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THOMAS FRANCIS, JR. July 15,1900-October 1,1969 BY JOHN R. PAUL 38 THOMAS FRANCIS, JR., was born in Gas City, Indiana, on July 15, 1900, the son of Thomas and Elizabeth Anne (Cadogan) Francis. His father had emigrated from Wales shortly before Thomas, {r., came into the world. He was the third of four children, but the first to be born in this country. Thomas Francis, Sr., had studied for the ministry as a young mans but had decided later to loin his father In the tin mills of South Wales. He had married Elizabeth Anne Cadogan, a grad- . . . . . . . . . . . . ~ . . . uate of a Salvation Army Trainings, School in London. It is said that she kept "her Salvation Army ideals" throughout her entire life. At least she strove to do her part in supplying a firm religious background to her brood of four children. . In 1897 the Francis family had been persuaded to visit Amer- ~ca. Their destination was a small colony of Welsh families which had settled in and about Gas City, Indiana. For a while this venture was considered to be temporary, but when the family moved to New Castle, Pennsylvania, and Mr. Francis be- came associated with the steel mills of that town, it became permanent. After Thomas Francis, Sr.'s, retirement from the steel mills he turned again to religious ideals and became or- ~ Prior to his death, the author asked Dr. Dorothy M. Horstmann of the Yale School of Medicine to make certain revisions in this memoir. The final version of the memoir owes a great deal to Dr. Horstmann's careful and constructive review, as well as to the faithfulness with which she adhered to the author's style. ~7

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58 BIOGRAPHICAL ME M OIRS dained as a lay minister. Henceforth he was known as the Reverend Thomas Francis. For several years he preached at a small New Castle church. Both parents had very definite ideas about the home life of the Francis family: what it should be and how the children were to act. There were strict rules of behavior, and yet, in spite or because of them, the family life was a happy one. As a boy, Tommy led the normal existence of a lad in a small town en- vironment in which his natural inclinations included fishing and baseball. At the local high school he became quite active in dramatics, which, according to his sister, were usually of the Shakespearean variety. With regard to the rest of Tommy's immediate family, I shall not dwell, although they all enjoyed successful lives. His younger brother, Herbert, graduated in medicine from Yale. The bulk of Herbert's professional career was spent at the School of Medicine, Vanderbilt University, as professor and chairman of the roentgenology department and also as a consultant to the Institute of Nuclear Studies at Oak Ridge, Tennessee. With high school over, where all records maintain that Tommy was an able student, he attended Allegheny College at Meadville, Pennsylvania, and received the B.S. degree in 1921. He entered medical school the following fall. I am not aware of the reason why he made the decision to study medicine but he told me often about his choice of a medical school. In this he was influenced by a brother-in-law (a successful surgeon, Dr. Edgar R. McGuire of Buffalo, New York), whose views he had sought during his last years at college. He was advised to con- sider seriously the idea of applying for admission at the re- juvenated Yale University School of Medicine, which had been completely overhauled by Yale's new President, James R. Angell, who had recently come from the University of Michigan, and by the new Dean of the Medical School, Dr. Milton C. Winternitz, who was also a newcomer at Yale from Johns Hopkins.

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THOMAS FRANCIS, JR. 59 Although the Yale medical school was a venerable school of medicine as far as this country was concerned, having been founded jointly by the Connecticut State Medical Society and Yale College in 1810, it had never achieved its hoped for goals during the nineteenth and early twentieth centuries. Indeed, prior to World War I, it was definitely a second-rate school with only a handful of students. And yet, oddly enough, in 1915 it had on its faculty an unusually distinguished group of men: Yandell Henderson, as professor of physiology, and Lafayette Mendel, of vitamin fame, in biochemistry, both members of the National Academy of Sciences; and two very able and wise clinicians, George Blumer and Wilder Tileston, in internal medicine, both members of the Association of American Physi- clans. . But luckily the school made a sudden rightabout-face when in 1917 Winternitz arrived from Baltimore to assume the posi- tion of chairman of the Department of Pathology. He had previously been an associate professor of pathology at the Johns Hopkins medical school under that dean of pathologists, med- ical educators, and medical historians, Dr. William H. Welch. Dr. Welch had been a loyal graduate of Yale College and his hope was to do something along the lines of a salvage operation for the Yale School of Medicine. Winternitz was an able emissary to perform this duty. His move to Yale had come just at the time when the medical schools of this country were undergoing a state of ferment. The cause of this was the recent issuance, and the recognition of the worth, of the Abraham Flexner Report on Medical Education in the United States and Canada, which introduced a timely reform that was to go into sharp reverse within the next fifty years. Flexner's report was beginning to have its effect in 1917 and Winternitz was quick to take ad- vantage of this. The recommendations concerned, in part, the introduction of the full-time system into the clinical depart- ments of the medical schools of North Americaan idea that

