysentery, cholera, and rabies among other diseases (Weinberg 
42; Tsoucalas et al 519). These developments were recognized by doctors who, though 
wary of the benefit of laboratory science, acknowledged the clinical significance of 
these findings. In 1883 doctor William T. Belfied wrote in a review that: “Illness may 
be caused by the not living products of putrefactions, as well as by the living organisms 
which abound in and probably produce putrefactions. But in the latter case the disease 
may be farther expended to fresh, healthy individuals by infection: in the former it 
cannot be” (Belfied 134). Belfied’s quote exemplifies the recognition of clinicians that 
“living” and “infectious” organisms could cause disease. At the same time, Belfied’s 
emphasis on the pathology of viruses that infect “fresh, healthy individuals” suggests 
that bacteriologists and virologists had a fundamentally different relationship to 
microbial research. While clinicians and mainstream oncologists were interested in the 
relevance of such research to medicine, researchers were interested in determining 
characteristics of and defining these microscopic organisms.  
2.2 Origins of the Extrinsic Theory of Cancer Etiology 
The success of early experiments on bacteria and their applicability to real 
disease cases opened the possibility that cancer, which was just beginning to become 
prominent in public consciousness, could also be caused by microbes. One of Pasteurs 
followers, Etienne Bernet, wrote in his 1907 publication La Lutte contre le microbes 
(The fight against microbes) that: “It is long discussed for cancer that heredity is a 
 
 
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legend that will vanish when contagion will be proved” (Tsoucalas et al 520). To 
support his adamant vote of confidence for the extrinsic theory and for the causality of 
all disease by germs, Bernet likens cancer to tuberculosis. He writes: “Cancer is almost 
to the point where tuberculosis was, when Villemin demonstrated contagion and 
inoculability….Cancer had its Villemin and waits for the discovery of its microbe; it 
waits for Robert Koch” (519). Bolstered by the recent success of Jean-Antoine 
Villemin, the scientist credited with showing that tuberculosis was infectious, and 
Robert Koch, who identified the causative agent of tuberculosis, it was not difficult to 
imagine that cancer could also be caused by a microbe.  
A number of subsequent experiments looked at the relationship between 
microorganisms and cancer. Initially, these experiments focused on bacteria and fungi 
and not on viruses. Such experiments included Scheuerling and Rapin’s 1887 and 1889 
experiments on intracellular microorganisms and the development of tumors; the 
microorganisms identified by Professor Charles Richet and (separately) Eugene Doyen; 
experiments on the influence of fungi on carcinogenesis; and eventually the sporozoite 
theory which postulated that sporozoites (a spore like stage in the lifecycle of some 
organisms) contaminated the air and food chain could explain cancer incidence in rural 
regions (520). In 1876 an experiment on canine venereal sarcomas by M.A. Novinsky 
showed that venereal canine sarcomas were transmittable across histocompatible 
barriers to foxes (“100 Years” 2352). These experiments largely failed to identify a 
definitive link between cancer and microbes, and their failures only served to suggest to 
other scientists that there was no link between the two. 
 
 
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In later experiments, scientists used filtration devices to show that cell-free 
filtrates could induce cancer in select organisms. In 1908 Ellerman and Bang conducted 
research on erythro–myeloblastic leukemias in chickens. They found that these 
leukemias were transmittable via cell free filtrates. Further research did not pick up 
because leukemias were not recognized as cancers until the 1940s and because the two 
researchers abandoned the project (Weiss and Vogt 2352; Van Epps 2013). In 1914 
Fujinami and Inamoto (working independently of Rous) isolated another chicken 
sarcoma which they later found was also transmittable by filtrate (Martin 7910). The 
most famous of these experiments was Rous’ 1911 experiment which, though not the 
only experiment to establish the transfer of cancer via filtrate, later identified the first 
virus recognized as a cause of cancer.  
2.3 Rous’ 1910 and 1911 Experiments 
2 years after graduating medical school, Peyton Rous became head of a cancer 
research laboratory at the Rockefeller Institute (Rubin 14389). In 1910 and 1911 he 
published articles on research he had done concerning sarcomas within barred Plymouth 
Rock hens. In this section I will discuss the various imaging and logic techniques which 
Rous’ used to characterize RSV. I will also analyze the utility of these two modes of 
knowledge retention within these early RSV experiments.  
In his 1910 experiment, Rous used imaging techniques to characterize the original and 
transplanted chicken tumors. In this experiment, Rous conducts transplantation studies 
by using a large trocar to implant bits of the tumor rim into the left breast muscle and 
peritoneal cavity of the same fowl (“A Tranmissible” 697). In the beginning of his 1910 
publication, Rous notes that “macroscopically, the growth suggested a sarcoma” (697). 
 
 
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However, Rous was unable to definitively confirm that the tumor was a spindle-cell 
sarcoma until he took microscopic images of sections of the tumor. 
 
Figure 1a-b. Microscopic images of the original chicken sarcoma (a) and of the 
intraperitoneal chicken sarcoma (b) 
These images (the first taken from the original tumor and the second from the 
transplanted growth) show that both tumorous growth are composed of narrow, 
elongated cells otherwise known as spindle cells (“A Transplantable” 707).  
Spindle-cell sarcomas are a type of cancer localized to the connective tissue in which 
the cells are “spindle-shaped,” or elongated. In figures 1a and 1b above, we see that 
microscopic images of the original and transplantable sarcoma both reveal that the 
(a) 
(b) 
 
 
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tumor is composed of narrow, elongated cells. These images confirmed that the original 
tumor was a spindle-cell sarcoma and that transplanted tumors retain spindle-cell 
characteristics. 
In his 1910 report, Rous also uses microscopy to demonstrate that the original 
tumor cells infiltrated surrounding tissue. Tumors are defined as cancerous if they have 
the ability to metastasize (or invade distant sites). Rous noted that the original tumor 
appeared to be benign (it was stationary or not invading surrounding tissue), however 
within tumor sections he identified points at which the tumor had begun to invade the 
surrounding muscle tissue.  
 
Figure 2. Invasions of muscle by tumor cells of the original chicken sarcoma  
In this image one can see that the original sarcoma cells are beginning to invade muscle 
cells.  
The infiltration of muscle cells by sarcoma cells can be seen in figure 2 above. The 
ability of these cells to metastasize means that Rous’ chicken sarcomas were cancerous 
and not benign.  
 
