The Wistar Rat as a Right Choice:

Establishing Mammalian Standards and

the Ideal of a Standardized Mammal*

BONNIE TOCHER CLAUSE

The Wistar Institute

3601 Spruce Street
Philadelphia, Pennsylvania 19104

In 1909 neuroanatomist Henry H. Donaldson wrote a beautifully

succinct testament to the "rightness" of the rat as a laboratory
animal:

As we have progressed with our studies on this animal, it has

become increasingly evident that the choice was a fortunate one,
as the albino rat is easy to keep, breeds freely, bears young that
are both numerous and immature, and is also responsive to
changes in its environment as well as being easily trained. It
would be hard to find another animal that combined so many
virtues in so compact and pleasing a form.1

Nearly fifty years later, referring to the descendants of Donaldson's

rats as the "famous colony of albino rats at The Wistar Institute
in Philadelphia," Curt Richter echoed Donaldson's tribute. Claiming
half a century of behavioral and neurological research using "many
different animals such as cats, dogs, monkeys, sloths, rabbits,
beavers, porcupines, honey bears, alligators, and others," Richter
wrote:

If someone were to give me the power to create an animal most

useful for all types of studies on problems concerned directly

* Based on a paper presented at the meeting of the International Society for

the History, Philosophy and Social Studies of Biology, Session on "The Right
Organism for the Job," Northwestern University, July 14, 1991.
1. Henry H. Donaldson, "An Outline of Studies on the Growth of the Nervous
System in Progress at The Wistar Institute of Anatomy and Biology," in Milton
J. Greenman, "Preliminary Statement to the Board of Managers of The Wistar
Institute", November 1909, p. 8, in Wistar Institute Library, Philadelphia, Pa.
(hereafter cited as WIL).

Journal of the History of Biology, vol. 26, no. 2 (Summer 1993), pp. 329-349.
9 1993 Kluwer Academic Publishers. Printed in the Netherlands.
330 BONNIE TOCHER CLAUSE

or indirectly with human welfare, I could not possibly improve

on the Norway rat. 2

Such accolades are not uncommon among the generations of

scientists who have used the rat as a laboratory workhorse, lending
credence to the choice of this animal as the "right" organism for
the job - or rather, the jobs, as rats continue to be used as exper-
imental models in a wide range of scientific and medical disciplines,
including neurology, nutrition studies, and behavioral psychology.
The long and well-documented use of rats in multiple fields of
research has resulted in the accumulation of a prodigious body of
data, providing another kind of user testimony to the value of
rodents, as well as validation for their efficacy as a model system
and a reference library of results upon which researchers can
continue to build. As Doris Zallen points out in her article in this
issue on Chlorella and other algae, and as Rob Kohler notes with
respect to Drosophila, 3 banks of data and the accumulated expe-
rience of investigators are strong factors driving the persistence
of use of Particular organisms for research, underscoring their
apparent "rightness" for the job.
In considering the case of the laboratory rat, the concept of
selecting the right organism for the job can be turned on its head
and extended to identifying the right job for the organism. Rats are,
after all, ubiquitous throughout the world and - until their use in
laboratories became well established - were universally regarded
as a useless scourge to humankind. Putting these animals to pro-
ductive use, however, was not simply a matter of rounding up the
vagrants from street and sewer and sending them off to utilitarian
employment in laboratories. Even the rats that Donaldson described
in 1909 had been domesticated by laboratory life and were gen-
erations removed from their wild progenitors, purchased from rat
catchers who "chose" them from back alleys and gutters. Purposeful
and systematic intervention was required to mold these feral
animals, unreliable and unpredictable, into biological entities that
could be counted on to consistently and invariably yield a pro-
ductive day's work. The vast difference between wild rats and
laboratory rats has been drawn by one rat historian using a telling
if somewhat hyperbolic analogy: "the laboratory rat is the

2. Curt P. Richter, "Experiences of a Reluctant Rat-Catcher: The Common

Norway Rat - Friend or Enemy?" Proc. Amer. Phil. Soc., 112 (1968), 403.
3. Doris T. Zallen, "The 'Light' Organism for the Job: Green Algae and
Photosynthesis Research," J. Hist. Biol., this issue; Robert E. Kohler, "Drosophila:
A Life in the Laboratory," ibid.
The Wistar Rat as a Right Choice 331

Hippocrates of ratdom; laboratory rats are to wild rats as Gandhi

is to Hitler - they are a separate rat race of Koches, or Pasteurs,
or Salks, or Madame Curies. ''4
The metamorphosis of the rat, from evil harbinger of pestilence
to hero of modern medicine, resulted from the work of many
researchers in various locales in the early part of this century.
Programs in rat breeding and husbandry were carried out at
numerous institutions, ranging from the Connecticut Agricultural
Experiment Station to the University of California, and resulted
in name-brand rats such as Osborne-Mendel, Long-Evans, and
Sprague-Dawley: It was at the Wistar Institute in Philadelphia,
however, that the concept of the rat as an instrument for scien-
tific research was most clearly articulated and that the engineering
of a superior animal was most vigorously promoted as an objec-
tive of the institution's scientific program.
The purposeful transformation of rats to create "standardized"
laboratory rats was undertaken at the Wistar Institute in Philadelphia
as a way of serving the needs of science while promoting the
goals of a fledgling scientific institution. The famous Wistar Rats
were bred and distributed by the Institute from 1906 through the
1940s. At one time in the not-too-distant past, "Wistar" was
synonymous with quality and dependability; researchers who
purchased Wistars were assured that they would be working with
the quintessential brand of rodents. In 1942 - some forty-six years
before the first patent was granted for a genetically engineered
laboratory animal - the Wistar Institute took steps to protect its
commercial rights in Wistar Rats and to limit the use of the Wistar
name to rats produced by the Institute. The name WISTARAT was
trademarked and was subsequently printed on labels attached to the
boxes in which the rats were shipped. 6 The Institute invoked its pro-
prietary rights and defended the exclusivity of its product on several
occasions, as in 1944, when Albino Farms was constrained to dis-