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60 BIOGRAPHICAL MEMOIRS heretofore had been foreign to the rank and file of American physicians, academic or otherwise. Within two years of Winternitz's coming to Yale, the medical faculty, sensing that here was no ordinary professor of path- ology, elected him dean. His plan for Yale was modeled to a certain extent along the lines that made the Johns Hopkins School of Medicine great, that is, close personal contact between scholars and carefully picked students, and a devotion to re- search. So Winternitz, having made his decisions, went about his first task, which was that of gathering together the best young medical scientists and physicians that he could lay his hands on to fill the recently created full-time professorships in the clinical departments: Dr. Francis G. Blake, John P. Peters, and William T. Stadie from the Hospital of the Rockefeller Institute in internal medicine, all three of whom were sub- sequently to become members of the National Academy of Sciences; and Dr. Edwards A. Park in pediatrics. It was at this stage, in 1921, coincident with Dr. Blake's ar- rival at the school as chairman of the Department of Internal Medicine, that the young Francis, having submitted his appli- cation, was accepted, and entered the newly rejuvenated Yale University School of Medicine as a first-year student. He was tak- ing a chance not to have chosen one of the established and better known medical schools of this country. But, as it turned out, it was a chance worth taking. The reason for dwelling so long in this memoir on his academic background is that I am convinced that the training the young Thomas Francis received at Yale opened up a vista of new paths and new opportunities which he eagerly followed. All accounts testify that he was a fun-loving, attractive, and able student, quick to learn and quick to appreciate the idea that the Yale school was supposed to do something out of the ordinaryand to act as a spearhead in a movement of reform

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THOMAS FRANCIS, JR. 61 in medical education for the nation and for Yale University. Most of the members of the clinical faculties, especially those in internal medicine and pediatrics, whose combined members in the 1920s could not have amounted to more than fifteen or eighteen, had put their hearts and souls into making the new scheme work. They were determined to put the Yale school on the map and to establish beyond peradventure that the organiza- tion of the clinical departments on a full-time basis was not a theoretical pipe dream. The young Thomas Francis became keenly aware of the Intimate attention that was being bestowed on this first small group of medical students who had been admitted under the new regime. He soon fell under the spell of the newly appointed faculty members, who besides being clinicians were inspiring and high-minded teacher: men such as Francis G. Blake ~ and lames D. Trask in medicine, and Edwards A. Park and Grover F. Powers in pediatrics. Dr. Blake was especially quick to recog- nize Francis's ability and his early grasp of what the school was supposed to do. As a result, a mutual respect developed that lasted throughout their lives. With Dr. Blake he had almost a filial rapport. He admired Francis Blake as an astute diagnostician, a wise teacher, a physician and medical scientist of complete integrity, and an able clinical investigator. Besides, Blake had something akin to an epidemiological instinct long before that science had re- ceived the attention in this country that it deserved. This last characteristic accounted for Blake's being chosen as the first president to head the Army Epidemiological Board (AEB) during the years of World War II and for some years afterward. ~ The fells instructors in the Department of Medicine in the Yale University School of Medicine of the 1920s who are living today all testify to this estimation of his character. , See memoir of Francis G. Blake, by Dr. J. R. Panel, in National Academy of Sciences, Biographical Memoirs, 28 (1954):1-29.

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62 B I O G R A P H I C A L M E M O I R S Some of these qualities must have rubbed off on the young medical student who was eventually to become Dr. Blake's suc- cessor as president of the AEB Esubsequently the AFEB (Armed Forces Epidemiological Board)] in the years 1958-1960. . . ~ ~ When Dr. Francis graduated as an M.D. in 1925, he was Immediately appointed as an intern on the medical service of the New Haven Hospital, the next year as resident, and the next as an instructor in Blake's Department of Internal Medi- cine. This was a prime example of the apprenticeship type of ~ns~rucr~on In which the professor did not have to preach but resorted instead to imparting the principles of clinical medicine by personal example. As a result, the young Dr. Francis was inspired to set his sights to emulate Dr. Blake, who in turn recognized that his pupil, having fulfilled his post of house officer and instructor admirably, had also begun to show signs of promise as a clinical investigator. Blake's early estimate of Francis's talents was not far wrong, for sixteen years later Francis was to become the president of the American Society for Clin- ical Investigation. In any event, Blake decided that here was no ordinary young physicianindeed, Thomas Francis was one who might go far. So he advised him to prepare himself further by a period of training at the best contemporary institution that was available for this kind of instruction, namely, the Hospital of the Rocke- feller Institute. Blake had no hesitancy in recommending Dr. Francis to Rufus I. Cole, the director of this hospital, as a prom- ising candidate. Francis was a young man who possessed all the talents of an able house officer and the qualifications of a budding research worker (assets which were highly sought after by Dr. Cole in any candidate he was to take on as a junior member of his staff) . This sophisticated center of learning and research was a far cry from New Castle, Pennsylvania. Had Francis pursued this course of in-service training to its obvious end, it should have led him straight down the path