 
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In his 1911 publication, Rous expanded upon his earlier transplantation studies 
by demonstrating that the tumors were transplantable to other chickens, and used a 
Berkefeld filter to show that tumors were inducible via a cell-free filtrate. Rous had 
used imaging of the transplanted and original sarcoma to confirm that both were 
spindle-cell sarcomas. Following these results, Rous undertook an effort to determine 
the factor which made the cancer transplantable. He used the Berkefeld filter (a 
filtration device like the Chamberland-Pasteur filter but using a different type of 
porcelain) to isolate a cell-free filtrate. Rous later describes his use of the Berkefeld 
filter as a decision “made merely in line of scientific duty….Here was a new growth and 
in a new family and tests for its cause just had to be made” (Becsei-Kilborn 127-128). 
Rous was not expecting these filtration experiments to be successful. In the introduction 
to his 1911 publication, Rous writes:  
“In a careful study of the growth, tests have been made to determine 
whether it can be transmittable by a filtrate free of tumor cells. Attempts 
to so transmit rat, mouse, and dog tumors have never succeeded; and it 
was supposed that the sarcoma of the fowl would not differ from them in 
this regard, since it is a typical neoplasm” (“A Sarcoma” 397).  
Though not expected to do so, Rous’ found that RSV was transmissible by a cell-free 
filtrate. The results of Rous’ transplantation and filtration experiments are summarized 
in figure 3 below.  
Rous made several general observations from figure 3. First of all, successful 
transplantation largely depended on the character and condition of the host. 
Transplantation largely failed to grow in impure chickens (circles) except in later 
generations. Rous also observes in his report that the health of the chicken was a factor 
which influenced successful metastasis and tumor growth (404). Rous’ writes that the 
 
 
18  
importance of the aspects of the host (individual species and health) to tumor success 
had been used as “evidence against a specific cause for the disease, extrinsic of the 
cells” (409). The success of Rous’ filtration experiments, however, incited Rous to 
write that: “Such evidence is void, now that a growth has been found possessing the 
traits mentioned, yet transmissible independently of the cells” (409).  
 
 
 
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Figure 3. Summary of filtration and transplantation studies within the first eight 
generations of Rous’ chicken sarcoma  
The blackened symbols indicated tumors which grew in the host. The cross-barred 
symbols represent tumors which appeared but remained stationary or retrogressed. 
Clear symbols indicate tumors which did not grow at all. Rous used pure-bred 
(squares), impure bred chickens which were bought at random (circles), and other 
varieties of chickens of differing sort and appearance (triangles). The lines between 
generations indicate transplantation of the tumor from one chicken to others. Only the 
individuals of generation 7A (indicated by the red arrow) were not inoculated with a 
tumor segment but were inoculated by filtrate. The 8th E and D generations are 
therefore the only transplantations from the filtrate-inoculated tumor lines. The 9th B 
generation are chickens transplanted with tumor segments from the 7th or 8th generation 
which were omitted from this chart because conditions in them were “irregularly 
modified” (“A Sarcoma” 402).  
The second important trend visible in figure 3 is the ability of a cell-free filtrate 
to induce cancer. The majority of chickens within generation 7A (those inoculated by a 
cell-free filtrate) developed tumors. Furthermore, these tumors developed in chickens of 
both pure and impure heritage. Microscopic imaging of tumors from generation 7A 
were able to show that filtrate-inoculated tumors retained spindle-cell sarcoma 
characteristics, and were invasive (Figure 4).  
 
 
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Figure 4. The margins of metastasis from filtrate inoculated chicken no. 116 from 
generation 7A  
In this image once can see the invasion of the chicken sarcoma into muscle of the 
gizzard. 
Upon the observation that tumorous growths were inducible via a cell-free 
filtrate, Rous made several attempts to identify a parasitic agent. He attempted to grow 
the microbe on a cell-culture, and tried to image it using dark-field microscopy. 
However, as Rous writes, “[n]either this nor the various histological procedures applied 
to the neoplastic tissue has disclosed anything which can be recognized as a parasitic 
organism” (407). What would later come to be characterized as a tumor virus would 
remain essentially invisible during this time period. As Rous notes, histological 
techniques were largely unable to characterize viruses and it would take later 
developments in cell-culturing techniques before viruses became quantifiable.  
 
 
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Conclusion 
The early history of virology is highly intertwined with bacteriology. In the late 
19th century, virology became conceived of as an offshoot of bacteriology. It was during 
this time period that the extrinsic theory of cancer origin was born, and that scientists 
began to use filtration devices. In the latter part of this chapter I analyze the techniques 
used by Rous in his 1910 and 1911 publications. Rous used a variety of imaging and 
logic techniques to characterize the nature and growth of chicken sarcomas. Imaging 
techniques were able to confirm that both the original, transplanted, and filtrate-induced 
tumors were spindle cell sarcomas (Figures 1a-b, 2, and 4). These images are 
homologous, they preserve form. Rous followed the growth of tumors through 8 
generations of transplantation and filtrate-inoculation studies within figure 3. This chart 
is an example of homologous data, as it preserves logical relations and involves the 
accumulation of multiple data points. In this chart, Rous is able to show that the tumor 
was inducible by a filterable agent, possibly a microbe.  
Though Rous used the Berkefeld filter “merely in the line of scientific duty,” his 
results were born into a scientific culture defined by the divide between the extrinsic 
and intrinsic theory of cancer. In the next section of my thesis I will explore the reaction 
of laboratory scientists, mainstream oncologists, and clinicians to Rous’ research. I will 
also look at how the continued association of the extrinsic cancer theory with the failure 
of early tumor virology experiments, the vague and unsatisfying definition of viruses, 
and the incongruity between the infectious nature of microbes and the non-
infectiousness of cancer made mainstream cancer researchers skeptical of Rous’ 
experiment.  
 
 
22  
Chapter 3: Initial Rejection: Reactions to RSV in the Early 20th 
Century 
Introduction 
In this section I will discuss the reaction of various members of the scientific 
community to experimentation on RSV. In the early 20th century, the majority of 
mainstream scientific researchers in the US considered Rous’ research to be 
insignificant, irrelevant, or false. Many scientists doubted Rous’ experiment on the basis 
that his induced chicken sarcomas were not “true” tumors. Others contended that the 
filterable agent was a chemical or small bacteria and not a virus. As Peter Vogt points 
out, Rous’ filterable chicken sarcoma experiment was relatively irrefutable. Though 
many would acknowledge this, ultimately most mainstream scientists relegated Rous’ 
experiment “to the realm of interesting but basically irrelevant scientific curios, of no 
significance to the understanding of human cancer” (“Peyton Rous” 1559). In the 
following section I will explore how the divide between scientists who supported the 
extrinsic and intrinsic cancer theory delineated two experimental traditions: one focused 
on image and the other on logic. The logic tradition is largely epitomized by laboratory 
scientists while two groups within the cancer community, oncologists and clinicians, 
were interested in the image tradition. I will also discuss how the state of theory, the 
ability of technology to characterize viruses and cancer, and the state of knowledge at 
the time limited the potential for further work on RSV.  
 