4. Robert Hendrickson, More Cunning than Man: A Social History of Rats and
Men (New York: Dorset Press, 1988), p. 211.
5. For a comprehensive overview of the development of the major strains of
laboratory rats, see J. Russell Lindsey, "Historical Foundations," in The Laboratory
Rat, Vol. I, Biology and Diseases, ed. Henry J. Baker, J. Russell Lindsey, and Steven
H. Weisbroth (New York: Academic Press, 1979), pp. 1-36. Lindsey's thorough,
well-researched, and enthusiastic survey of this aspect of twentieth-century
American science, while known to the scientific community, deserves to be more
widely read by historians of science as a synthesis of an underexplored area of great
interest.
6. Trade-Mark 396,978, registered August 11, 1942, with the United States
Patent Office.
332 BONNIE TOCHER CLAUSE

continue the use of the words "Wistar Strain" in its advertising. 7

"Wistar" is still synonymous with uniform quality in rats, and the
name is still used today, although the Wistar Institute sold the last
of its breeding stock and the rights to the name in the 1960s. The
Wistars survive in the bloodlines; it is estimated that more than half
of the present strains of rats used in laboratories today trace their
heritage to Wistar ancestors. 8
The story of how these famous rats came to be, and of how
and why their germline and repute have survived, and why their
market share surpassed that of the competition, is the story of the
people who grew them and the institutional context that nurtured
their growth. The Wistar Rat was the product of three different
scientific agendas; its promotion and survival as the preeminent
rat - both in reputation and in fact - was a function of institu-
tional mission and the goals of the Wistar Institute's director, who
set out to resurrect a small, independent institution and to insure
its survival in a time of change in the biological sciences. In this
sense the "job" of the Wistar Rat went far beyond its use as an
experimental animal, for it served as a vehicle for institutional
advancement as well as for the realization of three distinctive
visions of scientific progress. Only a broad outline of this story
is presented here, with the caveat that this condensed version is a
gloss, 9 especially in describing the Wistar Rat(s) as though they
were a single entity. Contrary to the popular epithet, "the" Wistar
Rats comprised a number of strains of Rattus norvegicus, including
several inbred and numerous outbred, or "random bred," strains.
The classic Wistar albino, the most widely used of the strains,
was supplemented by brown Norways and other varieties, including
some mutant strains. For the purposes of this paper, however, Wistar
Rats are described collectively, as the systematically bred com-
modities produced at the Wistar Institute, and some emphasis is
given to the inbred albinos as the prototypical standardized animal.
I will begin with a brief institutional biography, trace the research
agendas of the three main players - director Milton J. Greenman,
neurologist Henry H. Donaldson, and geneticist Helen Dean King
- and return to the unique institutional environment that provided
the requisite nurturance for a preeminent colony of small rodents.

7. Minutes of the Board of Managers of The Wistar Institute, April 24, 1944,
WIL.
8. Lindsey, "Historical Foundations" (above, n. 5), p. 30. Also see Michael
F. W. Festing, Inbred Strains in Biomedical Research (New York: Oxford
University Press, 1979).
9. A full account of the Wistar Institute rats and their creators, 1905-1955,
is in preparation by this author.
The Wistar Rat as a Right Choice 333

THE WISTAR INSTITUTE

The name "Wistar" derives from the Wistar family, the most
famous of whom was the colonial glassmaker's namesake and
grandson, Caspar Wistar, M.D., who held the chair of anatomy at
the University of Pennsylvania from 1808 until his death in 1818.
In 1892 Dr, Wistar's great-nephew, General Isaac Wistar, founded
the Wistar Institute to house the museum of anatomical and
pathological specimens and models initiated by the illustrious
physician in 1808 and augmented by his successors at Penn,
including William Horner and Joseph Leidy. 1~ Against this auspi-
cious background, the Wistar Institute was also given the broad
mission of serving the purpose of "seekers after new and original
knowledge." This open-ended mission statement - in conjunction
with the institution's original legal name, The Wistar Institute of
Anatomy a n d B i o l o g y - has been interpreted by the Institute as
giving it the status of the first independent biomedical research
institution in the United States. 11 Nevertheless, during the first
decade of its existence under the directorship of Horace Jayne,
the Institute remained tied to the nineteenth-century traditions of
descriptive anatomy and comparative morphology.
By 1905, nearly thirteen years after its founding, the Wistar
Institute had not gone far beyond realization of the part of its
mission that called for the maintenance and augmentation of the
Wistar Museum. In that year, apparently because General Wistar
was dissatisfied with the performance of director Horace Jayne,
Milton J. Greenman was named to the directorship. Greenman's
education and early career incorporated a range of experiences,
sowing the seeds for the broad view of the scientific enterprise
that later became manifest in his direction of the Institute.
Greenman was a graduate of Penn's school of biology (1889) as
well as its medical school (1892); before taking the job as Jayne's