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THOMAS FRANCIS, JR. 63 of an academic career in internal medicineto an assistant, then associate, and eventually a full professorship at one of the full-time medical schools in this country. But other career goals eventually proved more attractive to him. Among the group which Dr. Cole had assembled on the Rockefeller hospital staff at this time were included Drs. Thomas M. Rivers, William T. Tillett, Oswald T. Avery, Donald D. Van Slyke, Alfred E. Cohn, Homer F. Swift, and several others whose names were to rank high during the 1930san era which is understandably considered by some as the age of the flowering of American Medicinespelled with a capital M. It was during this period that the young Thomas Francis began to gain a feeling of confidence that he had arrived as a person to be reckoned with in the field of full-time clinical investigation. Besides his qualifications as an investigator, his clinical abilities as a young physician also came to the fore on the the wards of the Rockefeller hospital. He often told me that he must have been appreciated as "a doctor" at this time. Among his prominent "private patients" were members of the Rockefeller family, and for a time he almost rated as their private physician. Indeed, during the first half of his lone and distinguished ~ 1_ ~ ~ . . ~ c~ ~ _ career, ne ala not relinquish the hope that he might be con- sidered as a suitable candidate for a position as chairman of the Department of Medicine in one or another of the country's leading medical schools. This hope was not based on the fact that he possessed a knowledge of medicine that was of en- cyclopedic nature, but he felt the important thing was that he had acquired from his parents and his respected teachersDrs. Blake and Colethe altruistic principles of a physician, as well as the ideals of clinical medicine and, incidentally, of clinical investigationand this was enough. Talents which Dr. Francis had developed at this time were those that had to do with both clinical and experimental medicine in infectious disease, micro-

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64 BIOGRAPHICAL ME M OIRS biology, and epidemiology. He could have filled an academic position in any of these various fields, as well as a professorship in internal medicine. On arrival at the Hospital of the Rockefeller Institute, Dr. Francis pursued the line of work that he had started under Dr. Blake at Yale. His interest had been aroused by studies which had to do with the various types of the pneumococcus, both rough and smooth varieties, and with the respiratory diseases including lobar pneumonia, a subject of great interest in that pre-antibiotic age. In an article written immediately after Dr. Francis's death, Colin M. MacLeod said: "On coming to Avery's laboratory, Francis and William Tillett worked together on cutaneous and serological reactions to products of pneumococcus, particularly the specific capsular polysaccharides and the 'C' or somatic carbohydrate, now known to be a constituent of the bacterial cell wall. Over the three- ^. ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ^_ _ ~ ~ ~ ~ _ ~ ~ ~ _ ~ _ A ~ year period of their collaboration two remarkable findings came forth. "The first of these was that there occurs in the blood of patients with many acute infections a new substance, not an antibody in the usual sense, which reacts specifically with the 'C' carbohydrate of pneumococcus to give a precipitation re- action. During recovery from the disease the 'C-reactive pro- tein,' as it came to be known, diminishes in amount and within a few days disappears entirely. This is an enigmatic reaction whose function in man and animals is still unknown but which provides a useful clinical test to measure the activity of a variety of infectious processes, for example the activity of the inflamma- tory process in rheumatic fever. "Francis and Tillett also discovered that minute amounts of specific capsular polysaccharides of pneumococcus injected in- tracutaneously in man cause the development of specific anti- bodies and that the antibodies are protective.... "While Francis was in Avery's laboratory, Dubos and Avery

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THOMAS FRANCIS, JR. 65 had developed their famous studies on an induced enzyme obtained from a soil bacterium which specifically hydrolyzes the capsular polysaccharide of pneumococcus Type III whether the latter is in solution or attached to the living, virulent pneumococcus." ~ Dr. MacLeod went on to say: "Francis, with Terrell, de- vised methods for producing Type III pneumonia in monkeys and published meticulous studies of its clinical course. In collaboration with Dubos and Avery they then went on to demonstrate in this experimental disease of primates, which simulates pneumococcal pneumonia in man, that the S III enzyme has striking curative properties. Unfortunately, test of the ~~ ~;~ ~~ ~ ., t11C Lll~l-~CULlC erect In man was never carried out.'' ~ , ~ . . .. ~ . . Con nuance or tins line ot Investigation was due to Dr. Francis's departure from the pneumonia service when he entered upon his work on influenza. But Francis must have derived not a little satisfaction from his early work at the Rockefeller hospital, for in recounting the memory of it some forty years later in his address entitled "Moments in Medical Virology," presented at the First International Congress for Virology in Helsinki, Finland, he recalled events that had occurred while he had been working enthusiastically on the transformation of pneumococcus types. He said: "So I spent the mornings in the laboratory learning of these phenomena and the afternoons in the library and on the tennis court developing a model of the double fault. Being convinced that the induced change of pneumococcus types in the animal host was a true bill, I began very primitive efforts to obtain transformation in the test tube. (It is worth noting that a healthy air of skepticism surrounded the entire phenomenon that probably some live organisms were persisting in the heated, supposedly, killed preparation.) It became clear that the ~ Colin M. MacLeod, "Thomas Francis, Jr., 1900-1969," Arch. Environmental Health, 21 (1970):226-29.