 
23  
3.1 Limitations of Technology and Knowledge 
Becsei-Kilborn broadly classifies the main objections raised about the extrinsic 
theory and Rous’ experiment within her publication “Scientific reputation and scientific 
discovery.” Many scientists believed that the chicken sarcomas were not “true tumors” 
but were simply infectious growths called granulomas. In his 1911 report, Rous seems 
to anticipate this when he writes:  
“The above traits have figured largely in current discussions on cancer 
etiology, and most of them have been regarded as evidence against a 
specific cause for the disease, extrinsic of the cells. Such evidence is 
void, now that a growth has been found possessing the traits mentioned, 
yet transmissible independently of the cells. This fact, and not the 
problem of how to classify the growth, merits attention” (“A Sarcoma” 
409).  
Others believed that the cause of RSV was not a virus but a chemical component which 
had passed through the filter. Again, Rous makes himself open to this possibility in his 
paper. He writes: “an agency of another sort is not out of the question. It is conceivable 
that a chemical stimulant, elaborated by the neoplastic cells, might cause the tumor in 
another host and bring about in consequence a further production of the same stimulant” 
(“A Sarcoma” 410). It would be difficult to address these concerns without the 
advancement of more broadly accepted definitions of viruses and cancer.  
These arguments were exacerbated by the limitations of knowledge about what 
viruses and cancer were. Rous recounts the reaction of one British oncologist who told 
him: “But, my dear fellow, don’t you see, this can’t be cancer because you know its 
cause” (Martin 2004). In a review published in Science, another pathologist writes that 
“cancer is probably caused by some change, perhaps a chemical change, which the 
human body undergoes in the course of years” (Wolff 1925). The extrinsic theory of 
 
 
24  
cancer is fervently rejected in the review, and Wolff says “There is no such thing as a 
cancer germ. There can be none” and he goes on to postulate that the lack of potassium 
suffered by “civilized human[s],” a theme belayed by racial undertones, “is one of the 
factors, if not the main factor, in the occurrence of cancer” (Wolff 1925). These reviews 
exemplify the pervasive lack of knowledge about cancer and virology. As Becsei-
Kilborn writes, “[s]cientific publications on cancer were largely based on hypotheses 
and cancer research lacked a sense of direction” (Becsei-Kilborn 118). There was little 
knowledge about what viruses, much less cancer, were. Terms such as “parasite,” 
“germ,” and “virus” were used interchangeably (119). The ever shifting language made 
it difficult for scientists to hold concrete discussions about whether or not Rous’ 
sarcoma’s were “true” tumors and whether or not viruses could cause cancer. 
The origins of virology within bacteriology also led to skepticism about whether 
or not viruses existed. In “The discovery of viruses: advancing science and medicine by 
challenging dogma,” Andrew Atenstein discusses the impact that the germ theory of 
disease and “Koch’s postulates” had on virology. Koch’s postulates were rules for 
proving the microbial etiology of a specific disease. Koch developed them during the 
time period in which he was working on tuberculosis (Artenstein 470). The postulates 
were as follows: (1) the pathogen can be identified in all cases of the disease; (2) the 
pathogen is not present in healthy individuals; (3) the pathogen must be able to induce 
the disease in animal models after isolation and passage through a pure culture (Byrd 
and Segre 224). Viruses did not fit Koch’s criteria. Biejerinck and Ivanovski were able 
to show that viruses could induce disease but, because viruses passed through filtration 
devices, researchers were unable to prove that they were not chemicals or small bacteria 
 
 
25  
(Artenstein 471). It was not until the 1950s that virology began to establish itself as a 
distinct and prominent science. Around this time, several virology journals established 
themselves and the first virology textbook was published (“When did” 142). It was not 
until the end of the first quarter of the twentieth century that scientists would 
definitively establish that viruses existed, and debate over the nature of viruses would 
continue long past that (472).  
Still others were skeptical that chicken sarcomas could have any relevance to 
human cancer (Becsei-Kilborn 115). There were several incongruences between the 
idea that cancer was caused by microbes and what was known about cancer at the time. 
As Darwin Stapleton argues in Creating a Tradition of Biomedical Research, 
understanding the relationship between cell and virus was fundamental to debates about 
the extrinsic theory. While the filterable agent appeared to incite disease, “its behavior 
depended purely on the neoplastic cells themselves” (Stapleton 195). Experimentation 
on RSV had concluded that the virus did not spread epidemically among the chickens, 
and that metastasis was a result of migration of transformed cells and not a virus (195). 
In addition, experimentation done during the 1920s concluded that carcinogenic factors 
such as X-rays and coal tar could induce cancer. Until evidence that multiple exogenous 
and endogenous factors could contribute to cancer growth, scientists struggled to 
understand how carcinogenic factors and viruses could both lead to cancer. In this time 
period scientists assumed that for the extrinsic theory to be accurate, a virus would need 
to be present throughout the body in an inactive state. The virus would need to be 
activated upon association with another extrinsic element (Sankaran 193-200).  
 
 
26  
Rous and his coworker, Murphy, believed that the only way to show that RSV 
was alive would be in vitro propagation. However, this was impossible because cell 
culturing techniques were not yet advanced enough. As American virologist Thomas 
Rivers pointed out in 1932 that for the majority of the 20th century viruses were 
characterized by negative properties (Sankaran 192). As historians Waterson and 
Wilkinson write, viruses “were not retained by bacteriological filters; they could not be 
seen in the light microscope; and they could not be grown on artificial media” 
(Sanakaran 192; Rivers 78). Until further technological innovation happened in the 
1940s and 1950s, viruses were un-capturable: they avoided both visibility and 
quantification.   
3.2 A Move towards the Intrinsic Cancer Theory 
Debates about the validity of Rous’ experiment and work on tumor virology in 
general often centered on the divide between the intrinsic and extrinsic theory of cancer 
etiology. Mainstream cancer research began to move away from the extrinsic theory of 
cancer etiology in the early 20th century. H.G. Plimmer, a scientists working in the early 
1900’s who was a proponent of the extrinsic (or parasitic) theory, wrote in his 1903 
report on the origins of cancer: “the battle around cancer still rages. Is it parasitic or not 
parasitic?” (Plimmer 1511). Though adamant that the “parasitic theory is by no means 
yet extinct,” he concedes that “some would have us believe so” (1511). In reality, the 
theory was on its way out and by the end of 1910 Plimmer would have been one of a 
group of scientists that William Pusey identified as a “small but aggressive school of 
men which regard [cancer] as of infectious origin” (Becsei-Kilborn 122). Pusey goes on 
to suggest that as the extrinsic theory was losing validity with mainstream science, the 
 
 
27  
intrinsic theory was becoming more popular. He writes “the weight of opinion, 
however, is strong that it is a disease due to the intrinsic disturbance of the affected 
individual” (122). Pusey, like other mainstream cancer organizations and clinicians, was 
moving to the belief that cancer was caused by intrinsic disturbance, not extrinsic 
elements.  
From a theory perspective, Rous’ experiment conflicted with the predominant 
focus of mainstream cancer biology on intrinsic or tissue-specific causes of cancer. 
Rous’ experiment was published one year after a correspondence from the 1910 
International Conference on Cancer in Paris affirmed that the mass of evidence 
supported the view that “cancerous tissue is really a biological alternation of the tissue 
proper to the individual attacked by the disease, and thus its peculiar properties may be 
explained without assuming the intervention of extraneous agencies, such as a 
hypothetical cancer virus” (111-112). Rous’ publication put him on the losing side of a 
“battle” between extrinsic and intrinsic. 
The distinction between extrinsic and intrinsic didn’t exist only in the vague 
realm of theory or paradigm. It also manifested itself physically in the divide between 
different subsets of scientists. Historian Neeraja Sankaran writes in her article “When 
viruses were not in style” that physicians tended to favor the intrinsic theory of cancer 
etiology because it was clear to them through personal experience that cancer was not 
infectious. In contrast, laboratory pathologists interested in infectious diseases tended to 
favor the extrinsic theory, or at least recognize it as worthy of further research 
(Sankaran 194).  
 
