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CLARENCE COOK LITTLE October 6, 1888-December 22, 1971 BY GEORGE D. SNELL DR. CLARENCE COOK LI~LE died December 22, 1971, in Ells- worth, Maine, at the age of eighty-three. A leader in edu- cation, in the national effort to understand and control cancer, and in the development of mammalian genetics, Dr. Little inspired in the many people who knew him not only admira- tion but warm personal friendship. He is survived by his wife, Beatrice, two sons, two daughters, and nine grandchildren. Dr. Little was born in Brookline, Massachusetts, October 6, 1888. He was a member of an old Boston family and a de- scendent of Paul Revere. His boyhood was spent on the family estate in Brookline, where a variety of animals and pets, includ- ing his own mice and prize pigeons, provided an early exposure to biology. He was educated at Noble and Greenough School and Harvard College and continued at Harvard as a graduate student in mammalian genetics under Dr. William E. Castle, who pioneered in the application of Mendelian principles to mice and rabbits. During his senior year at Harvard, Pete, as he was known by his college friends, was captain of the track team. Dr. Castle related later how this handsome team captain signed up for his genetics course and soon had persuaded most of the team to sign up with him. While still a graduate student at Harvard, Dr. Little became interested in studies being carried out by Professor Tyzzer at 241

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242 BIOGRAPHICAL MEMOIRS Harvard Medical School on the inheritance of susceptibility and resistance to tumor transplants in mice. This work led him to prepare a paper, published in Science, describing a type of multifactor inheritance that anticipated present concepts of histocompatibility genetics. Little's major research interests transplantation, the cancer problem, and mammalian and es- pecially murine geneticswere established during this period. Following the award of his D. Sc. in 1914, Dr. Little held various positions at Harvard: secretary to President Lowell, assistant dean of the college, and acting marshal!. With the en- trance of the United States into the First World War, he en- listed in the army and trained at Plattsburgh, New York. Subsequently he was assigned to administrative duty in Wash- ington with the Signal Corps, later to become the U.S. Air Force. He was discharged in 1918 with the rank of Major. After his war service, Dr. Little spent three years at the Station for Experimental Evolution in Cold Spring Harbor, New York, serving during the last year as assistant director. Throughout this period Dr. Little maintained his interest in mammalian genetics and cancer. He published numerous papers and even during the war saw to it that his animal colony was maintained. Perhaps his most lasting contribution was the establishment of the first inbred strains of mice. Inbreeding had been extensively studied in corn, and Jennings had ex- aminecl mathematically the expected increase in homozygosis. The mouse was a logical choice for inbreeding experiments with a mammal, perhaps, in fact, an especially fortunate choice, since wild populations of mice form small colonies with con- siderable inbreeding so that the accumulation of deleterious recessive genes is restricted. But successful establishment of a homozygous strain required careful selection from a colony of adequate size. Dr. Little's pioneer inbreeding efforts resulted in two highly successful inbred strains, the dilute brown (DBA) strain, begun when he was still at Harvard, and the black

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CLAREN CE COOK LITTLE 243 (CS7BL) strain, started at Cold Spring Harbor. The genetic uniformity of these and the dozens of other lines subsequently produced in many laboratories makes them a research tool of major importance. The C57BL strain heads the list in popu- larityworldwide annual use certainly exceeds one million mice. The DBA strain is not far behind. The time was less propitious for another project that Dr. Little undertook at Cold Spring Harbor. In collaboration with Halsey Bagg he attempted to induce mutations in mice with X rays. Hermann Muller was to win the Nobel Prize in 1946 for a similar experiment with Drosophila, but with mice the number of gametes that it was feasible to test was too small; also the X-ray dose used was probably too low. Two variants appeared, but at least one of these also turned up in the con- trols. In 1922, at the age of thirty-three, Dr. Little became presi- dent of the University of Maine. He was at this time the youngest college president in the country. Perhaps his most successful innovation during the three years that he held this office was the establishment of Freshman Week. This was held prior to the opening of college and was "designed to instruct all freshmen in methods of study, in choice of courses, and in the aims and value of college work as well as to give an oppor- tunity for the study of the individual freshman in order to recognize, measure, and in so far as possible begin to utilize his particular abilities, and to avoid or to bolster up his weak- nesses." The success of this institution is attested to by its permanence and its imitation by other universities. Although there was some growth in the university plant during Dr. Little's term of office, he was not as successful in obtaining money from the legislature as he had hoped to be. One of Dr. Little's stipulations in accepting the University of Maine presidency was that he have funds and facilities to continue his biological research. Several young men whom he