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66 capsular polysaccharide, with all its divine properties, was not the effective agency. But then it seemed likely that whatever the transforming principle was, it needed special care and I began making extracts be freezing and thawing organisms in BIOGRAPHICAL MEMOIRS , ~ the cold under relatively anaerobic conditions so as to avoid an enzymatic destruction of the principle. One day at noon I thought I was all alone in the lab. I was occupied with the tedious procedure of freezing and thawing. I had put my head down on my arms on the desk. Unexpectedly, a quiet voice said, 'What's the matter, boy?' Startled, I said I hated to see another pneumonia season start with the great time and at- tention required for clinical work; that I thought what was in these flasks was more exciting. Then I received a very sharp lecture from Dr. Avery reminding me that we were physicians; that the major concern of this laboratory was lobar pneumonia and that what was done here was in effect to understand the disease and to lick the pants off the pneumococcusa theme that was developed under Avery and Dubos with the Type III de- capsulating enzyme. This is a true view of Avery's intellectual commitment to the clinical problem. "New lines of effort were freely allowed even if they were not always enthusiastically supported. I found this when I studied transformation of the rough Type III to virulent in rabbits; there was a lot of specificity involved and much work, but it never was published until later (by others).... Things were apparently dormant for 10 years. "Then came the epochal study by Avery, MacLeod and McCarty in 1944.... "Somewhere in these early days I rode on the train from New York to Princeton, New Jersey, with two leaders in virology, Thomas Rivers and Christopher Andrewes, to see a third, Dick Shope. In those days, virology had not yet descended to the level of the common man and I listened, as the privileged young

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100 BIOGRAPHICAL MEMOIRS Control of virus infections. i. Mich. Med. Soc., 46:566. Apparent serological variation within a strain of influenza virus. Proc. Soc. Exp. Biol. Med., 65:143. With G. C. Brown. Studies on the relation of wild rats to polio- myelitis. I. Infect. Diseases, 81:55. With i. E. Salk and J. I. Quilligan, Jr. Experience with vaccination against influenza in the spring of 1947. Am. l. Public Health, 37:1013. The present status of vaccination against influenza. Health, 37:1109. Am. I. Public Mechanisms of infection and immunity in virus diseases of man. Bacteriological Reviews, 11: 147. With G. C. Brown. The neutralization of the mouse-adapted Lansing strain of poliomyelitis virus by the serum of patients and contacts. T. Immunol., 57:1. Respiratory viruses. Annual Review of Microbiology, 1:351. With J. I. Quilligan, in Serological response to intranasal admin- istration of inactive influenza virus in children. I. Clin. Invest., 26:1079. Infectious hepatitis. In: Hand book of Communicable Diseases, 2d ea., ed. by F. H. Top. St. Louis, The C. V. Mosby Company, Medical Publishers. 1948 With G. C. Brown and J. Ainslie. Studies of the distribution of poliomyelitis virus. V. The virus in familial associates of cases. i. Exp. Med., 87:21. Viruses as agents of disease. Oral Surg., Oral Med., Oral Pathol., 1:153. The prevention of virus diseases. Oral Surg., Oral Med., Oral Pathol.; 1: 160. With G. C. Brown. Studies of the distribution of poliomyelitis virus. IV. In rural schools following an epidemic. i. Infect. Diseases, 82: 163. With G. C. Brown and L. R. Penner. Search for extrahuman sources of poliomyelitis virus. J. Am. Med. Assoc., 136:1088. With I. I. Quilligan, fir., and E. Minuse. Homologous and hetero- logous antibody response of infants and children to multiple injections of a single strain of influenza virus. l. Clin. Invest., 27:572.

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THOMAS FRANCIS, JR. 101 With E. Minuse. Influence of saliva upon hemagglutination by influenza virus. Proc. Soc. Exp. Biol. Med., 69:291. Parasitism and disease. In: Bacterial and Mycotic Infections of Man, ed. by R. J. Dubos. Philadelphia, J. B. Lippincott Com- pany. Response of the host to the parasite. In: Bacterial and Mycotic In- fections of Man, ed. by R. J. Dubos. Philadelphia, J. B. Lippin- cott Company. With C. Armstrong, D. Bodian, A. B. Sabin, and l. R. Paul. posed provisional definition of poliomyelitis virus. Science, 108:701. (Committee on Nomenclature of the National Foun- dation for Infantile Paralysis.) 1949 With G. C. Brown and i. D. Ainslie. The incidence of poliomyelitis virus in cases of mild illness during a severe urban epidemic. Am.J.Hyg.,49:194. Immunity in poliomyelitis. Phi Chi Quarterly, October, 1949. (First Annual Dr. Eben I. Carey Memorial Lecture, Omaha.) With G. C. Brown. ~ , , Evaluation of the effect of Darvisul upon in- fection with SK strain of virus in mice. Proc. Soc. Exp. Biol. Med., 70:535. With I. I. Quilligan, fir., and E. Minuse. Resemblance of a strain of swine influenza virus to human A-prime strains. Proc. Soc. Exp. Biol. Med., 71:216. With I. J. Quilligan, fir., and E. Minuse. Reactions to an influenza virus in infants and children. American Journal of Diseases of Childen, 78:295. The family doctor: an epidemiologic concept. I. Am. Med. Assoc., 141:308. Immunization Contra Influenza, Vol. 3. (One of a series of medical articles prepared exclusively for the physicians of Peru by dis- tinguished authorities of the United States.) NVith K. Penttinen. The failure of Merodicein to modify influenza virus infections. i. Immunol., 63:337. 1950 Immunity and vaccination in influenza. In: Handbuch der Virus- forschung, ed. by R. Doerr and C. Hallauer, pp. 66-86. Vienna, Springer-Verlag. II. Erganzungsband.

