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OCR for page 274
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OCR for page 275
FRANCIS PEYTON ROUS
Octo her 5, ~ 879-February ~ 6, 1970
BY RENATO DULBECCO
PEYTON ROUS was awarded the Nobel Prize in 1966, when he
was eighty-six years old, for discoveries he had made fifty
years before. He was born on the 5th of October 1879 in Balti-
more, Maryland, to a family that valued humanistic education.
Thus, after the death of his father, when Peyton Rous was a
child, his mother rejected the idea of joining her family in Texas
and stayed in Baltimore, where excellent education for the
children was available. Of the two sisters of Peyton Rous, one
became a musicologist, the other a painter; and Peyton himself
had a flair for writing.
Peyton Rous enrolled in the Medical School of the recently
created Johns Hopkins University, which he attended without
special distinction. As an undergraduate he showed a naturalist's
tendency and published articles about Baltimore's flowers. After
graduating in medicine, he went to the University of Michigan,
where he began his research career in pathology, which he
perfected during a year in Dresden. In 1909 he joined the
Rockefeller Institute under Simon Flexner, to engage in cancer
research, against the opinion of influential friends who thought
it was a hopeless field. There he remained until his death. In
1921 he became co-editor (and later editor) of the Journal for
Experimental Medicine. In 1927 he was elected to the National
Academy of Sciences. He died in 1970, at the age of ninety, and
275
OCR for page 276
276
BIOGRAPHICAL MEMOIRS
is survived by his wife, Marion, and three daughters, Marion,
Ellen, and Phoebe.
In addition to the Nobel Prize, Peyton Rous received many
honors and honorary degrees, which are listed at the end of this
memoir.
The name of Peyton Rous became widely known to biolo-
gists in the fifties and sixties for his earlier discovery of a virus
causing sarcoma in chickens, which became aptly known as the
Rous Sarcoma Virus. At the time he became famous, Peyton
Rous appeared as an elderly, highly educated, gentleman with
silvery hair. But in his youth he was a very hardworking scientist
with a determined, fiery, and highly critical personality. He was
a medical man who wished to learn about cancer as a disease and
a biologist who did not want to follow the beaten track, and he
was willing to hunt for new clues in well-designed but slow
experiments.
I, like most of my contemporaries, became acquainted with
Peyton Rous's fundamental discovery in the early fifties, when
Harry Rubin came to my lab to work with the Rous Sarcoma
Virus. He started using a focus technique on the chorioallantoic
membrane of the chicken embryo, which Rous had invented
many years before. Later I had occasion to meet Peyton Rous
several times on the platform as a speaker, or across the discus-
sion table, or in his laboratory at the (then) Rockefeller Institute.
I remember the man—rather small in stature with silvery hair
and penetrating eyes. I also remember that before our first meet-
ing I was inclined to think of him as a figure of the past, but
soon changed my mind at that meeting and even more so at
subsequent ones. Clearly, he was very much alive until his very
last days, with a keen interest in new developments in virology
and cancer research. He was able to discuss his past work with
equanimity and to accept new interpretations of his data. I re-
member I suggested to him an explanation of the clonal charac-
teristic of the neoplastic transformation of papillomas in terms
OCR for page 277
FRANCIS PEYTON ROUS
277
of somatic cell genetics, a concept that was not part of cancer
research in the period of his active work. His interest was im-
mediately aroused; he asked me for a thorough clarification of
what I meant and then argued, with passion but no animosity.
... ~ ... .. ~ . . . .
- rim ~
we parted Able old friends who have found something new to
talk about. 4- -'
At the time when phage lysogeny was the domain
of a very small group of virolo~ists. I suggested to him that it
. .
might represent a good model for some features of viral cancer.
Again his interest was acute, and I had to embark on a detailed
discussion of phage integration, immunity, and lysogenic con-
version.
Peyton Rous discovered the viral etiology of a chicken sar-
coma in 1911 through his interest in tumor tr~n~nl~nt~hilirv to
1 , ~ - ~ YE
new nosts oy a nitrate. He commented: "The behaviour of the
new growth has been throughout that of a true neoplasm, for
which reason the fact of its transmission by means of a cell-free
filtrate assumes exceptional importance" (191 1~.
He fully realized from the outset that this was "a unique
and significant finding" (1911~. He also realized that the signifi-
cance of the discovery depended on the true nature of the
induced growth. As an experienced pathologist he could see
that it was a true cancer: "The (pathological) picture (of the
growth) does not in the least suggest a granuloma . . . it exhibits
to a special degree, not merely a few, but all those features by
which the malignant neoplasms are characterized" (191 1~.