10. Simon Baatz, "The Wistar Legacy: Medical Science in Philadelphia,

1796-1905," unpublishedMS, WIL, traces the antecedentsand history of the Wistar
Institute from the late eighteenth century through its first decade.
11. Jeffrey Broscoe, "Anatomy and Ambition: The Evolution of a Research
Institute," Trans. Stud. ColL Phys. Philadelphia, 5th ser., 13 (1990), 1-28, focuses
on the founding and early years of the Wistar Institute, with particular attention
to the question of General Wistar's intentions and motivations vis-a-vis the
Institute's purpose. With its ties to medicine, museums, and experimental science,
the Wistar Institute was an interesting and somewhat enigmatic hybrid in the era
when biology was being defined. Cf. Jane Maienschien, ed., Defining Biology:
Lectures from the 1890s (Cambridge, Mass.: Harvard University Press, 1986),
pp. xi-xiii, 3-50, 51-56; Philip J. Pauly, "The Appearance of Academic Biology
in Late Nineteenth-Century America," J. Hist. Biol., 17 (1984), 369-397.
334 BONNIE TOCHER CLAUSE

assistant in 1894 he had been an instructor in biology at Penn,

and in 1888 he had worked at the U.S. Fish C o m m i s s i o n ' s
Department of Scientific Inquiry at Woods Hole. t2 As assistant
director at the Wistar Institute, Greenman was primarily engaged
in museum work, showing great ingenuity as an inventor, shrewd-
ness and an entrepreneurial spirit as manager of Institute properties
and investments, and - as soon became apparent - an understanding
of current trends in science and industry and the ability to imple-
ment his ideas. During his eleven years as J a y n e ' s assistant,
Greenman must have been holding ambition in check; upon being
named director in 1905, he wasted no time in charting new direc-
tions for the Institute and set about gathering the expertise and
human resources to further his plans. Invoking rhetoric reminis-
cent of the 1902 founding documents of the Carnegie Institution
of Washington, ~3 Greenman identified a new mission for the Wistar
Institute: to serve as "the central anatomical institute of this country.
The clearing house of anatomy, so to speak"; he urged coopera-
tion and cautioned against isolation as one of the "chief dangers
which may befall an independent institution. ''14 Many years later,
he reiterated his early vision for the Institute, as rending "national
as well as local s e r v i c e . . , to advance anatomical and biological
science. ''~5 To assist in carrying out this objective Greenman assem-
bled a group of prominent anatomists, consisting of the cream of
James M c K e e n Cattell's starred anatomists and zoologists. 16
Meeting in Philadelphia in April 1905, this group declared "the
principal object of The Wistar Institute to be research," and
recommended Henry H. Donaldson as the chief scientist to carry
out this goal. 17

12. Greenman's association with Woods Hole continued throughout his life
through his affiliation with the Marine Biological Laboratory. The environment
he encountered at the Fish Commission station in 1888 - significant as the founding
year of the MBL - is described by Dean C. Allard, "The Fish Commission
Laboratory and Its Influence on the Founding of the Marine Biological Laboratory,"
J. Hist. Biol., 23 (1990), 251-270.
13. See Howard S. Miller, Dollars for Research: Science and Its Patrons in
Nineteenth-Century America (Seattle and London: University of Washington Press,
1970), pp. 172-173.
14. Milton J. Greenman, "Report to the Board of Managers of the Wistar
Institute, 1905" unpublished report, WIL.
15. Milton J. Greenman, "The Wistar Institute of Anatomy and Biology and
Its Advisory Board," Bull. Wistar Inst., 6 (1925), 33.
16. James McKeen Cattell, ed., American Men of Science (New York: Science
Press, 1906) (and subsequent editions).
17. Minutes of the Board of Managers of The Wistar Institute, April 1905,
WIL.
The Wistar Rat as a Right Choice 335

THE RESEARCHERS

The arrival of Henry Donaldson in Philadelphia was the first step

in implementing Greenman's vision of a new era for the Wistar
Institute. Donaldson arrived with several significant kinds of
baggage, both metaphorical and material: a career history that
was classic for the times; well-established relationships among
the "club" of his scientific peers; a well-formulated research
agenda, ripe for realization; and research material in the form of
several breeding pairs of albino rats. Donaldson had been
educated at Yale and Johns Hopkins; he was well grounded in
both physiology and morphology, having trained with Russell
Chittenden at the Sheffield Scientific School and both H. Newell
Martin and William Keith Brooks at Hopkins. He had been a
member of the faculty of Clark University and then of the
University of Chicago. He identified himself as a neurologist and
had originally focused on the growth and development of the brain;
this work evolved into an endless - and seemingly fruitless -
lifelong attempt to correlate brain size and weight with intelligence.
In undertaking these investigations Donaldson became aware that
there were no data on the growth of the brain or the nervous system
from birth to maturity, for humans or for any other species. TM The
study of the growth of the nervous system over time, and the effects
of environmental conditions on neurological development and the
brain, thus became the focal point of Donaldson's work from that
point on.
At Chicago Donaldson had worked increasingly with fresh (i.e.,
not preserved) and living experimental material, refining his work
to include cytological studies of the size and weight of nerve cells
and fibers, first in frogs and then in r a t s . 19 He later attributed the
choice of the rat to a

passing remark by my colleague, [the Swiss neuropathologist]

Dr. Adolf Meyer, to the effect that the smaller the kind of brain
with which one worked, the easier it was to progress rapidly.

18. Edwin G. Conklin, "Henry Herbert Donaldson, 1857-1938," Biog. Mem.

Nat. Acad. Sci., 20 (1938), 231.
19. The environment in which Donaldson worked at Chicago has been
described in depth by Philip J. Pauly, Controlling Life: Jacques Loeb and the
Engineering Ideal in Biology (New York: Oxford University Press, 1987). Also see
Jane Maienschein, "Whimaan at Chicago: Establishing a Chicago Style of Biology?"
in The American Development of Biology, ed. Ronald Rainger, Keith R. Benson,
and Jane Maienschein (Philadelphia: University of Pennsylvania Press, 1988), pp.
151-182.
336 BONNIE TOCHER CLAUSE

Following this suggestion, we began to grow rats in the

laboratory.:~

Some twenty years later, Donaldson gave a more structured account

of Meyer's influence in his original selection of the rat:

Dr. Adolf Meyer in 1893 gave a course on the anatomy of the

nervous system in the neurological laboratory at Chicago. For
this course he used the albino rat, and thus this animal was
brought to our attention. The surviving rats were left in the
laboratory and further used, so that gradually those working with
them grew to appreciate the fact that for many purposes, and
especially for the study of growth changes in the nervous system,
the albino rat was an ideal animalflI