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102 B I O G R A P H I C A L M E M O I R S With l. J. Quilligan, fir., Richard i. Rowe, et al. The action of Terramycin on the growth of strains of influenza, herpes simplex, and rabies viruses in chick embryos and mice. Ann. N.Y. Acad. Sci., 53:407. With H. B. Kurtz. The relation of herpes virus to the cell nucleus. Yale i. Biol. Med., 22:579. With W. W. Ackermann. Some biochemical aspects of herpes in- fection. Proc. Soc. Exp. Biol. Med., 74:123. The significance of multiple immunological types of influenza virus. Cincinnati Journal of Medicine, 31: 97. With others. An agglutination-inhibition test proposed as a stand- ard of reference in influenza diagnostic studies. I. Immunol., 65:347. (Committee on Standard Serological Procedures in In- fluenza Studies.) Immunology and preservation of the norm. i. Immunol., 65:437. With [. I. Quilligan, fir., and E. Minuse. Identification of another epidemic respiratory disease. Science, 112:495. With J. D. Ainslie and J. L. McCallum. Failure to demonstrate antibody in feces of monkeys vaccinated with poliomyelitis virus, Lansing strain. Proc. Soc. Exp. Biol. Med., 75:699. 1951 With F. M. Davenport. A comparison of the growth curves of adapted and unadapted lines of influenza virus. l. Exp. Med., 93:129. With l. D. Ainslie and P. K. Stumpf. Serum alkaline phosphatase in monkeys and man during poliomyelitis. Am. J. Hyg., 53:58. Immunity in virus diseases. Cornell Veterinarian, 41:190. Plan for the evaluation of vaccination against influenza. Am. J. Public Health, 41:62. With l. D. Ainslie and G. C. Brown. ACTH in experimental polio- myelitis in monkeys and mice. J. Lab. Clin. Med., 38:344. 1952 With G. C. Brown, J. D. Ainslie, A. G. Gilliam, and A. R. Zintek. Studies of the distribution of poliomyelitis virus. VI. In a small community in an epidemic area. Am. I. Hyg., 55:49. Distribution of poliomyelitis virus in the epidemic community. Trans. Assoc. Am. Physicians, 65: 176. Distribution of poliomyelitis virus in a community. In: Polio-

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THOMAS FRANCIS, JR. 103 myelitis, pp. 355-63. Proceedings of the Second International Poliomyelitis Conference. Philadelphia, i. B. Lippincott Com- pany. Developing a philosophy for the Committee on Research and Standards. Am. I. Public Health, 42:85. Significance of antigenic variation of influenza viruses in relation to vaccination in man. Federation Proceedings, 11:808. Parisitism and disease. In: Bacterial and Mycotic Infections of Man, 2d ea., ed. by R. J. Dubos, pp. 68-74. Philadelphia, J. B. Lippincott Company. Response of the host. In: Bacterial and Mycotic Infections of Man, Ed ea., ed. by R. J. Dubos, pp. 98-118. Philadelphia, J. B. Lip- pincott Company. 1953 Research in poliomyelitis at Michigan. Michigan Alumnus Quar- terly Review, February. Influenza: method of Thomas Francis, Jr. In: Current Therapy, ed. by H. F. Conn. Philadelphia, W. B. Saunders Company. With K. E. Jensen. Antigen-antibody precipitates in solid medium with influenza virus. I. Immunol., 70:321. Vaccination against influenza. Bull. World Health Organ., 8:725. Influenza: the newe acquayantance ~sic]. Ann. Internal Med., 39: 203. With L. W. Chu. The interaction in vitro between poliomyelitis virus and nervous tissue. In: Proceedings of the Sixth Inter- national Congress of Microbiology, Rome, Italy, 1953. Vol. 8, p. 162. (A) With A. V. Hennessy, E. Minuse, and F. hi. Davenport. An ex- perience with vaccination against influenza B in 1952 by use of monovalent vaccine. Am. J. Hyg., 58: 165. Correlations in clinical and epidemiological investigation. Am. I. Med. Sci., 226:376. With G. C. Brown and J. D. Ainslie. Poliomyelitis in Hidalgo County, Texas, 1948: poliomyelitis and Cocksackie viruses in privy specimens. Am. J. Hyg., 53: 310. With K. E. Jensen. The antigenic composition of influenza virus measured by antibody-absorption. J. Exp. Med., 98:619. With F. M. Davenport and A. V. Hennessy. Epidemiologic and Am. J. Hyg., 53:310. . .