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244 BIOGRAPHICAL MEMOIRS interested in biology during this period remained associated with him for years. He also succeeded in establishing at Bar Harbor, Maine, a summer laboratory on the site where The Jackson Laboratory was later to be built. After three years at the University of Maine, Dr. Little was offered and accepted the presidency of the University of Mich- igan. His appointment provided "an unprecedented $5000 for research assistance," testimony to his determination to continue his research. He was later able to add substantial support from outside sources. Again his tenure of office was marked by inno- vation and attempted innovation. A Freshman Week was in- troduced; a School of Forestry and a Department of Post- graduate Medicine were established; the first faculty research fund was created, and research expanded substantially. A plan to enroll all freshmen and sophomores in a separate University College under its own dean encountered a barrage of faculty criticism and was dropped. Lack of funds rather than active opposition was principally responsible for the demise of a plan for the erection of dormitories housing a few instructors or professors as well as students and designed to serve as small residential colleges. The latter plan was typical of Dr. Little's interest in the welfare of the undergraduate. A representative group of stu- dents met regularly in his home. He worked successfully for better intramural athletic facilities that could serve the student body as a whole. Less popular in some quarters was a ban on liquor in fraternity houses and, with some exceptions, on the use of autos by students. But probably nothing stirred up more controversy than Little's views on birth control. He spoke out for this boldly and repeatedly. Many people were not ready for such frank talk, and some bitter criticism resulted. The official history of the university refers to his presidency as a "stormy term" and

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CLARENCE COOK LITTLE 245 "brilliant but tactless," but in retrospect it appears that his successes were substantial and his failures prophetic. The year 1929 was a turning point in Dr. Little's life. In January of that year he submitted his resignation to the Regents of the University of Michigan. He also was divorced from his first wife after eighteen years of marriage and three children. Doubtless his divorce had something to do with his break with the university, as did the antagonism he had aroused in some quarters among the faculty. Perhaps he had decided also that ins talent lay In pioneering and not in routine administration. '_ . 1 _ . ~ ~ . With financial help from the Jackson and Ford families of Detroit and Mount Desert Island, he turned to his first love, research, and set out to create in Bar Harbor a laboratory for the study of mammalian genetics and cancer. When Roscoe B. Jackson, one of the major donors, died, the laboratory was named in his honor. The laboratory was staffed by a group of six young men and one woman who had worked with "Prexy," as he was still called, during his years as college president. The first major project undertaken by the staff was a study of the genetics of tissue transplantation. Crosses were made between the now highly inbred strains of mice, and data gathered on the growth of transplantable tumors in the parental and various hybrid gener- ations. The existence of multiple genes for susceptibility and resistance, subsequently called histocompatibility penes, was thereby established. Another project took advantage of the great difference in mammary tumor incidence between some of the inbred strains. In a cross between high and low strains, it was found that tumor incidence of the first hybrid generation was determined by the maternal parent. Subsequent foster nursing experiments implicated some agent transmitted through the mother's milk. Dr. Little at the time was under the in- fluence of the antivirus school of thoughtthe word virus was

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246 BIOGRAPHICAL MEMOIRS taboo, as at least one young staff member discoveredbut other laboratories picked up the work and proved the existence of a mammary tumor virus. In these early days, the research at the laboratory, despite its substantial success, was not carried on in easy circumstances. Nineteen twenty-nine was the year when the stock market broke. After a brief honeymoon, the deepening depression cut off sources of support. The research continued, but on a curtailed basis while the staff turned to fishing, gardening, and canning to provide food. It was at this time that the laboratory initiated the sale of its inbred strains to other investigators, an activity that ultimately became both a major service to re- searchers all over the world and a much needed source of un- committed income. The depression finally passed. Dr. Little initiated a program of modest expansion that ultimately was to change the char- acter of the laboratory considerably, but for the first two decades of its existence its small size and location in "down-east" Maine permitted a mode of life that he and his associates found much to their liking. Dr. Little was an enthusiastic outdoors- man, a knowledgeable ornithologist, and an accomplished fisher- man. The Maine countryside provided an ideal setting for these interests. He raised a strain of dachshunds that his father had first brought to this country and was in demand as a judge at dog shows. The life at the laboratory was kept informal. During the winter there were monthly parties, with games and refreshments, in which all employee families participated. If the games lagged, which they seldom did, Dr. Little could always liven the occasion with some good stories. In the warmer seasons there might be a laboratory picnic at which he could still display his prowess in a footrace. World War II took a number of workers away from the laboratory and led to a greatly increased production of mice suitable for the study of