 
28  
In public discourse on Rous’ experiments, laboratory scientists and clinicians 
were negotiating not only the value of Rous’ experiment but also the nature of scientific 
research. The “lack of interface” between laboratory and clinic is a commonly 
emphasized area of tension for research in the early half of the twentieth century 
(Becsei-Kilborn 115). Scientists who supported research on RSV and the parasitic 
theory advocated for a more experimental approach to research, instead of the more 
common morphological approach. As British virologist Christopher Andrewes writes: 
“The virus theory has had its ups and downs, mostly downs, for pathologists in general 
have not regarded it favorably. On the other hand, many bacteriologists, and particularly 
virus workers, are impressed by arguments in its favor” (Sankaran 193). This 
fundamental difference is explored in Darwin Stapleton’s work “Creating a Tradition of 
Biomedical Research.” Erwin Smith, an experimental plant pathologist, is credited in 
the proceedings of the second Pan American scientific congress held in 1915 as writing:  
“I do not mean to condemn the study of sections, but only to suggest that 
there are also other ways of looking at this problem, which is one of 
growing things. There is too much reasoning in a circle on the part of 
many of these writers, too much argument basing one assumption on 
another assumption as if the latter were a well-established and solid fact, 
too little clear thinking of a biological sort, too little first-hand 
knowledge of living plants and animals, too much dogmatism, too much 
orthodoxy, and not enough experimentation. Hence the pessimism and 
the discouragement….These strong men, chiefly morphologists, have 
dominated the situation for a generation, but they have not explained 
cancer and they can not explain it, and they must now give way” 
(Stapleton 197-198)  
Smith, whose scientific work established that the crown galls in plants retained tumor-
like characteristics, was advocating for the usefulness of laboratory science not just in 
providing a cure for disease, but for understanding disease. On the other side of the 
divide were those like Victor Schmieden, a prominent surgeon, who said this of later 
 
 
29  
research on RSV: “It is alien to the clinician’s mode of thinking not to rely on 
conclusive evidence from human materials….[W]e must warn against attaching too 
much value to comparative observations from the animal or plant kingdom” (Stapleton 
198). Though Erwin is an extreme example of what Becsei-Kilborn would classify as 
“one of those few clinical researchers who had strong reservations about the benefit of 
animal experimentation for medicine,” clinicians nevertheless often displayed distrust 
for bacteriology labs (Becsei-Kilborn 115).  
 In contrast to the virologist’s world of filtrates, a morphological approach to 
cancer research had developed its own experimental techniques. The intrinsic theory of 
cancer (otherwise called the biological view) grew in popularity over the first decade of 
the 20th century. Cancer “was increasingly regarded as a local condition due to chronic 
irritation and chemical carcinogenesis” (Becsei-Kilborn 121). Transplantation studies, 
in which tumors were isolated and transplanted to other places/organisms, and the study 
of tumor sections under a microscope were favored in mainstream research. In an essay 
from the proceedings of the Second Pan American Scientific Congress, Erwin Smith 
writes that “cancer morphologists have patiently cut and stained and studied hundreds 
of thousands of tumors, refining and refining their definitions and distinctions and 
building up high walls of separation where nature has made none” (Swiggett 487). In 
Smith’s view, these techniques captured but a snapshot in the life of a tumor and were 
unable to adequately depict the “plasticity of living, growing things” (487). On the other 
side of this debate, clinicians also did not understand the practicality of tumor virology 
experiments. As has been explored above, research on the microbial origin of cancer 
was considered to be insignificant.  
 
 
30  
The approach of mainstream cancer research in the early 20th century epitomizes 
what Galison calls morphological scientists, or those who (he quotes John Merz here) 
“look upon real things not as examples of the general and universal, but as alone 
possessed of that mysterious something which distinguishes the real and actual from the 
possible and artificial” (Galison 79; Merz 203). The divide between extrinsic and 
intrinsic delineated two definitions of cancer: one physical and directly observable, the 
other relegated to the vague and unseen realm of filtrates and viruses. Unlike bacteria, 
viruses were invisible to light microscopes and unable to be cultured outside of the 
body. They remained largely unseen until the later development of electron microscopy. 
The inability of researchers to “see” viruses meant that quantifiable or “logic” 
experiments were the only ways that virologists could continue research on them. The 
divide between clinician and an emerging group of laboratory scientists was not only 
between extrinsic and intrinsic, but also between different modes of knowledge 
acquisition: one homomorphic and the other homologous.    
 
 
31  
Conclusion 
Peter Vogt, a molecular biologist, virologist, and geneticist, perhaps summarized 
it best when he wrote: in “the early 1900s, there was a lack of appropriate techniques 
for studying the fundamental aspects of viral oncogenesis, and the scientific attitudes 
prevalent during this time were not conducive for the kind of analysis that was needed” 
(Vogt 2010). Theory, experiment, and technology did not line up in such a way that 
Rous’ data was reconcilable with the search for cancer’s origin in intrinsic aspects of 
the cell. In the following section I will discuss the development of the plaque and focus 
assays. These quantification assays made it easier for virologists to count viruses, and 
led to the expansion of tumor virology. 
 
 
 
32  
Chapter 4: Mid-20th Century Quantification Techniques 
Introduction 
By the mid-1950s two of the major scientific concepts that were required to 
understand the behavior of RSV had already been established. First, research 
established the role of nucleic acids in the transfer of genetic information. Evidence for 
this was supported by work in genetics by Avery, MacLeod, and McCarthy as well as 
Watson, Franklin and Crick (who determined the structure of DNA). The second was 
the concept that viral genomes could become integrated into the cell genome, which 
was developed by Lwoff (“The DNA Provirus Hypothesis” 1075). This section of my 
thesis will look at the influence that quantification assays had on RSV research during 
the same time period.  
Research in the 1930s and 1940s had also established that filtrates could induce 
cancer in other animals (Lucke 1938; Shope 1932; Shope 1933; Bittner 1936) and that 
various papillomas, warts, and other growths in humans and other animals were 
transmissible by filtrate (Gross 1962). The possibility that an extrinsic microbial agent 
had a role in cancer once again appeared plausible. Edward Shrigley, a microbiologist, 
wrote about the increasing interest in viral particles in a 1951 review: “appreciation of 
the fact that viruses or virus-like agents may possess the ability to elicit growths in 
animal tissues is entering the thinking of an ever-widening circle of modern 
oncologists” (Shrigley 241). Affinity for the microbe hypothesis was due, in part, to a 
newly emerging consensus that there was no one cause of cancer. A variety of intrinsic 
and extrinsic causes, some supported by experiments listed above, including “chemical 
 