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104 The teaching of epidemiology. BIOGRAPHICAL MEMOIRS immunologic significance of age distribution of antibody to antigenic variants of influenza virus. i. Exp. NIed., 98:641. 1954 - O 1 a, In: Proceedings of the First World Conference on Med ical Ed ucation, London, 1953. London, Ox- ford University Press. With W. W. Ackermann. isolated animal tissues. Characteristics of viral development in Advances in Virus Research, 1 1:81. With E. Minuse and J. J. Quilligan, Jr. Type C influenza virus. I. Studies of the virus and its distribution; II. Intranasal inocula- tion of human individuals. I. Lab. Clin. Med., 43:31. Evaluation of gamma globulin in prophylaxis of paralytic polio- myelitis in 1953: summary of the Report of the National Ad- visory Committee for Evaluation of Gamma Globulin. I. Am. Med. Assoc., 154: 1086. Immunological and epidemiological problems. Royal Society of Medicine, 47:561. With L. R. Penner and G. C. Brown. Some observations on the ecology of a North American chigger Trombicula (:Eutrombicula) lipovskyana, Wolfenbarger, 1952, in a Tennessee community. journal of the Kansas Entomological Society, 27: 1 13. With G. C. Brown and A. Kandel. Effect of fluoroacetate upon poliomyelitis in monkeys. Proc. Soc. Exp. Biol. NIed., 85:83. With K. W. Cochran and G. C. Brown. Antiviral action of a mold filtrate on experimental poliomyelitis in cynomologus monkeys. Proc. Soc. Exp. Biol. Med., 85:104. The teaching of epidemiology. Journal of Medical Education, 29:15. Proceedings of the 1955 Approach to control of poliomyelitis by immunological methods. Bull. N.Y. Acad. Med., 31:259. With R. F. Korns, R. B. Voight, et al. An Evaluation of the 1954 Poliomyelitis Vaccine Trials; Summary Report. Ann Arbor, Michigan, Poliomyelitis Vaccine Evaluation Center, Uni- versity of Michigan. 50, 63 pp. (Sponsored by the National Foundation for Infantile Paralysis.) Also in Am. J. Public Health, Vol. 45, May, Part II, special issue. With R. F. Korns. Evaluation of 1954 field trial of poliomyelitis vaccine: synopsis of summary report. Am. J. Med. Sci., 229:603.

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THOMAS FRANCIS, JR. 105 Poliomyelitis issue. Univ. Mich. Med. Bull., 21:153-55. Evaluation of the 1954 poliomyelitis vaccine field trial: further studies of results determining the effectiveness of poliomyelitis vaccine (Salk) in preventing paralytic poliomyelitis. J. Am. Med. Assoc., 158: 1266. The current status of the control of influenza. Ann. Internal Med., 43:534. \Vith F. M. Davenport, A. V. Hennessy, and C. H. Stuart-Harris. Epidemiology of influenza: comparative serological observations in England and the United States. Lancet, 2:469-74. Summary and review of poliomyelitis immunization. Ann. N.Y. Acad.Sci.,61:1057. Virus problems in medicine. Illinois Medical journal, 108:257. With A. V. Hennessy and F. At. Davenport. Studies of antibodies to strains of influenza virus in persons of different ages in sera collected in a postepidemic period. J. Immunol., 75:401. Edith D. Bodian, C. Larson, et al. Interim report, Public Health Service Technical Committee on Poliomyelitis Vaccine. I. Am. Med. Assoc., 159: 1444. 1956 With K. W. Cochran. Antiviral action of helenine on experimental poliomyelitis. Proc. Soc. Exp. Biol. Med., 92:230. With I. F. Enders, I. A. Bell, I. H. Dingle, et al. Adenoviruses: group name proposed for new respiratory tract viruses. Science, 124:119. With K. E. Jensen, F. M. Davenport, and A. V. Hennessy. Char- acterization of influenza antibodies by serum absorption. l. Exp. Med., 104: 199. Approaches to the prevention of poliomyelitis. Univ. Mich. Med. Bull., 22:433. With J. Napier and F. NI. Hemphill. Poliomyelitisschutzimpfung. Munchener Medizinische Wochenshrift, 98:1349-55. lg57 Symposium on controlled vaccine field trials. Poliomyelitis. Am. J. Public Health, 47:283. With K. E. Jensen and E. Minuse. Serologic comparisons with lines of influenza virus isolated and serially transferred in different experimental hosts. l. Immunol., 78:356.