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CLARENCE COOK LITTLE 247 tropical diseases, but the research went on, even though cur- tailed. It was during this same early period that Dr. Little started a program of summer training in research for precollege and college students. This program was ultimately to expand con- siderably. Its numerous alumni, many of them now physicians or engaged in biological research, still refer fondly to Dr. Little as "Prexy." With the end of the war the laboratory seemed headed for a period of substantial expansion when disaster struck a second time. The main laboratory building was largely destroyed in the forest fire of 1947 that burnt part of the town of Bar Harbor and many summer estates and hotels. The mice were wiped out excepting a few in a fireproof section of the building. Resisting pressure from friends to relocate at some major research center, Dr. Little, with the enthusiastic agreement of the staff, deter- mined to rebuild in Bar Harbor. Part of the staff moved to temporary quarters in other laboratories, part to a remodeled barn on a summer estate that had been donated earlier. The inbred strains of mice flooded back from laboratories around the world, and potential grantors heard, as they never would have otherwise, of their essential value to hundreds of re- searchers. Within two and one half years the laboratory was housed in far better quarters than it had enjoyed before the fire, and Dr. Little was able to see the staff expand and the research grow and diversify. One project in which Dr. Little took particular pleasure was the Behavior Study, centered in the barns of the estate already mentioned. Because of the favorable location and Dr. Little's knowledge of genetics and of dogs, Alan Gregg of the Rockefeller Foundation planned with him the creation of a center for the study of behavioral genetics. The project was started with colonies of several breeds of dogs, but inbred mice

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248 BIOGRAPHICAL MEMOIRS were later included with considerable profit. Dr. Little followed the project with interest and found time to study the segrega- tion of canine coat color genes in the second and third genera- tion hybrids of the various breeds. The founding and direction of a laboratory would have been enough of a career for most men, but Dr. Little found the rime and energy for additional major undertakings. In 1929 he became managing director of the American Cancer Society and retained this position till 1945. In the fall of 1930 he traveled extensively throughout western Europe, studying methods of cancer research and care. He was impressed by the long-term view of European cancer workers and urged the de- sirability of a cancer research program in the United States with similar orientation. He also stressed the need for better facilities for cancer patients and for doctor education in cancer detection and care. In 1935, with these goals substantially at- tained, he led in the organization of the Women's Field Army, dedicated to lay education concerning cancer. This had a tremendous influence in changing the public attitude toward cancer and in encouraging early diagnoses. Dr. Little's recognized scientific accomplishments and ability as a leader, his impressive good looks, his warm personality, and his talents as a public speaker and raconteur naturally led him into other positions and~activities. He was twice president of the American Association of Cancer Research and was influ- ential in creating Cancer Research as its official journal. At one time or another he also served as president of the American Eugenics Society, the American Birth Control League, and the American Euthanasia Society. He was for years a warden in the Bar Harbor Episcopal Church. He was in demand as a speaker and always drew a good audience at local affairs, including the occasional church service at which he gladly filled in for the rector. In 1937 Dr. Little was appointed as one of the six original members of the National Advisory Cancer Council, a

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CLARENCE COOK LITTLE 249 body created by the act of Congress that established the National Cancer Institute. The council played an influential role in setting the policies for cancer research in this country. There were considerable differences of opinion within the council. Dr. Little appears to have been one of the active supporters of the grants-in-aid and peer-review systems that have done so much to further biomedical research in this country. In 1954, shortly before his retirement as director of The Jackson Laboratory, Dr. Little accepted a position as scientific director of the Tobacco Industrial Research Committee, a posi- tion he held until his death. Because of the link between cigarette smoking and cancer, already suspected at the time, he was widely criticized for accepting this position. Doubtless there were many reasons back of his decision. It did have at least two positive aspects. It gave him continuing opportunity, and probably considerable freedom, to influence biomedical research through the disbursement of funds; by providing an outlet for his still considerable energies, it enabled him to make a complete break with the laboratory, giving his successor a free hand. Dr. Little was a member of the American Academy of Arts and Sciences and the National Academy of Sciences, to which he was elected in 1945, as well as of various scientific societies. He was the recipient of numerous honorary degrees. The Clarence Cook Little Hall at the University of Maine, the Clarence Cook Little Science Building at the University of Michigan, and most recently the Clarence Cook Little Library and Conference Center at The Jackson Laboratory were named in his honor. In both science and education, Dr. Little was perhaps more the originator than the exploiter of new developments. He preferred the broad view to attention to detail. But despite his diversity of interests, he found the time to be a productive scientist. He was the author of 188 papers, three books on