 
33  
carcinogenic agents, heredity, hormones, milk factors, viruses, physical trauma, and 
precancerous conditions” had been associated with cancer (Stowell 286; Sankaran 195-
6). Tumor virologists were no longer trying to prove that a microbe could be the cause 
of cancer, but simply that a microbe could be a factor in cancer etiology.  
 The 1940s and 50s also engendered a change in the definition of viruses. 
Though scientists had been working on characterizing viruses during preceding 
decades, in “When did virology start” Ton Van Helvoort argues that the “birth” of 
virology happened in the 1950s. Van Helvoort postulates that the emergence of virology 
as a promising discipline happened for two reasons. First, the identification of viral 
lysogeny (one of two modes of viral replication, it involves the integration of the viral 
genome into the host’s DNA) definitively proved the difference between bacteria and 
viruses. Second, lysogeny experiments established a new definition of viruses that 
unified research on animal, plant, and bacterial viruses (“When did” 142). The new 
definition of viruses was important for confirming that sarcoma agents and 
bacteriophage were viruses and not chemicals or small bacteria. In a separate 
publication, “History of virus research in the twentieth century,” Van Helvoort argues 
that the concept of filterable viruses “was deconstructed” in the 1930s and 1940s 
(“History of” 189; Sankaran 194). The belief that sarcoma agents and bacteriophages 
were not viruses had been established only “in relation to the paradigm of bacteriology, 
which interpreted infectious agents as autonomous living microbes” (“History of” 186; 
Sankaran 194). As early as the 1930s, mainstream virology researchers began citing the 
sarcoma agent as a virus (Sankaran 194). The re-establishment of the sarcoma agent as 
 
 
34  
a virus and the increasing acceptance that cancer could be caused by a variety of 
extrinsic or intrinsic agents led to renewed interest in tumor virology.  
In “When viruses were not in style” Neeraja Sankaran builds upon Van 
Helvoort’s analysis of lysogeny experiments. She makes a powerful argument for the 
importance of these experiments in establishing a link between virology and cancer. 
Sankaran demonstrates the pivotal role that experiments on lysogeny had in implicating 
bacteriophage (viruses that invade and replicate within bacterial cells) as agents of 
genetic change. In 1928 Burnet and Wollman proposed the idea that bacteriophages 
were genes that could be transmitted from cell to cell via an external nucleus. Though 
not initially popular, this theory was revived again in the 1950s by Lwolff (Sankaran 
196). According to Sankaran, Lwoff’s research “opened up avenues of research by 
offering a new way of thinking about viruses and their relationship to their hosts” 
(Sankaran 196). In 1953 Lwolff proposed that the “potential power of a cell to become 
malignant may be perpetuated in the form of a genelike structure….and that 
carcinogenic agents induce the expression of the potentiality of this genetic material” 
(Lwolff 14). These experiments established a new molecular understanding of viruses, 
and proved that viruses could become part of the cellular genome. 
While these theoretical advances pushed research on tumor virology towards a 
deeper understanding of the relationship between bacteriophage and genetics, there is a 
parallel history of technological advancement that further engendered the relationship 
between cancer research and tumor virology. This tradition begins, again, with 
bacteriophage research that established the first quantification assays for tumor viruses. 
The isolation of the bacteriophage by F.W. Twort and Félix d’Herelle, and the 
 
 
35  
subsequent “phage school,” was the technological and intellectual predecessor to later 
work on tumor microbiology.  
4.1 The Phage School: Predecessor of Tumor Virology  
Twort was the first to discover phage, or small agents that infect and kill 
bacteria. D’Herelle independently made the same discovery in 1917 while he was an 
unpaid intern at the Pasteur Institute. D’Herelle found an “invisible, antagonistic 
microbe of the dysentery bacillus” which formed clear spots in his cultures (Dublanchet 
16; Summers 131). For d’Herelle the bacteriophage was a living entity; it was “a 
parasite, a virus which penetrated into the sensitive bacteria” (Lwolff 274). At that time, 
scientists were concerned with proving whether or not viruses were living entities. 
William Summers writes in his article “The strange history of phage therapy” that 
viruses and phage occupied a “murky position” in scientific discourse “at the borderline 
of life” (Summers 132). They could be crystalized, which according to organic 
chemistry would indicate that they were chemicals. However, they could also mutate 
and multiply which implied that they were “somehow beyond chemistry” (132).  
Much like with RSV, bacteriophage had a complicated relationship to clinical 
biology. According to Lwolff, the response to d’Herelle’s work was “generally 
indifferent” with “opinions on d’Herelle ranging from visionary to fool” (Lwolff 16). 
Summers discusses three reports on bacteriophage done by the American Medical 
Association (AMA), writing that all three reports “exhibited the tension between 
laboratory study of phage therapy and its clinical applications, and between in vitro and 
in vivo action of phages on bacteria” (Summers 132). During the mid-1900s, medical 
practice was conducted by individual general practitioners and physicians who did not 
 
 
36  
have access to bacteriological labs. Though proven to be effective, bacteriophage 
therapy never became as widely used as antibiotics in mainstream medicine in the US. 
This was in part due to the easier shelf life of antibiotics, the association of 
bacteriophage with the Soviet Union and Germany during World War II (whose armies 
utilized phage therapy), and the advent of large pharmaceutical companies who wished 
to market “wonder drugs” instead of phage (Summers 131-132). The phage school did, 
however, pioneer experimental techniques which would prove useful for research on 
RSV.  
D’Herelle’s early experiments led to the development of a quantitative assay for 
bacteriophage. In 1917 d’Herelle originated the plaque assay technique. He writes:  
“if one adds to a culture of Shiga as little as a millionfold dilution of a 
previously lysed culture and if one spreads a droplet of this mixture on 
an agar slant, then one obtains after incubation a lawn of dysentery 
bacilli containing a certain number of circular areas….these points 
cannot represent colonies of the anatogonistic microbes: a chemical 
substance cannot concentrate itself over definite points” (Goldman 93) 
The plaque assay quantifies viruses by exploiting the ability of viruses to lyse (kill) 
bacteria. It is used to determine the concentration (titer) of viruses in a sample. A virus 
is introduced to a monolayer (or sparse layer) of bacterial cells. Then, the plate is 
covered with a nutrient medium and incubated. The titer of viruses is estimated by 
counting the number of plaques (or circular zones of clearing resulting from the phage 
lysing the bacterial cells) (Panec and Katz 2006). Following its introduction, the 
technique was refined by Gratia, Hershey, and colleagues. Using this technique, 
bacterial researchers were for the first time able to calculate the titers of bacteriophage 
stocks.  
 