For about forty years this momentous discovery had little
impact, because the minds of scientists were not prepared to
think of viruses as agents of cancer. It was expedient to say that
the chicken tumor was not a cancer, but some kind of reaction
to the virus more akin to inflammation than neoplasia, and
perhaps a peculiarity of chicken biology. Peyton Rous soon
recognized himself that the tumor would not be accepted as a
cancer because it was transmitted by a cell-free extract: "A
passing reference should perhaps be made to the ill-defined
OCR for page 278
278
BIOGRAPHICAL MEMOIRS
group of pathological products called granulomata, with which
this neoplasm of the fowl may by some be classed, owing to its
transmission by an agent separable from the tissue cells" (191 1~.
Many years later he wrote, "This disclosure (that certain chicken
tumors were proved due to viruses), which conflicted with the
negative findings in mammalian growths, was determined forth-
with as erroneous" (1952~.
One wonders how firmly in the early years Peyton Rous
himself was convinced that he had demonstrated the induction
of a cancer by viruses. The statements he made at the time are
very cautious and full of qualifications. At first he used to refer
to the "agent" that induced the sarcoma; but a year later, after
he discovered a new, different tumor transmissible by filtrate,
he proposed that the "agent is probably a living virus" (1912~.
During the years 1911-1914, Peyton Rous worked hard at
disproving the objections on the nature of the induced tumors
by isolating other viruses that induced tumors in chickens and
by carefully studying their pathology. He could show that the
tumors induced by the different viruses were capable of invad-
ing neighboring tissues and of metastasizing to distant organs;
thus they were true cancers. Moreover, each independently
isolated virus caused a tumor of a different kind. These facts
should have been convincing evidence that the growths were
specific responses of the host, yet this conclusion was not gener-
ally accepted. However, these discoveries seem to have been
convincing for Rous, who wrote, "The findings with the chicken
tumors largely demolish the theoretical basis in which objec-
tions to an extrinsic cause for cancer have been built up" (1912~.
In order to find more generally acceptable evidence, Peyton
Rous attempted to extend his observations "especially through
carefully devised experiments with the tumors of other species
of animals" (1911~. Evidently for the viral etiology to be ac-
cepted, similar findings were needed in mammals. The strategy
of Rous's future work was determined at that time. However,
OCR for page 279
FRAN CIS PEYTON ROUS
279
the extension to other species came only many years later with
Richard Shope's discovery of the rabbit papilloma virus.
In the meantime Peyton Rous studied many features of the
cell-free transmission of the tumor. Examining the effect of the
age of the host, he showed that the virus induces characteristic
foci on the chorioallantoic membrane of the chicken embryo.
This result supplied an assay for the virus that was universally
employed until the fifties, when it was superseded by the focus
formation in tissue culture.
In this extensive and careful work, Peyton Rous observed
the host resistance to the transmission of the tumor, in the form
of either absence of growth, slow growth, or normal growth
followed by regression. Other experiments showed how essen-
tial the conditions of the host are for the development of a
tumor after inoculation of the virus. From this observation
Peyton Rous began to recognize the existence of limitations to
the expression of the oncogenic potential of the virus: "How
does it happen that the sarcoma, though ultimately dependent
on an extrinsic agent, is dominated in its behaviour by the cells
composing it?" (1912~. Perhaps the agent depends "on a special
set of conditions in order that it might produce a neoplastic
change" ( 1912~. He returned later to this Point on several
occasions.
. . ,
After discovering the second chicken tumor agent, Peyton
Rous started wondering about the etiology of cancer in general:
"The demonstration that extrinsic agents are the cause of two
connective-tissue growths of the fowl which are characteristic
malignant tumors renders it necessary to suppose either that such
tumors of the fowl have an entirely different etiology from
mammalian tumors, or else that the latter are of similar origin"
(1912~. This point was also developed to a much greater extent
later on.
As further evidence for a viral nature of the chicken tumors,
the resistance of the host to the tumor cells could be separated
OCR for page 280
280
BIOGRAPHICAL MEMOIRS
from its resistance to the tumor-inducing agent. Moreover, Rous
discovered a third chicken tumor, transmissible by filtrate,
markedly different in properties from the two previously de-
scribed: "The findings with the three tumor-producing agents
have a striking similarity and it is difficult to avoid the con-
clusion that the three are of one class, whatever that class may
be.... It is perhaps not too much to say that their recognition
points to the existence of a new group of entities which cause in
chickens neoplasms of diverse characters" (1914~.