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106 BIOGRAPHICAL MEMOIRS Epidemiology and the future of medicine. University of Tennessee Record, Vol. 60, No. 6. With L. Blair, M. Jacobs, et al. The role of the physical therapist in the evaluation studies of the poliomyelitis vaccine- field trials. Physical Therapy Review, 37:437. With F. M. Davenport and A. V. Hennessy. Influence of primary antigenic experience upon the development of a broad immunity to influenza. Trans. Assoc. Am. Physicians, 70:81. Mobilization against influenza. Science, 126: 1267. Vaccination against Asian influenza: basis for recommendations and a preliminary report on efficacy. Members of the Commission on Influenza of the Armed Forces Epidemiological Board, Office of the Commission on Influenza, School of Public Health, Uni- versity of Michigan, Ann Arbor. I. Am. Med. Assoc., 165:2055. With i. A. Napier, R. B. Voight, et al. Evaluation of the 1954 Field Trial of Poliomyelitis Vaccine; Final Report. Ann Arbor, Mich- ~gan, Edwards Brothers, Inc. xxxi + 563 pp. Facts and perspectives of a large-scale field trial. Special Publica- tions of the New York Academy of Sciences, 5:99. 1958 A New Year's fantasy. Univ. Mich. Med. Bull., 24:1. With K. G. Kohlstaedt, M. Moser, et al. Panel discussion on genetic and environmental factors in human hypertension. Circulation, 17: 728, Part II. Immunization. J. Mich. Med. Soc., 57:742. Immunity to virus diseases. In: Symposium on Viruses: Current A dvances with Clinical A pplications, p. 123. Influenza. In: Communicable Diseases: Preventive Medicine in World War II, ed. by E. C. Hoff, Vol. 4, pp. 85-128. Washington, D.C., Department of the Army, Once of the Surgeon General. With D. E. Craig. Contact transmission of poliomyelitis virus among monkeys. Proc. Soc. Exp. Biol. Med., 99:325. Frederick George Novy 1864-1957. Trans. Assoc. Am. Physicians, 71:35. Viral inhibition. In: Poliomyelitis, pp. 361-65. Proceedings of the Fourth International Poliomyelitis Conference. Philadelphia, J. B. Lippincott Company. 1959 Influenza. In: Viral and Rickettsial Infections of i\Ian' ad ea., ed.

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THOMAS FRANCIS, JR. 107 by Thomas M. Rivers and Frank L. Horsfall, {r., pp. 633-72. Philadelphia, J. B. Lippincott Company. With F. H. Epstein, W. D. Block, and E. A. Hand. Familial hyper- cholesterolemia, xanthomatosis and coronary heart disease. American journal of Medicine, 26: 39. Adventures in preventive medicine: the Founder's Day address Allegheny College Bulletin, June. Influenza. Med. Clin. N. Am., 43:1309. Serological variation. In: Animal Viruses, Vol. 3 of The Viruses: Biochemical, Biological, and Biophysical Properties, ed. by F. M. Burnet and W. M. Stanley, pp. 251-73. New York, Academic Press, Inc. The epidemiological approach to human ecology. Sci., 237:677. Am. J. Med. 1960 Research in preventive medicine. .T- Am. NIed. Assoc., 172:993. Preventive medicine in 1985 and a re-emphasis on the preservation of health. What's New, 220:26. On the doctrine of original antigenic sin. ican Philosophical Society, 104:572. 1961 Proceedings of the Amer- Influenza in perspective. Am. Rev. Resp. Diseases, 83:98. Biological aspects of environment. Industrial Medicine and Sur- gery, 30:374. Aspects of the Tecumseh study. Public Health Reports, 76:963. With W. D. Peterson and F. M. Davenport. A study in vitro of components in the transmission cycle of swine influenza virus. J. Exp. Med., 114: 1023. Problems of acute respiratory disease. Yale l. Biol. Med., 34:91, 1961-62. 1962 With G. C. Brown. Incidence of heterologous antibodies in virus- confirmed cases of poliomyelitis. New England Journal of Medicine, 266:642. With B. I. Ned, W. W. Ackermann, and F. H. Epstein. Inhibition of vaccinial hemagglutinins by sera of patients with coronary heart disease and other chronic illnesses. Circulation Research, 10:836.

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108 With E. Minuse, P. W. Willis III, and F. M. Davenport. An at- tempt to demonstrate viremia in cases of Asian influenza. l. Lab. Clin. Med., 59:1016. With B. I. Neff, G. L. Brady, and F. H. Epstein. Serologic and pathologic changes in rats on atherogenic diets. Journal of Atherosclerosis Research, 2:306. BIOGRAPHICAL MEMOIRS 1963 Epidemic influenza. Am. Rev. Resp. Diseases, 88:148. 1964 With A. V. Hennessy, F. M. Davenport, R. J. Horton, and J. A. Napier. Asian influenza: occurrence and recurrence, a com- munity and family study. Military Medicine, 129:38. With F. M. Davenport, A. V. Hennessy, l. Drescher, and J. Mulder. Further observations on the relevance of serologic recapitula- tions of human infection with influenza viruses. I. Exp. Med., 120:1087. Ernest William Goodpasture (1886-1960~. In: American Philo- sophical Society Yearbook 1964, pp. 111-20. Philadelphia, Amer- ican Philosophical Society. 1965 A portrait of Henry F. Vaughan. Center Journal, 31: 100. With H. F. Maassab. Influenza virus. In: Viral and Rickettsial Infections of Man, 4th ea., ed. by F. L. Horsfall and I. Tamm, pp. 689-740. Philadelphia, I. B. Lippincott Company. In honor of Richard E. Shope. In: Perspectives in Virology IV, ed. by M. Pollard. New York, Hoeber Medical Division, Harper & Rowe, Publishers. With F. H. Epstein, N. S. Hayner, et al. Prevalence of chronic diseases and distribution of selected physiologic variables in a total community, Tecumseh, Michigan. Epidemiology, 81:307. Genetics and epidemiology. In: Genetics and the Epid emiology of Chronic Diseases, ed. by I. V. Neel, M. W. Shaw, and W. I. Schull. Public Health Service publication 1163. Washington, U.S. Govt. Print. Off. With F. H. Epstein. Tecumseh, Michigan. Quart., 43:333. University of Michigan Medical American Journal of Milbank Mem. Fund