With Donaldson and the rats on board, Greenman's ambitions

for the Wistar Institute began to flower. Under his direction the
Institute came to concentrate its services to the larger scientific
community in two areas: the publication of journals, beginning with
the assumption from C. O. Whitman of the semidefunct Journal
of Morphology in 1907; and the establishment of the animal colony
and the mass production and distribution of rats bred for use in
the laboratory.
Greenman mentioned the animal colony for the first time in his
Director's Report for 1907, writing that it had been "successfully
maintained" and was capable of supplying "fresh material" for
the Institute's work and for that of unspecified others. = By 1908,
a number of concepts had come together for Greenman: he had
developed an appreciation of Henry Donaldson's research problem
of neurological growth and the conditions that influence it; he had
come to understand the importance of using one species as the
object of that study; and he recognized the movement within the
scientific community "from the field of dead anatomy into a field

20. Donaldson, "Outline 0f Studies" (above, n. 1), p. 6. The probable European

origin of the rats used by Adolf Meyer has been traced and described by Lindsey,
"Historical Foundations" (above, n. 5).
21. Henry H. Donaldson, "Research at The Wistar Institute, 1905-1925," Bull.
Wistar Inst., 6 (1925), 44.
22. Milton J. Greenman, Director's Report for 1907, p. 4, WIL. Adele E. Clarke
has analyzed the development of the "new infrastructure" required to meet the
increased demand for live and fresh materials during this period in the history of
the life sciences: "Research Materials and Reproductive Science in the United
States, 1910-1940," in Physiology in the American Context, 1850-1940, ed. Gerald
L. Geison (Bethesda, Md.: American Physiological Society, 1987), pp. 323-350.
The Wistar Rat as a Right Choice 337

of living anatomical structures," and from working with "any kind

of material that came to hand" to employing "an animal of a given
t y p e . . , of known qualities and quantities." He extolled the value
of the "White Rat" for its "convenient size and intellectual quali-
ties, together with its ability to breed rapidly (under favorable
conditions)." Most important, he had also begun to associate the
need for research animals with the Institute's mission of advancing
anatomical science:

Anatomical studies are rapidly coming to a condition of math-

ematical accuracy and just as the chemist, to make a proper
analysis, must purify and standardize his reagents, so must the
anatomist, to make a complete qualitative and quantitative
solution of anatomical structure, breed a research animal of
known qualities and purity of strain with which to make his
determinations, z3

Also apparent in the 1908 Director's Report are the glimmerings

of Greenman's realization of the management possibilities of the
rat colony. He had encountered Frederick W. Taylor's system and
principles of time economy through a reading of his manuscript
on "Shop Management," which Greenman found to be "applic-
able to an Anatomical Institute as well as to a machine shop. ''24
He vowed to introduce such methods to the Institute for greater
efficiency of operation. Taylor's system had fallen upon fertile
soil in Milton Greenman, for whom such an approach to manage-
ment and administration, maximizing the utilization of scarce
financial and human resources, seemed to be second nature. He
designated the Junior Associate in Anatomy, J. M. Stotsenburg,
to do double duty in assuming charge of the animal colony, and
he had his eye on the city's Police Station, which occupied a plot
of land adjacent to the Institute proper, as ideal for a vivariumY
While the rat supply during 1908 had been maintained largely
through purchases, Greenman's observations had indicated the

23. Milton J. Greenman, Director's Report for 1908, pp. 8, 12, WIL.
24. Ibid., p. 2.
25. Greenman's use of the word "vivarium," as well as other rhetoric
surrounding his descriptions of the animal colony, are reminiscent of Charles O.
Whitman's impassioned pleas for improved facilities for laboratory animals.
Greenman knew Whitman through the MBL and also through Whitman's close
association with Donaldson. See Charles O. Whitman, "The Hull Zoological
Laboratory," in The President's Report [of the University of Chicago] (Chicago:
University of Chicago Press, 1903), p. 435; and see Maienschein, "Whitman"
(above, n. 19).
338 BONNIE TOCHER CLAUSE

potential for breeding under controlled conditions, and he had

already introduced to the colony instruments for regulating tem-
perature, devices to improve cage sanitation, and an outdoor area
with a dirt floor, exposed to natural light, as a kind of exercise
yard for the resident rats. Greenman had also identified a
scientific problem for himself: "As many other institutions are
adopting the white rat as its research type, we feel that the solution
of the problem of breeding this animal in great numbers is a matter
of prime importance. ''26
Greenman's conceptualization of the animal colony and the
breeding of the white rat as problems to be solved - including his
definition of the desirable parameters of quantity and quality, to
be attained through controlled breeding and environmental condi-
tions - was probably the single most important factor that led to
the development of the Wistar Rats during the next ten years.
Meanwhile, Donaldson embarked on his collection of neurolog-
ical data for the albino rat, providing a constant in-house market
for the fruits of Greenman's colony, and in 1909 a third element
was added to the rat equation, in the person of Helen Dean King.
Helen Dean King had earned her doctorate in zoology from Bryn
Mawr, studying morphology under Thomas Hunt Morgan. By 1906
she had published four papers based on work concerned with inver-
tebrate embryology and development. From 1906 to 1908 she
worked with Edwin G. Conklin at the University of Pennsylvania,
pursuing studies on sex determination in the common American
toad. On February 1, 1909, King was elected to the Wistar staff
as Assistant in Anatomy. Her work during the first years included
certain laboratory services, such as the preparation of histological
sections,z7 In 1911, while reporting on her "interesting and impor-
tant results" in experiments on sex determination in toads,
Greenman noted that "Doctor King came to the Institute as a
technician with the privilege of devoting a portion of her time to
research. ''2s Despite this limited view of her role, by 1910 King had
been subsumed as part of Donaldson's small research team, engaged
in studies of aspects of neurological growth in the albino rat. King's
summary of her own work for 1910 was divided into two sections,