At the beginning of World War I, Peyton Rous, under the
pressure of wartime medical needs, gave up his work with
chicken tumor viruses. For the following twenty years until
1934, his interest was in the fields of blood transfusion and
attending immune reactions, liver and biliary functions, cellu-
lar functions, and vascular permeability. I will return to these
· . .
activities ater on.
A turning point in Peyton Rous's work on cancer was the
discovery of the Shope papilloma. In 1933 Richard Shope re-
ported his discovery that a mammalian tumor, the papilloma of
cottontail rabbits, was transmitted by a virus-like agent. As in
the case of the chicken tumor, Peyton Rous's first concern was
whether the papilloma was a true neoplasm. He decided that it
was, because, when the papillomas were transplanted deep in-
side the body, they developed into carcinomas that grew inva-
sively and killed the host. Furthermore, in domestic rabbits the
virus-induced papillomas often grew progressively, invading the
neighboring tissues and producing metastases, and this malig-
nant evolution could be enhanced by exposing the papillomas
to various substances, such as Scarlet Red.
These findings seem to have been for Rous the decisive
argument for the validity of his conclusions concerning the
chicken tumors, since in a mammal cancer could also be trans-
mitted by a virus. He, therefore, returned to the study of car-
cinogenesis using the papilloma virus as a new tool. He focused
OCR for page 281
FRANCIS PEYTON ROUS
281
at first on the malignant evolution of the papillomas. By careful
observations, following small hints, such as the shape of their
growths, color, or the degree of pigmentation, he showed that a
few cells in a papilloma became cancerous and generated clones,
each with different characteristics.
In trying to understand how such evolution to cancer occurs,
Peyton Rous studied the effects of tar, as both a carcinogen and
tumor promoter. He found that tar not only strongly enhanced
the induction of papillomas or carcinomas by the Shope virus
in domestic rabbits but by itself elicited similar papillomas.
Could tar papillomas also be virus-induced?
This new phase of Peyton Rous's work, although a natural
development of his earlier work, had more ambitious goals, for
it aimed at testing the hypothesis that "this disease (cancer) is
an infection.... A main attraction of this hypothesis is its
accessibility to test." However, he clearly saw that this hypothe-
sis could only be true under certain conditions, one of which is
that "a living entity responsible for such growths must require
for effectiveness a very special basis of predisposition" (1932~.
He sought to possibly disprove the infectious nature of cancer
by comparing the frequency of cancer induction by tar in the
skin of two groups of mice with different exposure to- the envi-
ronment: "The animals of one group have been placed under
conditions which would facilitate the entrance into the body of
extraneous living agents, whereas those of the others have been
sedulously protected" (1932~. The results proved "that the mouse
cancer cannot be caused by living entities reaching the body
from the surrounding world during adult life" but "fail to
exclude the possible activity of entities residing habitually in
or upon the body" (1932~. This experiment showed another re-
quirement of the hypothesis on the infectious nature of cancer:
"The supposition (that tumors in general are due to viruses or
other extraneous entities) is tenable only if such entities are
widely distributed throughout the animal population, being
OCR for page 282
282
BIOGRAPHICAL MEMOIRS
constantly present in or upon the body, like the colon bacillus
or the staphylococcus; and if their opportunity to cause tumors
is restricted by the need for very special conditions.... The
more considerable an agent is conditioned in its activity, the
more often must it be present if it is to cause disease at all"
(1934~. These words were prophetic, as shown by the recent
developments in the field; yet they were simply the result of cool,
logical assessment of the facts then in hand. However, for Peyton
Rous this hypothesis was only a guide for the experiment: "The
demonstration of the cause for the generality of tumors, what-
ever this is, waits upon the provision by the investigator of the
conditions necessary to its effectiveness" (1934~.
He tried several new approaches. One of the major tools was
still the technique of inducing skin tumors by application of
tar. He used it to create favorable cellular conditions for reveal-
ing the neoplastic potential of viral agents. Another tool was
the immunity of the infected rabbits against the Shope virus.
Peyton Rous found no demonstrable antibodies in rabbits with-
out papillomas or in those with tar papillomas or Brown-Pierce
tumors: these findings "speak decisively against the possibility
that these growths are caused by viruses antigenically related to
the one causing papillomas. Yet this does not exclude a virus
causation for them, since the sera of fowls with Chicken Tumor
I and Fujinami Sarcoma respectively, though possessed of neu-
tralizing power for the virus causing the growth carried by the
host, have no cross-neutralizing effect whatsoever" (1936~.