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250 BIOGRAPHICAL MEMOIRS cancer directed primarily at the layman, and a book on coat color in dogs. Of his scientific achievements, perhaps four stand out: the development of inbred strains of mice and the demonstration of their value in medical and biological research; the formulation of the genetic theory of susceptibility and resistance to tissue transplants; the discovery of the milk-trans- mitted murine mammary tumor incisor; and the establishment, with Rockefeller Foundation initiative and support, of a study of the genetics of behavior. Of necessity, Dr. Little's personal participation in these projects decreased as his executive duties increased. But if his varied administrative responsibilities nar- rowed his own opportunities for scientific exploration, he used them, with warmth and wisdom, to open the doors so that younger men could reach for new horizons. Perhaps this was his greatest contribution.

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CLARENCE COOK LITTLE 1918 253 Color inheritance in cats with special reference to the colors black, yellow, and tortoise-shell. i. Genet., 8:279-90. 1919 A note on the fate of individuals homozygous for certain color factors in mice. Am. Nat., 53:185-87. Some factors influencing the human sex ratio. Med., 16:127-30. Proc. Soc. Exp. Biol. With E. E. ~ones. The inheritance of coat color in Great Danes. i. Hered., 10: 309-20. 1920 Alternative explanations for exceptional color classes in doves and canaries. Am. Nat., 54:162-75. Is there linkage between the genes for yellow and for black in mice? Am. Nat., 54:267-70. Note on the occurrence of a probable sex-linked lethal factor in mammals. Am. Nat., 54:457-60. With L. C. Strong. Tests for physiological differences in trans- plantable tumors. Proc. Soc. Exp. Biol. Med., 18:45~8. A note on the human sex ratio. Proc. Natl. Acad. Sci., 6:250-53. Factors influencing the growth of a transplantable tumor in mice. J. Exp. Zool., 31:307-26. The heredity of susceptibility to a transplantable sarcoma (~.W.B.) of the Japanese waltzing mouse. Science, 51:467-68. 1921 Keport of the committee on genetic form and nomenclature. Am. Nat., 55:175-78. Evidence for sex-linked lethal factors in man. Med., 18:111-15. Proc. Soc. Exp. Biol. Non-disjunction of the fourth chromosome of Drosophila. Science, 53:167. 1922 With B. W. Johnson. The inheritance of susceptibility to implants of splenic tissue in mice. I. Japanese waltzing mice, albinos, and their F1 generation hybrids. Proc. Soc. Exp. Biol. Med., 19: 163-67.

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254 BIOGRAPHICAL MEMOIRS Relation between research in human heredity and experimental genetics. Sci. Mon., 14:401-14. 1923 Congenital and acquired predisposition and heredity. Abt's Pedi- atrics, 1: 1 7 1-256. With H. i. Bagg. The occurrence of two heritable types of ab- normality among the descendants of x-rayed mice. Am. l. Roentgen Radium Ther., 10:975-89. Inheritance of a predisposition to cancer in man. Eugenics, Ge- netics, and Family, 1:186. With E. E. Jones. The effect of selection upon a Mendelian ratio. Genetics, 8:1-26. i 1924 With H. J. Bagg. Hereditary and structural defects in the descend- ants of mice treated with Roentgen-ray irradiation. American Journal of Anatomy, 33:119-45. With L. H. Snyder and M. Schneider. ~ ~ . ~ ~ ~ ~ A report of a histological Truly OI one eyes ana gonads ot mice treated with a tight dockage of x-rays. Am. Nat., 58:383-84. The genetics of tissue transplantation in mammals. 8:75-95. be, ^ ~ ~~ ~~ = J. Cancer Res., With L. C. Strong. Genetic studies on the transplantation of two adenocarcinomata. J. Exp. Zool., 41:93-114. With H. l. Bagg. The occurrence of four inheritable morpho- logical variations in mice and their possible relation to treatment with x-rays. J. Exp. Zool., 41:45-91. With J. M. Murray and W. T. Bovie. Influence of ultra-violet light on nutrition in poultry. Maine Agricultural Experiment Sta- tion Bulletin, 320:141-64. 1925 Inaugural address of the president of the University of Michigan. School and Society, 22:1-16. 1926 Preparation and practice in medical education. 4:781-87. Ann. Clin. Med., A discussion of certain phases of sterility. Ann. Clin. Med., b:1-4.