26. Greenman, Director's Report for 1908, p. 12.

27. Milton J. Greenman, Director's Report for 1909, p. 4, WIL. The "service"
work that King did during her first few years at Wistar, as well as some of the
miscellaneous tasks assigned to her throughout her long career, fit well the model
of "women's work in science" described by Margaret Rossiter, Women Scientists
in America: Struggles and Strategies to 1940 (Baltimore and London: Johns
Hopkins University Press, 1982).
28. Milton J. Greenman, Director's Report for 1911, p. 9, WIL.
The Wistar Rat as a Right Choice 339

"work in progress" and "technical work." Her work in progress

included a study on the effects of inbreeding on the sex ratio of
the albino rat; the rats produced in the course of the last experi-
ment, she noted, were also being used by Shinkishi Hatai and
Donaldson in their study of the effects of inbreeding on the central
nervous system. 29 In this experiment, then, the rat played an
interface role between the different research interests of King and
Donaldson.
By 1909 the disparate agendas of Greenman, Donaldson, and
King had already coalesced toward a product that would serve an
institutional goal. Some nine years later, in the introduction to the
first of her four Studies on Inbreeding, King said that in initiating
her inbreeding experiments she was "taking advantage of the
opportunity which the animal colony at The Wistar Institute
afforded. ''3~ Breeding would produce more material for Donaldson's
experiments, by now focused almost exclusively on the rat, and
inbreeding would be yet another variable for Donaldson to analyze
in his exhaustive study of the effects of inherited and environmental
conditions on the growth of the nervous system. Greenman's
promotion of the ideals of cooperation and efficiency would be
exemplified by the use of one rat for two experimental purposes.
If there was real ingenuity in the initial formulation of this
experimental set, however, it was probably King's. As the female
junior staff member who was expected to carry out routine work
for Donaldson and others, designing her own experiments so as
to capitalize on these technical services would have been an appro-
priate adaptation. In addition, the availability of the albino rat at
Wistar opened up the field of mammalian genetics to King, at a
time when geneticists were diversifying from the study of embry-
ology in amphibians and marine invertebrates and moving toward
animal models that offered the opportunity to study the more
complex notions of blended inheritance and to sort out the inter-
play between heredity and environment. All of these factors, then,
favored King's immersion in the inbreeding experiments that
furthered her own research ends while providing material for
Donaldson and others, incidentally adding to the distinctive quality
of the growing colony of rats at the Wistar Institute.
Henry Donaldson, meanwhile, had continued his single-minded
pursuit of a comprehensive set of quantitative parameters of

29. Milton J. Greenman, Director's Report for 1910, p. 13, WIL.

30. Helen Dean King, Studies on Inbreeding (Philadelphia: Wistar Institute
of Anatomyand Biology, 1919; reprinted from J. Exp. Biol., 25 [1918]; 27 [1918];
29 [1919]), p. 3.
340 BONNIE TOCHER CLAUSE

neurological growth and development, under all conceivable

circumstances of variation. His research report for 1909 begins
on the didactic note characteristic of stage-setting for momentous
undertakings: "By the formulation of a problem one establishes a
basis for arranging in a certain order, and approaching in a definite
way, the phenomena that are to be investigated. In the present
instance the problem of growth is the one which has been selected
for study, and it is readily seen that there is not a character or
function of living organisms which may not be considered in its
relation to the growth process. ''31 In recognizing the universal
applicability of characters and functions of growth, Donaldson set
out what was essentially a limitless task, one that occupied him and
scores of assistants and students over the next thirty years. In
addition to this boundless research protocol, he undertook the
equally expansive "ultimate object" of doing no less than under-
standing and improving the human nervous system. Donaldson
had also determined another characteristic essential to his ultimate
goal: that the growth curve for the rat was comparable to that for
man, which, he claimed, would allow direct extrapolation of
experimentation and observation from that species to humans.
As well as establishing growth parameters for the albino rat over
time, Donaldson sought to compare the domesticated albino with
its wild progenitor, the grey Norway rat, especially to elucidate
the reasons for the lesser weight of the nervous system of the albino.
He broke the "idea of domestication" down into three factors: the
absence of the struggle for existence; interbreeding; and lack of
exercise. In collaboration with Shinkishi Hatai, he then embarked
on a series of breeding experiments to show whether central nervous
system weight was inherited and related to albinism as a physio-
logical condition, or acquired as the result of the external conditions
associated with domestication. Albinos were crossed with greys
to examine the effects of blended inheritance in extracted off-
spring of both varieties, and, with the purposeful introduction of
new stock to imitate natural selection, to demonstrate the effects
of interbreeding. Experiments would also use wheel cages to
observe the effect of lifetime exercise (Donaldson noted that rats
"often voluntarily run five to ten miles a night in such cages"). 3z
In addition to quantifying gross parameters of growth and
physiological changes within the central nervous system over the
life span of the rat, Donaldson's program included studies of the
size and number of neurons and dendrites and of chemical changes

31. Henry H. Donaldson in Greenman, Director's Report for 1909, p. 8.

32. Ibid.
The Wistar Rat as a Right Choice 341

associated with the formation of myelin. Finally, he was also

interested in determining whether "ability," as measured by
susceptibility of the rat to training, was correlated with weight of
the nervous system, and thus whether "clever" and "stupid" strains
could be produced through selective breeding. In all aspects of
this work Donaldson collaborated most closely with Shinkishi
Hatai, who not only carried out his own experiments but also
developed a series of biometrical methods to aid both Donaldson's
and King's researches. 33Donaldson's research program was further
implemented and augmented by other members of the small Wistar
staff (such as J. M. Stotsenburg, who studied the effects of spaying
and castration on growth), and by outside investigators (such as
William Addison, who studied the Purkinje cells) who worked along
lines that paralleled and complemented Donaldson's investigations,
adding to the volume of data - often published in the Wistar Press
journals - that were accumulated about the rat in general and the
laboratory-reared albino in particular.