Shortly afterwards, in taking a bird's eye view of his past
work and of the cancer problem, he concluded: "How far should
one be led by the assumption that certain tumors may be due to
viruses? Only so far as to make tests with these growths. The
tumor problem has withstood the most corrosive reasoning. Yet
since what one thinks determines what one does in cancer
research, as in all else, it is as well to think something. And it
may prove worthwhile to think that one or more tumors of
OCR for page 283
FRAN CIS PEYTON ROUS
283
unknown causes are due to viruses" (1936~. He thus recognized
that the problem that he so clearly formulated and actively
pursued eluded experimental attack and remained unsolved. In
fact he later restated the basic question: "What is the papilloma
doing in the cancer, if anything?" (1940~.
In a renewed effort to answer this question, Peyton Rous
used as a new tool the famous line of transplantable rabbit
cancers, derived from a viral papilloma called at first "carcin-
oma V2" (1940), and then, after World War II, V X 2 because
during the war V2 "came to have another significance" (1952~.
This line did not contain infectious papilloma virus, but for
many serial transfers in rabbit it continued to elicit the produc-
tion of virus-specific antibody.
The result suggested that the virus may play a determining
role although in "masked or altered form" (1940~. This was a
new idea in virology, which had enormous developments many
years later. For the next three years, during serial transplanta-
tion from one rabbit to another, the V X 2 carcinoma continued
to elicit this immune response. However, when it was retested
after an interval of one and a half years, four and a half years
after its origin, the tumor was found unable to immunize
against the papilloma virus; the loss of this property "was not
attended by any perceptible change in the V X 2 carcinoma"
(1952~. This "wholly unexpected" result must have been quite
shattering; and Peyton Rous was led to rethink the role of the
virus in the production of the cancer. In this agonizing re-
appraisal he proposed that the virus might have undergone
"wider variation" (1952~; but he recognized that "at this un-
certain point the problem of the cause for the V X 2 carcinoma
must perforce be left" (1952~. In this way the work of Peyton
Rous went full circle: from complete ignorance on the role
of viruses in cancer to definitely establishing such a role through
brilliant discoveries, to postulating a wider and possibly general
role of viruses in spontaneous cancers, and ending up again in
OCR for page 284
284
BIOGRAPHICAL MEMOIRS
a condition of uncertainty. I should not say full circle, but
rather one turn of the helix, because the uncertainty was now
of a different kind.
The emphasis of Peyton Rous's work in the forties and fifties
shifted from the viruses to chemical carcinogens. Many articles
were dedicated to the potentiating effect of tar and other car-
cinogens on virus-induced papillomas. During this work it also
became clear that tar alone induces papillomas very similar to
those induced by the virus on normal skin or on skin pretreated
by tar. In all cases the growth showed progression, i.e., remained
benign for some time and then developed into carcinomas,
which arose in a few isolated cells. However, many observations
also showed that the role of the virus and of the chemicals was
different: "The generality of the carcinogens bring about tissue
conditions out of which tumors may or may not arise for reasons
still undetermined. They may' tee fitly called provocative car-
cinogens. The viruses, on the other hand, both initiate tumors
and determine their character and behaviour. They are actuat-
ing carcinogens" (1943~.
In a new series of experiments, Peyton Rous convincingly
demonstrated that the viral and the chemical agents have a
cooperative action, producing in combination cancers at much
higher frequency and after shorter time than either agent alone.
On the basis of this cooperation, Peyton Rous made three
important suggestions. One bears on the mechanism of carcino-
genesis. He proposed that in utero or at a young age the human
or animal body becomes invaded by viruses that "would give
no sign of their presence in most instances.... But if a provoca-
tive carcinogen happened to work on the cells with which such a
virus was associated . . . it might undergo variation and . . .
give rise to a tumor. The new pathogenic variant would not be
transmitted to other animals . . . but would be a dead-end virus,
though the harmless source virus liable to the same or other
variation would be passed on" (1943~. This hypothesis is very
OCR for page 297
FRAN CIS PEYTON ROUS
297
The effects of operation, exercise, hot weather, relief of obstruc-
tion, intercurrent disease, and other normal pathological influ-
ences. J. Exp. Med., 37: 395-420.
With G. O. Broun and P. D. McMaster. Studies on the total bile. II.