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CLARENCE COOK LITTLE Genetic investigations and the cancer problem. Review, 8: 130-36. 1927 255 Commonwealth Preliminary report on a species cross in rodents, Mus musculus x Mus wagneri. Papers of Michigan Academic Sciences, Arts and Letters, 8: 393-99. Notes on a species cross in mice and on an hypothesis concerning the quantitative potentiality of genes. Science, 66:542-43. 1928 Report of Committee on Formal Education of the American Eugenics Society, Inc. New Haven, The Society. Agents modifying the germ plasm. Surgery, Gynecology and Ob- stetrics, 46: 155-58. Shall we live longer and should we? (president's address) Proceed- ings of 3d Race Betterment Conference January), pp. 5-14. Battle Creek, Michigan, Race Betterment Foundation. Evidence that cancer is not a simple Mendelian recessive. l. Can- cer Res., 12:30-46. Opportunities for research in mammalian genetics. Sigma Xi Q., 16: 16-35. Opportunities for research in mammalian genetics. Sci. Mon., 26: 521-34. lD31 Education in cancer. Am. l. Cancer, 15:280-83. The present status of the cancer problem. Annals of Surgery, 93: 11-16. The effects of selection on eye and foot abnormalities occurring among the descendants of x-rayed mice. Am. Nat., 65:370-75. The role of heredity in determining the incidence and growth of cancer. Am. J. Cancer, 15: 2780-89. With R. A. Hicks. The blood relationship of four strains of mice. Genetics, 16:397-421. 1932 With B. W. McPheters. The incidence of mammary cancer in a cross between two strains of mice. Am. Nat., 66:568-71. With B. W. McPheters. Further studies on the genetics of ab-

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256 BIOGRAPHICAL MEMOIRS normalities appearing in the descendants of x-rayed mice. Ge- netics, 17: 674-88. Cancer survey of St. Louis and St. Louis County, Missouri, 1931. Journal of the Missouri Medical Association, 29:249-75. 1933 Individuality and the hereditary process in mammals. Recordings of the Genetic Society of America, 2:65. With B. W. McPheters. Hound-eared mice. I- Hered., 24:157-58. Variability and individuality. Science, 77:195-97. The relation of the American Society for the Control of Cancer to radiologists. Am. i. Roentgen Radium Ther., 30:723-26. Not dead but sleeping. I. Hered., 24:149-50. The challenge of cancer. Maine Medical Journal, 24:165-68. The existence of non-chromosomal influence in the incidence of mammary tumors in mice. Science, 78 :465-66. 1934 How to educate women to recognize breast tumors. Bull. Am. Cancer Soc., August, 3 pp. Inheritance in Toy Griffons. J. Hered., 25:198-200. With P. Weir. The incidence of uterine cancer in Jews and Gentiles. I. Hered., 25 :277-80. The relation of coat color to the spontaneous incidence of mam- mary tumors in mice. I. Exp. Med., 59:229-50. The bearing of genetic work with transplanted tumors on the ge- netics of spontaneous tumors in mice. Am. I. Cancer, 22:578-85. Education and cancer control. International Journal of Medicine and Surgery, 47: 49-50. White cats and deafness. Nature, 133:215. 1935 With S. G. Warner. Failure to transmit carcinogenic agents from the pregnant mouse embryos in utero. Proc. Soc. Exp. Biol. Med., 32:866-69. With W. S. Murray. The genetics of mammary tumor incidence in mice. Genetics, 20:466-96. With W. S. Murray. Further data on the existence of extra- chromosomal influence on the incidence of mammary tumors in mice. Science, 82:228-30.