THE GOAL OF STANDARDIZATION

Greenman the modern manager evidenced a new theme in 1910:

standardization, the byword for his report in that year. The Institute
should establish standards of all kinds, he maintained, beginning
with "standards in anatomical work" and extending even to the
establishment of a system of standard magnifications for all illus-
trations to be published in the Wistar journals. In typical fashion,
Greenman used as a reference point a technological model other-
wise unassociated with experimental biology: "the standard screw
threads suggested by William Sellers many years ago and adopted
by all American mechanics. Such standards result in immense
economies in science as well as in c o m m e r c e . ''34
Unlikely as the association to rats may seem, Greenman's
referents here are both clear and relevant. The Sellers screw thread,
also known as the United States Standard Thread System, was
developed at the Franklin Institute in Philadelphia in 1864, to
standardize American railroad lines and equipment. Screw threads
remained one of the focal points of the work of the United States
Bureau of Standards throughout the first decades of the twentieth
century, as critical to the principles of interchangeable parts, mass
production, and international standardization of industry. It is

33. Shinkishi Hatai, "A Mathematical Treatment of Some Biological

Problems," Biol. Bull., 18 (1910), 126-130.
34. Greenman, Director's Report for 1910, p. 7.
342 BONNIE TOCHER CLAUSE

probable that Greenman was not only familiar with the Bureau's
work but also influenced by it, both in his perception of the
importance of standards and in his awareness of their implemen-
tation in the chemical and physical sciences. Beginning in 1905,
in cooperation with the American Chemical Society, the Bureau
Of Standards was engaged in formulating "standards of purity for
chemical reagents and standard methods of technical analysis, and
[in carrying out] the physical and chemical examination of a number
of substances with the view of determining standards and standard
specifications to be employed in the purchase of government
supplies.'35
Greenman's interest in standards and standardization was
congruent with his interest in the work of Frederick W. Taylor -
another Philadelphian, who was also inspired by William Sellers.
In 1908 Greenman had read Taylor's Shop Management, in which
Taylor wrote that "the economy to be gained through the adoption
of uniform standards is hardly realized at all by the managers of
this country. ''36 Taylor said that "many of the elements [of man-
agement] that are now believed to be outside the field of exact
knowledge will soon be standardized, tabulated, accepted and used,
as are now many of the elements of engineering." These elements
included "standard conditions" in the workplace: "the adoption and
maintenance of standard tools, fixtures, and appliances down to
the smallest item throughout the works and office, as well as the
adoption of standard methods of doing all operations which are
repeated, is a matter of importance, so that under similar conditions
the same appliances and methods shall be used throughout the
plant. ''37
The influence of Taylor's principles was evident in Greenman's
conceptualization and development of the Wistar rat colony. The
management of the animal colony to produce abundant material for
Donaldson's research program had become a major focus of
Greenman's administration as early as 1909. In that year he noted
that the colony had been placed "upon a scientific basis" - clearly

35. Gustavus A. Weber, The Bureau of Standards: Its History, Activities, and
Organization (Baltimore: Johns Hopkins Press, 1925), p. 43.
36. Frederick Winslow Taylor, Scientific Management: Comprising Shop
Management, The Principles of Scientific Management, Testimony before the
Special House Committee [paginated separately]. (New York: Harper, 1947), Shop
Management, p. 124; Greenman, Director's Report for 1908, p. 2. Shop
Management was first published in 1903, under the auspices of the American
Society of Mechanical Engineers. Re "Taylorism" also see Thomas P. Hughes,
American Genesis (New York: Viking, 1989), pp. 188 ff.
37. Taylor, Shop Management, p. 116.
The Wistar Rat as a Right Choice 343

echoing Taylor's rhetoric - and as a result had succeeded in

enabling the extension of the research work and facilitating its rapid
completion. 38 Wistar's use of the albino rat as an experimental
animal was being emulated by other laboratories, who were securing
their breeding stock from the Institute's colony, spurring Green-
man's interest in the efficient production of large numbers of
quality-controlled animals.

THE PRODUCTION AND PROMOTION OF RATS

By 1912, Greenman was thoroughly convinced that the rat

colony was fundamental to the successful work of the Institute. The
rats had had their most prolific year, producing 6,431 offspring. The
total number of rats in the colony in 1913 soared to 11,000, with
8,000 used within the Institute itself. As important, especially to
Greenman's original goal of establishing the Wistar Institute as a
central anatomical institute providing services to the national
community, was the growing number of rats that were sent to
other institutions: in 1912, a total of 2,135 animals were thus dis-
tributed, rising to 3,000 in 1913. Greenman reported that
"cooperative work with a number of other laboratories [was] being
actively pursued . . . . brought about by the extensive work which
has been done upon the Albino rat by Prof. Donaldson and his
associates in establishing norms and by the maintenance of a large
colony of these animals at the Institute. ''39
By early 1915 the rat colony had become a well-established
fixture at the Wistar Institute. All the conditions that had led to
its establishment were operative in assuring its growth and
perpetuation: Donaldson's requirements for experimental material,
focused almost exclusively on the rat; King's ongoing breeding
experiments, which both fed her own research objectives and
guaranteed the propagation of the species; and Greenman's inter-
ests in management and the provision of service to science, focused
increasingly on the rat colony. In addition, the Board of Managers
had reviewed the colony and authorized its continuation as a
legitimate and important function of the Institute, thus insuring that
funds for colony support would be allocated. Rats were being
distributed to an ever-widening network of other laboratories, as
the result of the linkages of the Wistar Institute and its three key
staff members to the greater scientific world. In the promotion of