The relation of carbohydrates to the output of bile pigment. l.
Exp. Med., 37:421-29.
With P. D. McMaster and G. O. Broun. Studies on the total bile. III.
On the bile changes caused by a pressure obstacle to secretion;
and on hydrohepatosis. i. Exp. Med., 37:685-98.
With G. O. Broun and P. D. McMaster. Studies on the total bile. IV.
The enterohepatic circulation of bile pigment. I. Exp. Med., 37:
699-710.
With P. D. McMaster and D. R. Drury. The genesis of gall stones in
the dog. Proc. Soc. Exp. Biol. Med., 20:315-18.
With G. O. Broun and P. D. McMaster. Studies on the total bile. V.
The relation between blood destruction and output of bile pig-
ment. l. Exp. Med., 37:733-57.
1924
With P. D. McMaster and D. R. Drury. Observations on some causes
of gall stone formation. I. Experimental cholelithiasis in the
absence of stasis, infection, and gall bladder influences. l. Exp.
Med., 39:77-96.
With I). R. Drury and P. D. McMaster. Observations on some causes
of gall stone formation. II. On certain special nuclei of deposi-
tion in experimental cholelithiasis. l. Exp. Med., 39:97-116.
With D. R. Drury and P. D. McMaster. Observations on some causes
of gall stone formation. III. The relation of the reaction of the
bile to experimental cholelithiasis. l. Exp. Med., 39:403~5.
With P. D. McMaster. The liver requirement of the fasting or-
ganism. J. Exp. Med., 39:425-45.
The relative reaction of living mammalian tissues. Science, 60:363.
1925
The relative reaction within living mammalian tissues. I. General
features of vital staining with litmus. l. Exp. Med., 41:379-97.
The relative reaction within living mammalian tissues. II. On the
mobilization of acid material within cells, and the reaction as
influenced by the cell state. l. Exp. Med., 41 :399-411.
OCR for page 298
298
BIOGRAPHICAL MEMOIRS
The relative reaction within living mammalian tissues. IlI. Indi-
cated differences in the reaction of the blood and tissues on vital
staining with phthaleins. T. Exp. Med., 41 :451-70.
With D. R. Drury. jaundice as art expression of the physiological
wastage of corpuscles. l. Exp. Med., 4 1: 60 1-9.
With D. R. Drury. Suppression of bile as a result of impairment of
liver function. J. Exp. Med., 41:611-22.
The relative reaction within living mammalian tissues. IV. Indi-
cated differences in the reaction of the organs on vital staining
with phthaleins. l. Exp. Med., 41:739-59.
With D. R. Drury. Outlying acidosis. i. Am. Med. Assoc., 85:33-35.
The biliary aspects of liver disease. Am. l. Med. Sci., 170:625.
1926
With D. R. Drury. The relative reaction within living mammalian
tissues. V. (a) Influence of lymph-soluble tissue materials on the
significance of the coloration with some phthalein indicators. V.
(b) Influence of lymph-insoluble tissue materials on the signifi-
cance of the coloration with some phthalein indicators. J. Exp.
Med., 43:669-86, 687-701.
The relative reaction within living mammalian tissues. VI. Factors
determining the reaction of skin grafts; a study of the indicator
method of conditions within an ischemic tissue. l. Exp. Med.,
44:815-34.
With W. W. Beattie. The relative reaction within living mammalian
tissues. VII. The influence of changes in the reaction of the
blood upon the reaction of the tissues. l. Exp. Med., 44:835-54.
1927
With D. R. Drury and W. W. Beattie. The relative reaction within
living mammalian tissues. VIII. On the course of the tissue aci-
dosis secondary to blood acidosis induced with hydrochloric
acid. l. Exp. Med., 45:23-39.
With D. R. Drury and W. W. Beattie. The relative reaction within
living mammalian tissues. IX. On the tissue reaction as influ-
enced by inhalations of CO2 and by overbreathing. J. Exp. Med.,
45:41-58.
Pathology and the glare of the future. Reprinted from Contributions
to Medical Science (Dedicated to Aldred Scott Warthin), ed. by
Willard J. Stone, pp. 19-22. Ann Arbor, Mich.: George Wahr.
OCR for page 299
FRANCIS PEYTON ROUS
1929
299
With D. R. Drury. Outlying acidosis due to functional ischemia. l.
Exp. Med., 49:435-60.
The Modern Dance of Death. (The Linacre Lecture) London:
Cambridge Univ. Press. 51 pp.