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THOMAS FRANCIS, JR. 109 With F. H. Epstein, L. D. Ostrander, Jr., B. C. Johnson, M. W. Payne, N. S. Hayner, and I. B. Keller. Epidemiological studies of cardiovascular disease in a total community. Ann. Internal Med.,62:1170. Standards for research in new drug testing. In: Proceedings of the Fourth International Congress of the International Federation for Hygiene and Preventive Medicine, 2d ed. Vienna, May 1965. Vienna, Wiener Medizinishe Akademie. \Vith G. C. Brown, H. F. Maassab, and I. A. Veronelli. Detection of rubella antibodies in human serum by the indirect fluorescent antibody technique. Archiv fur die Gesampte Virusforschung, 16:459. With L. D. Ostrander, N. S. Hayner, et al. The relationship of cardiovascular disease to hyperglycemia. Ann. Internal Med., 62:1 188. Standards required in vaccine field trials. In: Proceedings of the Cholera Research Symposium, Honolulu, January 24-29, 1965, publication 1328, pp. 352-54. Washington, U.S. Govt. Print. Off. With N. S. Hayner, M. O. Kjelsberg, and F. H. Epstein. Carbo- hydrate tolerance and diabetes in a total community, Tecumseh, Michigan. Diabetes, 14:413. With N. S. Ling and T. Krasteff. Transcholesterin, a cholesterol- binding globulin: serological demonstration of a specific inter- action between cholesterol and serum globulin. Proceedings of the National Academy of Sciences, 53:1061. With E. Minuse, I. L. McQueen, and F. A. Davenport. Studies of antibodies to 1956 and 1963 equine influenza viruses in horses and man. l. Immunol., 94:563. 1966 The polyvalent vaccine: reasons for inclusion of earlier virus pro- totypes and contemporary virus strains into current and future vaccines. (Read before Division of Biologics Standards Con- ference on Formulation of Influenza Virus Vaccines. National Institutes of Health, October 1966.) 1967 With L. D. Ostrander, Jr., B. I. Ned, W. D. Block, et al. Hyper- glycemia and hypertriglyceridemia among persons with coronary heart disease. Ann. Internal Med., 67:34.

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110 BIOGRAPHICAL MEMOIRS Summary. In: Working Conference on Smallpox Rapporteurs' Re- ports, pp. 23-26. Sponsored by the U.S.-Japan Cooperative Medical Science Program, Once of International Research, Na- tional Institutes of Health. Epidemic influenza: immunization and control. Med. Clin. N. Am., 51:781. Immunization of selected population groups against influenza. Archives of Environmental Health, 14:747. With T. O. Anderson, F. W. Denny, et al. Epidemiologic Studies for Vaccine Development. U.S. Department of Commerce, PB 176 814, National Bureau of Standards Institute of Applied Tech- nology. 1968 Transcholesterin titers and their biological significance in experi- mental atherogenesis in rats. Proc. Soc. Exp. Biol. Med., 128: 197. Experience with vaccines: general comments. In: Conference on Cell Cultures for Virus Vaccine Production, Bethesda, Maryland, November 1967. National Cancer Institute Monograph 29. lg69 Faktoren der Immunitat gegen respiratorische Infekte. Deutsche MedizinischeWochenschrift, 94:355. With F. M. Davenport, E. Minuse, and A. V. Hennessy. Interpreta- tion of influenza antibody patterns of man. Bull. World Health Organ., 41 :453. zenith A. S. Monto, F. M. Davenport, and J. A. Napier. EFect of vaccination of a school-age population upon the course of an A2/Hong Kong influenza epidemic. Bull. World Health Organ., 41:537. With H. F. Maassab, F. M. Davenport, et al. Laboratory and clin- ical characteristics of attenuated strains of influenza virus. Bull. World Health Organ., 41:589. Moments in medical virology. In: International Virology, 1, ed. by J. L. Melnick, p. 224. Proceedings of the First International Con- gress for Virology. Basel, Switzerland, S. Karger, A.G.