 
37  
Further research done on bacteriophage by Mack Delbruck and Salvador Luria 
(among others) helped pioneer a biochemical approach to virology research. In 1940, 
Delbrück started the Cold Spring Harbor Phage Course. Delbrück, trained as a 
physicist, is described as a researcher with a “missionary devotion to bacteriophage 
biology” who believed that “the only biology was ‘quantitative biology’” (Susman 
1101). Peter Vogt characterizes the new phage school as delineating a new quantifiable 
approach to virology research:  
“[t]he idea of viruses as model biological organisms, the challenges to 
understand viral replication, to define the role of the host cell, the strictly 
reductionist strategy that concentrated on the single cell and the single 
viral particle—all of these marked a new way of thinking about 
biological problems” (Vogt 7)  
The phage school and the new quantitative assays exemplified a new laboratory-based 
methodology for isolating and characterizing viruses, and was part of an emerging 
experimental culture that further delineated itself from clinical research.  
4.2 Quantitative Assays for Tumor Virology 
The creation of a plaque assay for animal virology happened after further 
developments in cell culturing techniques enabled scientists to grow tumor cells in vitro 
(outside of the body). In 1955 Harry Eagle described the first defined media that could 
support the growth of animal cells. While it is relatively simple to culture bacteria and 
yeast, animal cells require a more complex culture media. The development of new cell 
culturing techniques was an important step in biomedical research as it allowed 
researchers to study mammalian tumor cell growth in vitro under a variety of controlled 
conditions (Herzenberg and Herzenberg 687-688). Renate Dulbecco modified the 
bacteriophage assay for use in animal virology (Panec and Katz 2006). Peter Vogt 
 
 
38  
describes the development of the animal plaque assay as “an almost direct transfer of 
phage technology to animal cells and animal viruses” (Vogt 7). He also credits the 
plaque assay as “the origin of experimental cellular virology and, ultimately, of today’s 
molecular virology” (7). The animal plaque assay made it possible for the first time to 
study neoplastic transformation and carcinogenesis in vitro.  
In 1958, Temin and Rubin developed a cell culture-based assay for virus-induced 
transformation called the focus assay (Vogt 8). To do this they used the Bryant strain of 
RSV, which cannot produce infectious progeny. Though methodologically related to the 
plaque assay, the focus assay was an important development as it did not quantify cell 
killing but rather the ability of a virus to induce cell aggregation (later this would be 
identified as oncogenic transformation). Work done with the focus assay inherently 
dealt with the ability of tumor viruses to induce cancerous transformation. In a focus 
assay, the transformative potential of a virus is determined by the accumulation of foci 
that develop on a cell culture upon introduction of a virus. When a tumor virus is 
applied to a cell culture, cells which become oncogenically transformed will replicate 
faster and form a distinguishable “focus” (or pile of cells). The correlation between viral 
concentration and foci accumulation visible in figure 5 below indicates that there is a 
positive relationship between the number of viral particles and the number of 
transformed cells (Figure 5).  
 
 
 
39  
 
Figure 5. An RSV focus assay showing a 1:100 and 1:1000 dilution of virus stock  
Experiments used a chick embryo fibroblast monolayer. The plate on the left had a 
1:100 dilution of virus stock while the plate on the right was diluted by 1:1000. Each 
dot on the plates represents a focus of transformed cells (“100 Years” 2353).  Temin and Rubin used the focus assay in order to model the relationship between virus concentration and number of foci as well as virus concentration and number of infected cells. In figure 6a below we see that there is a positive linear relationship between viral concentration and number of foci. This figure is an extension of the results we saw in figure 5 but presented in graph form. In Figure 6b, the researchers also quantify the relationship between foci development and cell transformation. They indicate that there is a positive relationship between the virus concentration and the number of infected cells until the upper threshold of 0.5% of infected cells is reached (Figure 6b). While Temin and Rubin acknowledge that their method for determining the number of infected cells is not highly accurate, nevertheless this experiment shows that early experiments on the foci assay linked RSV to cancerous transformation (“Characteristics of” 681).  
 
 
40  
 
Figure 6a-b. The relationship between relative viral concentration, foci number (a) and 
number of infected cells (b) using RSV 
Graph 6 (a) Virus concentration ranged from 1/80 and 1/2560 of stock. Foci were 
counted 5 days after infection. (b) Virus concentrations ranged from undiluted to 1/512 
of stock. Virus stock was placed on a culture for 30 minutes. Cultures were washed, 
trypsinized, and layer with various dilutions of infected cell suspensions. After 16 
hours, agar was added. Plates were counted 6 days after infection (“Characteristics of” 
680-681). 
Philosophically, the focus assay is a large departure from previous work on 
RSV. The focus assay was able to definitively establish the link between RSV and 
oncogenic transformation. In the words of Howard Temin, these cell culture assays 
“established that RSV by itself could transform cells and that it transformed fibroblastic 
cells” (“Neoplastic Transformation” 15). The focus assay was a turning point for tumor 
virology. Originally scientists were trying to determine whether or not tumor viruses 
(a) (b) 
 
 
41  
were living, whether or not they caused “true” cancerous growths, and how they were 
significant to human cancer cases. These were concerns expressed about RSV. With the 
introduction of the focus assay, the question now becomes: how do tumor viruses 
induce cancerous growths? 
As Howard Temin writes, ultimately the quantification assays “opened the way 
to the research that has now defined reverse transcription, oncogenes, and proto-
oncogenes and has shown that the fundamental connections between retroviral 
carcinogenesis and all other carcinogenesis” (15). Now, I will briefly outline the 
contribution of later work on RSV to our current understanding of cancer. This later 
history outlines the legacy of RSV research after the focus and plaque assays, and the 
role of RSV in a microbiological understanding of cancer.  
4.3 A Brief Overview of Subsequent work on RSV 
In their article “100 years of the Rous sarcoma virus,” scientists Robin Weiss 
and Peter Vogt discuss the fundamental role that research on RSV has had on our 
current understanding of cancer growth. In particular, they look at how research on 
retroviruses (viruses which use the reverse transcription of RNA to DNA in order to 
incorporate their DNA into a host’s genome) led to the discovery of oncogenes. 
Oncogenes are genes that have the potential to cause cancer. In human cancers, they are 
often mutated or overexpressed versions of normal growth regulatory genes (also called 
proto-oncogenes). When mutated they cause uncontrolled cell growth/division and lead 
to tumor formation. For example, ErbB2, P13KCA, MYC, and CCND1 are genes often 
deregulated in human breast cancer cases (Lee and Muller 2). The inactivation of 
tumor-suppressor genes, or genes that limit cell growth, can also lead to tumor 
 
 
42  
formation. To again use breast cancer as an example, in hereditary breast cancer cases 
mutations in the now well-known tumor suppressor genes BRCA1 and BRCA2 are 
associated with an elevated risk of breast and ovarian cancer (Lee and Muller 2). These 
are now commonly accepted causes of tumorigenesis. 
Research on RSV was fundamental to the discovery of retroviruses and 
oncogenes, and to the importance of genetic mutations in cancer growth. RSV was the 
first retrovirus to be recognized as a cause of cancer, and src, the mutated gene within 
RSV that is responsible for tumor formation, was the first identified oncogene. Research 
on RSV began to pick up after the introduction of the plaque and focus assays. RSV, 
once just a “filterable agent,” became recognized as a retrovirus in the 1960s. RSV 
stimulates uncontrolled cell division within its host, thereby inducing tumor formation 
through the incorporation of the src gene. In 1975 Michael Bishop and Harold Varmus 
showed that a normal (non-mutated) version of src (called c-src) is found in the genome 
of many species besides chickens, and promotes cell growth and cell division within 
normal cells. The viral src led to tumor formation because it was expressed at 
abnormally high levels within host cells (Chial 33). Research on RSV and src was 
pivotal for our understanding of oncogenes, and later research on DNA tumor viruses 
led to the identification of tumor suppressor proteins (proteins that suppress cell growth) 
(Weiss and Vogt 2352). Subsequent work has revealed the importance of somatic 
mutations (mutations which are not inherited but are later acquired by the cell) in genes 
which have the potential to become oncogenes and tumor suppressor genes to induce 
cancer growth. Research on RSV has thus had a pivotal role in the development of a 
molecular understanding of the mechanisms of cancer growth.   
 