With H. P. Gilding. The meaning of Bier's spots. Proc. Soc. Exp.
Biol. Med., 26:497-98.
With H. P. Gilding. Studies of tissue maintenance. I. The changes
with diminished blood bulk. J. Exp. Med., 50:189-211.
With H. P. Gilding. Studies of tissue maintenance. III. Persisting
bloodlessness after functional ischemia. l. Exp. Med., 50:471-87.
With H. P. Gilding. The final response of the small cutaneous ves-
sels. l. Exp. Med., 50:489-512.
1930
With H. P. Gilding. Is the local vasodilatation after different tissue
injuries referable to a single cause? J. Exp. Med., 51:27-39~.
With H P. Gilding and F. Smith. The gradient of vascular perme-
ability. J. Exp. Med., 51: 807-30.
1931
With F. Smith. The gradient of vascular permeability. II. The con-
ditions in frog and chicken muscle, and in the mammalian dia-
phragm. J. Exp. Med., 53:195-217.
With F. Smith. The gradient of vascular permeability. III. The
gradient along the capillaries and venules of frog skin. l. Exp.
Med., 53:219-42.
With F. Smith. The gradient of vascular permeability. IV. The per-
meability of the cutaneous venules and its functional significance.
J. Exp. Med., 54:499 514.
1932
With P. D. McMaster and S. S. Hudack. The relation of hydrostatic
pressure to the gradient of capillary permeability. l. Exp. Med.,
55:203-21.
With E. Botsford. The incidence of cancer in tarred and sheltered
mice. J. Exp. Med., 55:247-66.
OCR for page 300
300
BIOGRAPHICAL MEMOIRS
1933
With P. D. McMaster and S. S. Hudack. The fixation of certain
viruses on the cells of susceptible animals and the protection
afforded by such cells. Proc. Soc. Exp. Biol. Med., 31:90-91.
1934
Withy. W. Beard. The neoplastic traits of a mammalian growth due
to a filterable virus the Shope rabbit papilloma. Science, 79:
437-38.
With i. W. Beard. Selection with the magnet and cultivation of
reticuloendothelial cells (Kupffer cells). J. Exp. Med., 59:577-91.
With i. W. Beard. The characters of Kupffer cells living in vitro.
J. Exp. Med., 59~:593-607.
With l. W. Beard. A virus-induced mammalian growth with the
characters of a tumor (the Shope rabbit papilloma). I. The
growth on implantation within favorable hosts. l. Exp. Med.,
60:701-22.
With I. W. Beard. A virus-induced mammalian growth with the
characters of a tumor (the Shope rabbit papilloma). II. Experi-
mental alterations of the growth on the skin: morphological
considerations: the phenomena of retrogression. J. Exp. Med.,
60:723-37.
With i. W. Beard. A virus-induced mammalian growth with the
characters of a tumor (the Shope rabbit papilloma). III. Further
characters of the growth: general discussion. l. Exp. Med., 60:
741-66.
1935
With l. W. Beard. Carcinomatous changes in virus-induced papillo-
mas of the skin of the rabbit. Proc. Soc. Exp. Biol. Med., 32:
578-80.
With P. D. McMaster and S. S. Hudack. The fixation and protection
of viruses by the cells of susceptible animals. i. Exp. Med., 61:
657-88.
With i. W. Beard. The progression to carcinoma of virus-induced
rabbit papillomas (Shope). J. Exp. Med., 62:523~8.
With l. W. Beard. Effectiveness of the Shope papilloma virus in vari-
ous American rabbits. Proc. Soc. Exp. Biol. Med., 33:191-93.
-
OCR for page 301
FRANCIS PEYTON ROUS
301
With John G. Kidd and l. W. Beard. Certain factors determining the
course of virus-induced tumors. Proc. Soc. Exp. Biol. Med., 33:
193-95.
With J. W. Beard. A comparison of the tar tumors of rabbits and the
virus-induced tumors. Proc. Soc. Exp. Biol. Med., 33:358-60.
1936
With l. G. Kidd. The carcinogenic effect of a virus upon tarred skin.
Science, 83:468-69.
With l. G. Kidd and l. W. Beard. Serological reactions with a virus
causing rabbit papillomas which become cancerous. I. Tests of
the blood of animals carrying the papilloma. l. Exp. Med., 64:
63-77.
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With l. G. Kidd and i. W. Beard. Serological reactions with a virus
causing rabbit papillomas which become cancerous. II. Tests of
the blood of animals carrying various epithelial tumors. J. Exp.