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CLARET CE COOK LITTLE 257 With A. M. Cloudman. A laboratory test of "Hoxin" as a claimed cancer "cure." J. Am. Med. Assoc., 104: 1815. Some recent advances in cancer research. Sigma Xi Q., 23:128-34. lg36 Applications of biology to human affairs. J. Hered., 27: 317-18. With A. M. Cloudman. The genetics of tumor formation in mice, in relation to the gene T for brachyury. I. Genet., 32:487-504. Charles Velmar Green. Science, 83: 543. With W. S. Murray. Extrachromosomal influence in relation to the incidence of mammary and non-mammary tumors in mice. Am. I. Cancer, 27:516-18. The present status of our knowledge of heredity and cancer. I. Am. Med. Assoc.,, 106: 2234-35. The constitutional factor in the incidence of mammary tumors. Am. J. Cancer, 27:551-55. Genetics in relation to carcinoma. Proceedings of the StaR Meet- ing of the Mayo Clinic, 11:782-83. 1937 The genetics of spontaneous mammary carcinoma in mice. Occas. Publ. Am. Assoc. Adv. Sci., 4:17-21. With A. M. Cloudman and i. l. Bittner. The relationship between the histology of spontaneous mouse tumors and the genetic constitution of the animals in which they arise. Occas. Publ. Am. Assoc. Adv. Sci., 4:37-41. The social significance of cancer. Occas. Publ. Am. Assoc. Adv. Sci., 4:242-45. Biology of cancer. Proceedings of Annual Congress on Medical Education, February 15-16, pp. 12-14. With I. J. Bittner. The transmission of breast and lung cancer in mice. I. Hered., 28: 117-21. With A. M. Cloudman. The occurrence of a dominant spotting mutation in the house mouse. Proc. Natl. Acad. Sci., 23:535-37. 1938 Influence of intrinsic factors on development of tumors in mice. University of Wisconsin, Symposium on Cancer, pp. 20-31. Madison, University of Wisconsin Press.

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258 B I O G R A P H I C A L M E M O I R S With i. H. Mowat. Effect of choline chloride on oestrus cycle of mice. Proc. Soc. Exp. Biol. Med., 39:211-12. Recent advances in research on biology of cancer. Journal of Medicine, 18:567-72. With S. P. Reimann. Dialogue on the relations of genetics and experimental embryology to neoplasia. American Journal of Clinical Pathology, 8: 109-19. Fundamental cancer research. Report of a committee appointed by the Surgeon General. Public Health Report, 53:2121-30. 1939 With W. S. Murray and A. M. Cloudman. The genetics of non- epithelial tumor formation in mice. Am. i. Cancer, 36:431-50. With W. S. Murray. Chromosomal and extrachromosomal influ- ence in relation to the incidence of mammary tumors in mice. Am. J. Cancer, 37: 536-52. Civilization against Cancer. 150 pp. New York, Farrar & Rinehart, Inc. Some contributions of the laboratory rodents to our understanding of human biology. Am. Nat., 73:127-38. With W. S. Murray and A. M. Cloudman. The genetics of non- epithelial tumor formation in mice. Am. Nat., 73:467-69. With G. W. Woolley and E. Fekete. Mammary tumor development in mice ovariectomized at birth. Proc. Natl. Acad. Sci., 25:277- 79. Hybridization and tumor formation in mice. Sci., 25:452-55. 1940 Cancer control: early is the word. Of Columbia, 9:97-98. Proc. Natl. Acad. Medical Annals of the District Hospitals and cancer. Hospitals, 14:109-10. Deadly disease number 3cancer. Hygeia, 18:316. Criteria for genetic susceptibility to tumor formation in mice. Acta Unio Internationales Contra Cancrum, 5:15-24. With J. Pearsons. The results of a "functional test" in a strain of mice (C57 black) with a low breast tumor incidence. Am. I. Cancer, 38: 224-33. With G. W. Woolley and E. Fekete. Differences between high and