 
43  
Conclusion 
 I mention these later developments in research in order to show the importance 
that RSV studies have had on our understanding of cancer. In this section of my thesis I 
have discussed the importance of viral quantification techniques to tumor virology. The 
interaction between the phage school and tumor virology was essential for the 
development of the plaque and focus assays. Furthermore, these quantification methods 
are the legacy of the logic tradition of research established by early laboratory scientists 
in bacteriology and virology. These techniques are in large part responsible for the 
importance of research on RSV because they proved that cancer and RSV were 
intimately linked and provided a way for researchers to elucidate this interaction. By 
looking at the impact of later research on RSV, one can see the lasting impact that these 
research traditions have had on our current understanding of tumorigenesis and cancer 
etiology.  
 
 
 
44  
Chapter 5: Revisiting Image and Logic 
Introduction 
Thus far I have organized my thesis by looking at the progression of thought, 
knowledge, and experimentation techniques in the early history of RSV. At the 
beginning of the 20th century, viruses existed as ineffable entities within filtrates. They 
were characterized by some as germs, as enzymes or as protein products. In the cell 
culture assays of the 1950s they became agents of oncogenic transformation and 
quantifiable microscopic entities. I have shown the lineage of work done on tumor 
virology. Tumor virology began with early work on bacteriology, progressed through 
the technological and theoretical advancements of the bacteriophage school, and 
eventually grew to occupy its own profession. In this section I will discuss the 
importance of the theoretical, experimental, and technological progression of RSV to 
our understanding of scientific change, and the theoretical underpinnings of image and 
logic devices.  
5.1 RSV and Trading zones 
The differing trajectories of experiment, theory, and technology within RSV 
suggest the applicability of the intercalated periodization framework that Galison 
presents within Image and Logic. A continuing theme within the history of RSV is the 
inability of technology, theory, and experiment to coordinate with the other. Often one 
subunit is “ahead” of another. For example, in the early 20th century filtration devices 
showed that viruses could induce cancer. The ability of RSV to cause tumors was not 
accepted, however, until the 1950s. Furthermore, the progression of thought on RSV 
 
 
45  
was a direct result of the interaction between different scientific groups. For example, 
the progression of knowledge on viruses and cancer, as well as the advent of viral 
quantification techniques, were contributing factors to the renewal of interest in RSV. 
Similarly, the plaque and focus assays for tumor virology were largely borrowed and 
amended from previous work by bacteriophage scientists.  
Experiments done concerning viruses and RSV were physical and metaphorical 
sites at which laboratory scientists and clinicians interacted. Often, these groups did not 
have the same understandings of the value of different developments. For example, 
while to bacteriophage scientists understanding the ability of phage to lyse bacteria was 
interesting unto itself, clinicians would largely be interested in these experiments for the 
potential of phage to be used as a therapy for bacterial illnesses. However, the value of 
concepts changed for different scientific subgroups. For example, research on RSV did 
not come to hold clinical significance until the advent of further advances in 
microbiological and genetic techniques showed the importance of mutation to cancer 
growth. In conclusion, the history of RSV affirms Galison’s notion that the interaction 
of different scientific subsets is important to the progression of scientific ideas and that 
scientists would negotiate the value of experiments at moments of exchange.  
5.2 Image and Logic Devices 
A central theme within the history of RSV has been the disparate history of 
image and logic devices among opponents and proponents of Rous’ experiments. The 
question is: why did some groups of scientists favor logic devices while others did not?  
Initially, logic devices were the only form of analysis available to laboratory scientists 
interested in RSV. Viruses escaped all forms of capture. Unlike bacteria they were too 
 
 
46  
small to be visualized by light microscopy, and could not be grown in culture. The 
advent of the plaque and focus assay allowed scientists to quantify and characterize 
tumor viruses, and to link their existence with cancer occurrence. The prominent role of 
logic devices in early RSV studies suggests the importance of such devices to the early 
history of microbiological research. Logic devices allowed scientists to go where the 
eye could not: inside the world of microscopic interaction.  
Throughout the history of RSV, image and logic experiments have provided 
researchers with differing ways to characterize cancer and tumor viruses. Microscopy 
was integral to Rous’ early experiments on RSV. Images of Plymouth Rock hen tumor 
sections proved that both transplantable, filtrate-induced, and original RSV tumors 
could be classified as sickle-cell sarcomas with invasive characteristics (Figures 1a-b, 2, 
and 4). However, it was only in logic experiments that Rous was able to preserve the 
existence and movement of RSV as a tumor virus. In logic experiments (Figure 3) Rous 
demonstrates the ability of a filterable agent to induce tumor formation in a majority of 
chickens. These data led Rous to postulates that cancer was inducible by a filterable 
agent. The development of quantification techniques in the 1950s continued the lineage 
of early logic experiments. The plaque and focus assays allowed scientists to quantify 
viruses and oncogenic transformation for the first time. The focus assay also established 
a definitive link between RSV and cancerous transformation. A close analysis of the 
way in which images and logic are used in these experiments reveals the utility of early 
logic experiments to the development of tumor virology.  
The divide between image and logic represents two fundamentally different 
methods of knowledge retention. Images, for example of tumor sections, are meant to 
 
 
47  
retain the form of an object in all its complexity. Images are instantaneous, they 
represent the physical features of an object at a given moment in time. Images of tumors 
defined early concepts of what cancer was and what it was not. Clinicians and 
oncologists used images to define whether or not a tumor was cancerous and to 
determine the cellular origin of cancer metastasis (tumors that have spread outside the 
boundaries of the original tumor site). The history of RSV also suggests some of the 
limitations of images. In research on RSV, images were associated with a biological 
concept of what cancer was but were unable to define cancer in a biomedical or 
microbiological way.  
Unlike image, logic sacrifices form and replaces it with metaphor. Types of 
logic experiments done on RSV included the use of early filtration devices, 
quantification assays, and surveys concerning cancer occurrence. Logic relies on the 
accumulation of data, and on working with available knowledge and techniques to 
determine characteristics of the unknown. Research on RSV has shown that logic 
experiments were fundamental to the development of microbiology.  
However, later research on RSV also suggests that the delineation between 
image and logic experiments is not a clear divide. Though mainstream oncologists 
tended to study tumors by use of images, they were also interested in forms of logic 
experiments. For example, clinicians were also involved in quantifiable studies which 
looked at trends in carcinogenesis. Similarly, experimental pathologists extended a 
culture of quantification mechanisms and favored these over the course of early tumor 
virology research. However, it was the later development of electron microscopy 
imaging techniques that allowed laboratory researchers to confirm that viruses were 
 