38. Greenman, Director's Report for 1909, p. 11.

39. Milton J. Greenman, Director's Report for 1913, p. 3, WIL.
344 BONNIE TOCHER CLAUSE

the rat as a product, each of the three again served a separate and
yet complementary role.
The first edition of Henry Donaldson's book The Rat: Data
and Reference Tables for the Albino Rat and the Norway Rat was
published in 1915 as Memoir No. 6 of the Wistar Institute. The
volume is an exhaustive compilation of data drawn from the
biological, anatomical, and physiological observations made by
Donaldson and his colleagues over a ten-year period; the bibliog-
raphy lists more than a thousand items, all pertaining to the rat. 4~
The publication of this book, as a compilation of standards for
the growth and development of the rat, was central to the recog-
nition of the rat as the first "standardized" laboratory animal. Until
the work of Donaldson such baseline statistics had not been
compiled for any mammal, even for humans, and the data must have
been attractive to other experimental biologists who were using
living animals for controlled experiments. In the second edition
of his book (1924), Donaldson's long prologue is full of caveats
about the use of the reference tables: "As to the table values them-
selves, one hastens in the first instance to disclaim the suggestion
that they furnish standards of the same type as are to be had in
the physical sciences. In the very nature of the case such accuracy
and constancy is unattainable, for all animals at all times are in a
state of flux. ''41 Nevertheless, the value of the data, Donaldson
maintained, was in offering "base line values to which those of
the controls used in any investigation may be referred." In addition,
changes in the actual values (e.g., in whole body weight of albino
rats, which tended to increase in successive generations) were
obviated by the growth curves, which reflected a proportionality
that was maintained despite the changes in the real value of
individual parameters.
The publication of Donaldson's book served indirectly to
promote the Wistar Rats. As the publisher of five biological
journals, the Wistar Institute was able to advertise its own products
worldwide with virtually no additional expenditure of revenues.
Thus, while the rats themselves were not advertised, the book The
Rat was marketed in full-page advertisements at the back of the
Wistar journals, which by 1915 were being distributed to thousands
of scientists in laboratories throughout the world. In today's terms,
buying the book without the animals would have been analogous

40. H.H. Donaldson, The Rat (Philadelphia: Wistar Institute Press, 1915). The
second edition, published in 1924, contained 1300 additional titles in its bibliog-
raphy, as well as 150 pages of additional data.
41. Ibid., p. xi.
The Wistar Rat as a Right Choice 345

to buying the documentation without the software. Thus the exis-

tence of the reference tables and the promotion of the book served
to further the use of laboratory rats in investigation, and the use
of Wistar-bred rats in particular.
Donaldson also promoted the rat in a more indirect manner, as
an inveterate and indefatigable association member, meeting-goer,
socializer, spokesperson, and writer of scientific opinion pieces.
His name lent prestige to the Wistar Institute and was closely
associated with the rat; thus it is logical to assume that this
"celebrity endorsement" was yet another contributory factor in the
growing repute of the Wistar Rat.
A more direct link to research interests in the larger scientific
community - especially through mammalian geneticists such as
William E. Castle and Charles B. Davenport - was evident in the
inbreeding experiments of Helen Dean King, begun in 1909 and
published in four parts beginning in 1918. 42 In the mythology of
the Wistar Institute her work is still referred to as "painstaking"
- and that it was, as she followed her series of closely inbred rats
through tens of generations of brother-sister matings, continuously
selecting offspring for desirable characteristics. The results of
King's years of carefully controlled breeding experiments were
twofold. First, she showed definitively that inbreeding need not
be injurious; on the contrary, if individuals with desirable charac-
teristics were selected for breeding, the effect would be enhance-
ment of these traits - in the case of rats, increased size and weight,
vigor, and fertility. Second, she succeeded in producing a superior
strain of inbred albino rats - the rats that became the best known
of the Wistar strains because of their health, vigor, and other qual-
ities that made them desirable for laboratory experimentation. An
additional offshoot of King's breeding experiments was her
inadvertent discovery of some of the elements of nutrition and
environmental control that were conductive to the raising of better
rats, as reported by Greenman in the animal colony section of his
annual Director's Reports.

STANDARD ANIMALS

By 1915 the development of the Wistar albino rat as a "standard"

laboratory animal had traced a somewhat convoluted path, starting
from the concept born with Donaldson's striving for the accumu-
lation of statistical norms, or standards, of mammalian growth,
and his choice of the rat as the biometrical model. In combina-

42. King, Studies in Inbreeding (above, n. 30).

346 BONNIE TOCHER CLAUSE

don with Greenman's interest in technological and managerial stan-

dardization, based on the ideals of efficiency, economy, and
uniformity, Donaldson's rat standards were gradually transformed
into the idea of uniform, standard rats, or rats that would embody
statistical norms for growth and development and that could be
reproduced in quantity. Thus the Wistar albino was the result of
the conceptual cross of the ideal and the real - and sometimes the
two were confounded, even by the rat's principal developers.
Donaldson himself, while recognizing the variation inherent in
any living population and thus cautioning against the applicability
of his rat reference tables to individual animals, had nevertheless
written that the Institute "should be able to furnish perfect animals. 43
This trust toward uniformity and apparent perfection was realized
through King's breeding experiments; as a result of the process
of close inbreeding and continuous selection for desirable traits, the
gene pool was narrowed down so that the probability of "breeding
true," or achieving reproducible genetic uniformity, was maximized,
and the possibility of the appearance of undesirable or new traits
was minimized. King's inbred series of rats, which had reached
its twenty-second generation in 1915, was unique for experimental
biology at that time, and indeed can be thought of as the approx-
imate forerunner of the exact copies of living organisms produced
by cloning. Thus the Wistar Institute was able to produce rats of
known traits, both anatomic and genetic, biometrically quantifi-
able within a known range of variation and comparable to a set
of known growth curves. The inbred Wistar albinos, then, were
initially defined and promoted as "homogeneous," meaning that
they were thought to be predictably uniform in both measurable and
hidden traits.
As early as 1911 Greenman began to refer to the Wistar albinos
as "material of standard type," long before the means for produc-
tion of reliably uniform animals had been realized - indeed, before
the influences of nutrition and other environmental variables were
clearly understood. While Greenman always recognized the need
for controlled environmental conditions associated with particular
experiments, as it became possible to closely control the heredity
of the rats he became more interested in controlling the external
variables that affected their growth and development. And as the
rat became increasingly useful to investigators both within and
outside the Institute, Greenman's interest moved from the animal
colony as an essential part of a research institution to the unique