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CLARENCE COOK LITTLE 259 low breast tumor strains of mice when ovariectomized at birth. Proc. Soc. Exp. Biol. Med., 45:796-98. 1941 Indications of progress in cancer control through education. Bull. Am. Soc. Control Cancer, 23:2-3. in. . . ~ The genetics of spontaneous tumor formation. In: Biology of the Laboratory Mouse, ed. by G. D. Snell, pp. 248-78. New York, McGraw-Hill Book Co. ne genetics ot tumor transplantation. In: Biology of the Labora- tory Mouse, ed. by G. D. Snell, pp. 57-61. New York, McGraw- Hill Book Co. Value of research with animals. Quarterly Review of New York City Cancer Commission, ~uly-October, pp. 57-61. A review of progress in the study of the genetics of spontaneous tumor incidence. I. Natl. Cancer Inst., 1:727-36. Program for research on the biology of human cancer. i. Natl. Cancer Inst., 2: 133-37. With G. W. Woolley and E. Fekete. Effect of castration in the dilute brown strain of mice. Endocrinology, 28:341-43. With G. W. Woolley and L. W. Law. Occurrence in whole blood of material influencing the incidence of mammary carcinoma in mice. Cancer Res., 1: 955-56. With E. Fekete and A. M. Cloudman. Some effects of the gene wv (dominant spotting) in mice. Proc. Natl. Acad. Sci., 27: 114-17. With E. Fekete and G. W. Woolley. Histological changes following ovariectomy in mice. I. dba High tumor strain. J. Exp. Med., 74:1-8. Value of research with animals. 24:7-10. With E. Fekete. Observations on the mammary tumor incidence in mice born from transferred ova. Cancer Res., 2:525-30. With i. M. Spangler and l. M. Murray. Genetics of the suscepti- bility of mice to a transplantable melanoma. l. Natl. Cancer Inst., 3: 123-30. 1942 Bull. Am. Soc. Control Cancer,

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260 BIOGRAPHICAL MEMOIRS 1943 Cancer research. Bull. Am. Soc. Control Cancer, 25:113-15. With G. W. Woolley and L. W. Law. Increase in mammary car- cinoma incidence following inoculations of whole blood. Proc. Natl. Acad. Sci., 29:22-24. With G. W. Woolley and E. Fekete. Gonadectomy and adrenal neoplasms. Science, 97:291. 1944 Facing the challenge of a new era. Hospitals, 18:23-25. Editor. Cancer, A Study for Laymen. New York, Farrar 8c Rine- hart, Inc. 122 pp. Parental influence on incidence of cancer. i. Am. Med. Assoc., 125:93-97. Cancer prevention clinic. Hospitals, 18:29. 1945 With H. McDonald. Abnormalities of the mammae in the house mouse. J. Hered., 36:285-88. Don't neglect cancer. Mississippi Doctor, 22: 191. With G. W. Woolley. in gonadectomized female mice of the extreme dilution strain: I. Observations on the adrenal cortex. Cancer Res., 5:193-202. With G. W. Woolley. The incidence of adrenal cortical carcinoma in gonadectomized female mice of the extreme dilution strain: II. Observations on the accessory sex organs. Cancer Res., 5: 203-10. With G. W. Woolley. The incidence of adrenal cortical carcinoma in gonadectomized male mice of the extreme dilution strain. Cancer Res., 5:211-19. With E. Fekete. Histological study of adrenal cortical tumors in gonadectomized mice of the ce strain. Cancer Res., 5:220-26. With G. W. Woolley. The incidence of adrenal cortical carcinoma in gonadectomized female mice of the extreme dilution strain: III. Observations on adrenal glands and accessory sex organs in mice 13 to 24 months of age. Cancer Res., 5:321-27. With G. W. Woolley. The incidence of adrenal cortical carcinoma in male mice of the extreme dilution strain over one year of age. Cancer Res., 5: 506-10. The incidence of adrenal cortical carcinoma