 
48  
infectious organisms and not chemicals (Fawcett 740). In practice, researchers may 
utilize a combination of image and logic devices within one experiment. This has never 
been as evident as it is now. With the advent of imaging technology, it has become 
increasingly easier to analyze images in quantifiable ways.  
Image and logic traditions represent unique modes of knowledge transmission. 
However, as image and logic traditions relate to the existing scientific community, 
different groups of researches did not rely purely on one or the other technique. Rather, 
we can think about disparate image and logic traditions as being actors in trading zones. 
Each experimental tradition brings with it its own traditions, forms of knowledge 
retention, and utility. When researchers use a technique/technology they are engaging 
with the history and mode of knowledge acquisition inherent to the device. The contact 
between researcher and device can thus also be characterized as a form of trade. 
Conclusion 
Galison argues that the differences between scientific subsets adds to the 
strength and resilience of science. There is enough contact between different scientific 
traditions such that science at large and differing scientific groups can undergo large 
shifts in theory and experimentation without losing a sense of the overarching unity of 
science. This means that points of contact between these groups, or trading zones, are 
important for the overall strength of science. In my thesis I have shown the importance 
of interactions between scientific subsets to the history of RSV, that this history can be 
characterized by image and logic traditions, and that image and logic devices represent 
different modes of knowledge acquisition and retention.  
 
 
49  
Conclusion  
In my thesis I have explored the history of early experimentation on RSV and 
the development of image and logic traditions among scientists who were proponents 
and opponents of the extrinsic theory of cancer etiology. Cancer was first defined as a 
physical and biological condition. Experiments dealt broadly with who had it and who 
did not, how it appeared, and whether it was transplantable. Research on RSV, research 
on other tumor viruses, and the development of logic traditions within tumor virology 
eventually led to a molecular understanding of cancer etiology. In this conclusion I will 
elaborate upon the arguments I have made earlier in this thesis, discuss the importance 
of Image and Logic to RSV, and propose possible future directions for this research. 
Analyzing the interaction of distinct image and logic traditions is an important 
development for our current understanding of the history of RSV. The divide between 
extrinsic and intrinsic has already been explored by multiple historians, including Eva 
Becsei-Kilborn, Neeraja Sankaran, and Darwin Stapleton. However, what these 
histories lack is a detailed account of the relationship between scientific groups and the 
way that they look at data. By looking at the differences between the intrinsic and 
extrinsic groups along the lines of image and logic experimentation techniques, we 
begin to get at a deeper understanding of the fundamental difference in the way that 
clinicians and laboratory experimenters were collecting and communicating scientific 
data. 
In this thesis, the early history of experimentation on RSV has revealed inherent 
differences in the way that scientific data is organized in an image and logic system. 
Images work instantaneously. An image establishes information about cancer by 
 
 
50  
capturing one moment within cancer progression. For example, images are able to show 
whether or not a cancer has metastasized at a given moment in time. In contrast, logic 
experiments work through the accumulation of data and the establishment of a complex 
relationship of symbols and logical relationships. For example, in Rous’ 1911 
publication he conveyed the ability of filtrates to induce cancerous growths by looking 
at the frequency of cancerous tumors within chickens inoculated by filtrate. The 
difference between image and logic as modes of knowledge transmission indicate that 
clinicians and laboratory scientists developed not only a theoretical divide (extrinsic vs 
intrinsic) but were also organizing data in a fundamentally different way.  
While a distinct lineage of image and logic traditions emerged in the early part 
of the 20th century, the divide between the two is imperfect. Rous, for example, used 
both image and logic techniques. Many clinicians also engaged in forms of data 
accumulation or logic experiments like carcinogenesis studies. Furthermore, as John 
Ziman points out in his review of Image and Logic, image and logic traditions may not 
be as epistemologically distinct as Galison presents in Image and Logic (Ziman 292). 
For example, he argues that there may be multiple logical prepositions which are used 
to analyze an image. In RSV studies, the conclusion that RSV tumor segments were 
examples of sickle-cell sarcomas required the pre-establishment of what sickle-cell 
sarcomas were and then the identification of tumor segments as such. Furthermore, 
these images were used in order to show that filtrate inoculated tumors were “true” 
tumors which, one could argue, is the continuation of a logical argument.  
These discrepancies certainly complicate the epistemological distinction 
between image and logic. However, Galison’s discussion of image and logic as two 
 
 
51  
significantly different modes of knowledge transmission is ultimately useful to our 
understanding of the early history of RSV. In his review, Ziman concludes that in the 
history of physics, image and logic experiments produce essentially the same type of 
knowledge just in differing forms. I would argue that there is a fundamental difference 
between the wasy in which images and logic are used within early experimentation on 
RSV. There is a central difference between images of tumor segments, which rely on 
intuition and interpretation to produce meaning, and Rous’ charts, which build and lay 
out knowledge through the accumulation of multiple data points. The history of RSV 
does suggest that the image/logic divide may have been, in practice, a less distinct 
boundary than the image and logic traditions in Image and Logic. Furthermore, later 
developments in electron microscopy would largely integrate the image and logic 
traditions by allowing for the logical processing of images. However, ultimately images 
and logic did represent two fundamentally different modes of knowledge transmission 
that had different utilities to clinicians and experimental biologists within early 20th 
century research on RSV.  
Historically, I have discussed the importance of different image and logic 
traditions to the development of tumor virology and microbiology. Philosophically, I 
explore how images and logic represent different forms of knowledge transmission. In 
my thesis I have discussed how the types of experiments which scientists engaged in 
were related to the questions they asked, the type of data they used, and the theories 
they proposed. Instead of focusing simply on theoretical advancements, this type of 
historical analysis suggests that the relationship between scientists and experimentation 
techniques has important philosophical, historical, and theoretical implications.  
 
 
52  
There are many aspects of experimentation on RSV in the early 20th century still 
to be elucidated. I chose in this thesis to focus on the intrinsic interaction of scientific 
subgroups. Further analysis may link these intra-scientific interactions to society at 
large. Another direction for further research would be to continue our discussion of 
intercalated periodization. The differing rhythms of experimentation, theory, and 
technology has been a theme throughout the history of RSV. However, there is room to 
delve further into analyzing the benefits and characteristics of these differing rhythms. 
Ultimately, I hope to have shown that by understanding how the image and logic 
framework relates to the extrinsic/intrinsic divide, we gain an understanding about 
differences in the way in which differing scientific groups were collecting and 
communicating scientific data. While Image and Logic has been discussed in physics 
and economics, it has not often been applied to a biology. In this thesis I hope to have 
provided an argument for the utility of Galison’s philosophical framework to a 
biological history of scientific change, and to provide a baseline for further research on 
Image and Logic in biology.  
 
 
 
 
53  
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