Med., 64:79-96.
With J. G. Kidd and l. W. Beard. Observations on the relation of
the virus causing rabbit papillomas to the cancers deriving
therefrom. I. The influence of the host species and of the
pathogenic activity and concentration of the virus. J. Exp. Med.,
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With l. W. Beard and I. G. Kidd. Observations on the relation of
the virus causing rabbit papillomas to the cancers deriving
therefrom. II. The evidence provided by the tumors; general
considerations. J. Exp. Med., 64:401-24.
The virus tumors and the tumor problem. (Harvey Lecture) Ameri-
can Journal of Cancer, 28:233-71.
1937
With J. G. Kidd. Effect of the papilloma virus (Shope) upon the tar
warts of rabbits. Proc. Soc. Exp. Biol. Med., 37: ~ 18-20.
1938
With l. G. Kidd. The carcinogenic effect of a papilloma virus on
the tarred skin of rabbits. I. Description of the phenomenon. l.
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With l. W. Beard. The fate of vaccinia virus on cultivation in vitro
with Kupffer cells (reticulo-endothelial cells). J. Exp. Med., 67:
883-910.
With l. G. Kidd. The carcinogenic effect of a papilloma virus on
the tarred skin of rabbits. II. Major factors determining the
phenomenon; the manifold effects of tarring. l. Exp. Med., 68:
529-61.
1939
With l. G. Kidd. A comparison of virus-induced rabbit tumors with
the tumors of unknown cause elicited by tarring. i. Exp. Med.,
69: 399-424.
1940
With J. G. Kidd. Cancers deriving from the virus papillomas of wild
rabbits under natural conditions. l. Exp. Med., 71:469-93.
With i. G. Kidd. The activating, transforming, and carcinogenic
effects of the rabbit papilloma virus (Shope) upon implanted
tar tumors. l. Exp. Med., 7 1: 787-8 1 1 .
With J. G. Kidd. A transplantable rabbit carcinoma originating in
a virus-induced papilloma and containing the virus in masked
or altered form. l. Exp. Med., 71 :813-37.
1941
With J. G. Kidd. Conditional neoplasms and subthreshold neo-
plastic states. A study of the tar tumors of rabbits. J. Exp. Med.,
73:365-89.
With Ian MacKenzie. The experimental disclosure of latent neo-
plastic changes in tarred skin. J. Exp. Med., 73:391~15.
The conditions determining cancer. (The William Henry Welch
Lecture, I) J. Mt. Sinai Hosp., 8:184 - 85.
The known causes of cancer. (The William Henry Welch Lecture,
II) J. Mt. Sinai Hosp., 8: 186.
With W. F. Friedewald. The carginogenic effect of methylcholan
threne and of tar on rabbit papillomas due to a virus. Science
94:495-96.
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1943
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Viruses and tumors. In: Virus Diseases, p. 147. Ithaca, N.Y.: Cornell
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The nearer causes of cancer. i. Am. Med. Assoc., 122:573-84.
1944
With W. F. Friedewald. The effect of chemical carcinogens on virus-
inducedrabbit papillomas. l. Exp. Med., 79:511-37.
With W. F. Friedewald. The initiating and promoting elements in
tumor production. An analysis of the effects of tar, benzpyrene,
and methylcholanthrene on rabbit skin. J. Exp. Med., 80: 101-25.
With W. F. Friedewald. The determining influence of tar, benzpy-
rene, and methylcholanthrene on the character of the benign
tumors induced therewith in rabbit skin. l. Exp. Med., 80:
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lg45
With W. E. Smith. The neoplastic potentialities of mouse embryo
tissues. I. The findings with skin of C strain embryos transplanted
to adult animals. l. Exp. Med., 81:597-619.
The neoplastic potentialities of mouse embryo tissues. II. Contribu-
tory experiments; results with skin of C3H and Webster-Swiss
embryos; general considerations. J. Exp. Med., 81:621~5.
1946
The activation of skin grafts. l. Exp. Med., 83:383-99.
Concerning the cancer problem. American Scientist, 34 (July>:329.
Simon Flexner and the Journal of Experimental Medicine. J. Exp.
Med., 84(1):i.
1947
Recent advances in cancer research. Bulletin of the New York
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The lamentable decline in self-satisfaction. Proceedings of the Cha-
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Karl Landsteiner, 1868-1943. Obit. Not. Fell. R. Soc. Lond., 5:295-
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1948
Simon Flexner and medical discovery. Science, 107:611-13.