43. Henry H. Donaldson in Milton J. Greenman, Director's Report for 1913,

p. 6, WIL (emphasis added).
The Wistar Rat as a Right Choice 347

qualities of the Wistar rat colony as a whole and the potential for
its improvement through management as a controlled environment
- so the rats could be maintained at a "constant physical standard,"
as he put it. Thus the idea was to produce Donaldson's idealized
"perfect animals" in a setting that was characterized by "perfect
conditions." Although it took a number of years for Greenman to
recognize the difficulty of achieving this objective for a commu-
nity o f small rodents, once he had identified the scope of what
was required to control the range of external variables that affect
the well-being of rats, the colony became a major focus of his
career. For Greenman the quintessential administrator, after years
of running a small institution with a limited cadre of independent
scientists, the rat colony with its thousands of caged and depen-
dent rodents must have represented a brave new frontier for the
application of management science.
In 1923 Greenman and Louise Duhring, who was named curator
of the animal colony in 1921, published a slim volume that gives
the remarkable details of what they had achieved in their rat colony.
The book, Breeding and Care of the Albino Rat, represents an
apogee of Greenman's career. Although it contains only 120 pages,
it is the major publication of his lifetime, and it evidences the
ways in which all of Greenman's attributes - as scientist, admin-
istrator, manager, problem-solver, technologist, and inventor - came
together around the management of the rat colony. This detailed
guide to the husbandry of albino rats for research purpose -
including, for example, exacting specifications for cages and
a foldout plan for their construction - is clearly the result of
collaboration between Duhring and others, who spent their working
days in the colony and were intimately familiar with the habits
and preferences of their small animal charges, and Greenman, who
designed the apparatus to solve a particular problem, or located a
piece of equipment that would work for a specialized purpose.
The fruit of this collaboration is a compendium that shows concern
for the animals' comfort and even their feelings, coupled with
Greenman's technical ingenuity applied to equipment design to
achieve an optimal environment with economy and efficiency.
Greenman and his colleagues had realized that living organ-
isms were not perfect, like chemicals, nor perfectly standardizable
organisms:

It was assumed in the beginning of our experiments (results to

be published elsewhere) 44 on the production of albino rats for
44. Unfortunately, the results were never published, at least not directly by
Greenman.
348 BONNIE TOCHER CLAUSE

research purposes that, beginning with a clean, healthy stock and

a uniform diet with uniform environmental conditions, we could
produce a standard or uniform animal within accepted limits
of variation . . . . The results were not what we had expected
[e]ven with a diet as well balanced and uniform as may be
devised, with environmental conditions as uniform as may be
secured . . . . and many other conditions of a subtle nature which
influence the growing mammal. All these, together with the
variable and undeterminable state or conditions of the albino
rat itself in its reaction to food and to external influences, result
in a constantly changing organism.45

Greenman and Duhring's book was prepared at the request of

scientists who were using the Wistar Rats or their descendants in
other research facilities far from Philadelphia. By the time the book
was updated, in 1931, the Wistar Rats were being used in labora-
tories around the world, having been sent as far afield as China
and Japan. In this second edition, Greenman included reference
tables and growth charts, using weighings from 1928 to update
the quantitative data for the experimental colony, furthering
Donaldson's goal of providing a set of comparative standards for
investigators in other laboratories.

CONCLUSION

In summary, the creation and maintenance of the Wistar Rats

as standardized animals can be attributed to the breeding work of
Helen Dean King, coupled with the management and husbandry
methods of Milton Greenman and Louise Duhring, and with
supporting documentation provided by Henry Donaldson. The
widespread use of the Wistar Rats, however, is a function of the
ingenuity of Milton Greenman who saw in them a way for a small
institution to provide service to science. Greenman's rhetoric, as
captured in his Director's Reports, prepared annually from 1905
until his death in 1937, shows that he was unusually sensitive to
his times and to the economics of science and of society. In the
era when biology was being defined, he recognized in the rat the
potential to be a living analog to the pure chemicals that legitimated
experimental science. From management literature he extracted
the ideals of uniformity of product, standards of quality, and

45. Milton J. Greenman and F. Louise Duhring, Breeding and Care of the
Albino Rat for Research Purposes, 2nd ed. (Philadelphia: Wistar Institute of
Anatomy and Biology, 1931), p. 45.
The Wistar Rat as a Right Choice 349

efficiency of production, applying them to scientific practice to

generate an animal model that thrives as standard equipment in
laboratories throughout the world today.
I will close with a quote from Frederick W. Taylor that is a
cogent statement of the contribution to science and scientific
progress made by standardized tools and their creators. Equating
the surgeon and the workman, Taylor wrote:

[He is given] the finest implements, each one of which has

been the subject of special study and development . . . [and]
the very best knowledge of his predecessors; and, provided with
standard implements and methods which represent the best
knowledge of the world up to date, he is able to use his own
originality and ingenuity to make real additions to the world's
knowledge, instead of reinventing things which a r e old. 46

Standardized tools, whether surgeons' implements or laboratory-

bred rats, are one of the vehicles for carrying scientific knowledge
forward from generation to generation. In this sense, Greenman's
Wistar Rats have done their job, in his words, of "providing service
to science."

46. Taylor, Principles of Scientific Management (above, n. 36), p. 126.