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C L A R E N C E C O O K L I T T L E 261 With E. M. Vicari. "Lipid-steroid" fractions of mouse adrenal lipids. Proc. Soc. Exp. Biol. Med., 58: 59-60. 1946 Some aspects of cancer research. Alexander Blain Hospital Bul- letin, 5:1-7. Parental influence of mammary tumor incidence. 31. Surgery, 19: 25- With G. W. Woolley. Transplantation of an adrenal cortical car- cinoma. Cancer Res., 6:712-17. With G. W. Woolley. Prevention of adrenal cortical carcinoma by diethylstilbestrol. Proc. Natl. Acad. Sci., 32:239-40. 1947 With H. J. Muller and L. H. Snyder. Genetics, Medicine and Man. Ithaca, Cornell University Press. 158 pp. The genetics of cancer in mice. Biological Review, 22:315-43. With K. P. Hummel. A reverse mutation to a "remote" allele in the house mouse. Proc. Natl. Acad. Sci., 33:42-43. lg48 Halsey Joseph Bagg. Anatomical Record, 100: 397. Genetics in cocker spaniels. I. Hered., 39:181-85. 1949 Biological research in cancer. 52:7-12. With K. P. Hummel. Studies on the mouse mammary tumor agent. I. The agent in blood and other tissues in relation to the physio- logic or endocrine state of the donor. Cancer Res., 9: 129-34. With K. P. Hummel. Studies on the mouse mammary tumor agent. II. The neutralization of the agent by placenta. Cancer Res., 9: 135-36. With K. P. Hummel. Studies on the mouse mammary tumor agent. III. Survival and propagation of the agent in transplanted tumors and in hosts that grew these tumors in their tissues. Cancer Res., 9: 137-38. Chicago Medical Society Bulletin, 1951 fames B. Murphy, 1884-1950. Cancer Res., 11:296.

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262 BIOGRAPHICAL MEMOIRS Genetics in cancer. American {ournal of Obstetrics and Gynecol- ogy (Supplement), 61A:64-68. Genetics and the cancer problem. In: Genetics in the 20th Century, ed. by L. C. Dunn, pp. 431-72. New York, Macmillan Inc. With K. P. Hummel, M. Eddy and B. Rupple. Young produced from ovaries subjected to endocrine imbalance. Proc. Natl. Acad. Sci., 37: 666-69. 1952 With G. W. Woolley and M. M. Dickie. Adrenal tumors and other pathological changes in reciprocal crosses in mice. I. Strain DBA x strain CE and the reciprocal. Cancer Res., 12:142-52. With E. Fekete and F. L. Richardson. The influence of blockage of the nipples on the occurrence of hyperplastic nodules in the mammary glands of C3H mice. Cancer Res., 12:219-21. 1953 With G. W. Woolley and M. M. Dickie. Adrenal tumors and other pathological changes in reciprocal crosses in mice. II. An in- troduction to results of four reciprocal crosses. Cancer Res., 13:231-45. 1954 Genetics, Biological Ind ivid uality, and Cancer. University Press. 115 pp. With L. C. Stevens. Spontaneous testicular teratomas in an inbred strain of mice. Proc. Natl. Acad. Sci., 40:1080-87. Stanford, Stanford 1957 The Inheritance of Coat Color in Dogs. Ithaca, Comstock Pub- lishing Associates. 194 pp. The problem of cancer. In: Proceedings of the 3d National Cancer Conference (1956), pp. 469-72. Philadelphia, J. B. Lippincott Co. Four-ears, a recessive mutation in the cat. J. Hered., 48:57. The yellow Siamese cat. i. Hered., 48:57-58. 1958 Biological aspects of cancer research. I. Natl. Cancer Inst., 20: 441-64.

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CLARENCE COOK LITTLE Coat color genes in rodents and carnivores. Biology, 33: 103-37. 1959 263 Quarterly Review of Genetics of neoplasia. In: Physiopathology of Cancer, 2d ea., ed. by F. Hamburger, pp. 127-51. New York, Paul B. Hoeber, Inc. With K. P. Hummel. Comparison of the virulence of the mam- mary tumor agent from four strains of mice. I. Natl. Cancer Inst., 23:813-21. Francisco Duran-Reynals, bacteriologist. 1961 Science, 129:881-82. Some phases of the problem of smoking and lung cancer. Neal England Journal of Medicine, 264:1241-45. 1963 With K. P. Hummel. Comparative virulence of the mammary tumor agent from different sources; qualitative and quantitative differences. i. Natl. Cancer Inst., 30:593-604. John Joseph Bittner, 1904-1961. Oncologia, 16:354-56. 1964 The relation of age to the incidence of cancer of certain sites. Proc. Natl. Acad. Sci., 52:865-69. 1965 Trends in reported incidence of cancer by age in Connecticut and in New York State (1935-1960~. Proc. Natl. Acad. Sci., 54: 1779-85. 1967 With W. S. Murray. Genetic studies of carcinogenesis in mice. I. Natl. Cancer Inst., 38:639-56. 1969 With W. S. Murray. Reproductive effectiveness in crosses between five inbred strains of mice. J. Natl. Cancer Inst., 42:219-25.