With W. E. Smith. The neoplastic potentialities of mouse embryo
tissues. IV. Lung adenomas in baby mice as result of prenatal
exposure to urethane. i. Exp. Med., 88:529-54.
1949
Robert Gladding Green~41895-1947~. Science, 109:93.
Simon Flexner, 1863-1946. Obit. Not. Fell. R. Soc. Lond., 6:409-30.
1950
With W. F. Friedewald. The pathogenesis of deferred cancer. A
study of the after-effects of methylcholanthrene upon rabbit
skin. J. Exp. Med., 91:459 83.
1951
With S. Rogers. Joint action of a chemical carcinogen and a neoplas-
tic virus to induce cancer in rabbits. Results of exposing epi-
dermal cells to a carcinogenic hydrocarbon at time of infection
with the Shope papilloma virus. i. Exp. Med., 93:459-88.
1952
With S. Rogers. The occurrence in tarred rabbit skin of minor,
almost imperceptible, neoplastic changes. Cancer Res., 12:292.
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With W. E. Smith and J. G. Kidd. Experiments on the cause of the
rabbit carcinomas derived from virus-induced papillomas. I.
Propagation of several of the cancers in sucklings, with etiologi-
cal tests. J. Exp. Med., 9~5:299-317.
What cancer research has done. The Listener, 48: 138-42 (issue
dated 24 July).
With J. G. Kidd and W. E. Smith. Experiments on the cause of the
rabbit carcinomas derived from virus-induced papillomas. II.
Loss by the V X 2 carcinoma of the power to immunize hosts
against the papilloma virus. J. Exp. Med., 96:159-74.
Cancer research as viewed along the years. Acta Physiologica Latino-
americana, 3: 18~87.
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With K. Dumbell. Are carcinogens responsible for the superimposed
neoplastic changes occurring in mouse tumor cells? The effect
of methylcholanthrene and urethane on pulmonary adenomas
and of methylcholanthrene on mammary carcinomas. l. Exp.
Med., 102:517-43.
1958
With R. A. Allen. Fatal keratomas due to deep homografts of the
benign papillomas of tarred mouse skin. Normal proclivities and
neoplastic disabilities as determinants of tumor course. l. Exp.
Med., 107:63-85.
1959
Surmise and fact on the nature of cancer. Nature, Land., 183:1357-
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1960
Leo Loeb, 1869-1959. Cancer, 13: 3-4.
The possible role of viruses in cancer. Opening remarks and sum-
mary of informal discussions (first session). Cancer Res., 20:672-
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Charles Oberling, research worker on the nature of cancer. Science,
132: 1534-35.
1961
The scope of carcinogenesis. Extrait de Acta Union Internationale
Contre le Cancer, 17: 262-65.
1962
With l. S. Henderson. The plating of tumor components on the
subcutaneous expanses of young mice: findings with benign and
malignant epidermal growths and with mammary carcinomas.
J. Exp. Med., 115: 1221-29.
The disagreement amongst doctors. In: On Cancer and Hormones,
p. 49. Chicago: Univ. of Chicago Press. Reprinted in Midway,
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1964
Henry James and the mouse. Perspect. Biol. Med., 7:433-34.
With l. S. Henderson. Further experiments on the cause of sequen-
tial neoplastic changes. The effects of 20-methylcholanthrene on
transplanted epidermal mouse papillomas and the derivative
carcinomas. J. Exp. Med., 120: 197-221.
1965
Viruses and tumour causation: an appraisal of
Nature, Land., 207:457-63.
present knowledge.
The viruses and us. In: Perspectives in Virology, ed. by Morris Pol-
lard, vol. 4, pp. 305-8. New York: Hoeber Medical Division,
Harper & Row Pubs., Inc.
A great friend: George de Hevesy. International Journal of Applied
Radiation and Isotopes, 16:516-18.
1966
The lamentable decline in self-satisfaction. Perspect. Biol. Med., 9:
439-49.
Biography and speeches at the Nobel Banquet. In: Les Prix Nobel
en 1966. Stockholm: Kungl. Boktryckeriet P. A. Norstedt 8c Soner.
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1967
The fly in the social ointment. Perspect. Biol. Med., 11: 1-8.
The challenge to man of the neoplastic cell. Cancer Res., 27:1919,
1960; also in Science, 157: 24-28.
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Representative terms from entire chapter:
biographical memoirs
