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Biographical Memoirs: Volume 50 (1979)

Chapter: Frank Lappin Horsfall, Jr.

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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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Suggested Citation:"Frank Lappin Horsfall, Jr.." National Academy of Sciences. 1979. Biographical Memoirs: Volume 50. Washington, DC: The National Academies Press. doi: 10.17226/573.
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FRANK LAPPIN HORSFALL December 74, 1906-February 19, 1971 BY GEORGE K. HIRST JR. FRANK L. HORSFALL, JR. was a clinician and a virologist whose influential leadership came primarily through his perceptive scientific experimentation, both in the laboratory and in the clinic, and also through his vast administrative skill. He was born December 14, 1906 in Seattle, Washington, where he spent all his formative years until he was twenty-one. His father, a native Vermonter, was a prominent surgeon who maintained a large house on Capitol Hill, and Frank, the first of four children, was a high-spirited youth whose interests led him into a wide range of activities. By the time he entered high school, he had decided to become an engineer, and he spent afternoons and evenings with a friend rigging up the family Victrola for radio reception. In the course of his four years at high school, he participated actively in the student council, the boys' athletic association, the glee club, and the radio press association. He was valedictorian of his class. During four years of college at the University of Washington he lived in a fraternity house, and during the early part of this experience he was uncharacteristically erratic in the pursuit of his studies. It was during this period that he went out for crew, a major sport at Washington, and made the junior varsity. One of his outstanding characteristics was a tendency to throw him- self headlong into every new activity, and it is reported that he 233

234 BIOGRAPHICAL MEMOIRS became a passionate oarsman, spending every moment of his spare time rowing or hanging around the boathouse. However, many years later, although he kept his oar on the wall, he com- pletely disavowed any interest in rowing and for that matter in all other forms of athletics, either as a participant or as a spectator. Midway through his college course he gave up the idea of becoming an engineer and decided to enter the medical pro- fession. This involved some heroic scrambling to complete the course-work requirements, but in 1927 he followed in his father's footsteps by entering McGill University, in Montreal, Canada, and graduated in 1932, at which time he received the Holmes Gold Medal for having attained the highest scholastic record in his class. After receiving his medical degree, he spent a year as a house officer in pathology at the Peter Bent Brigham Hospital in Boston. This was a common preliminary to a postgraduate edu- cation in surgery. It was during this year that he discovered that he was exquisitely sensitive to formaldehyde, a fact which markedly influenced later career decisions. He responded characteristically to this disability by embark- ing at once on an extensive study of formaldehyde sensitivity in experimental animals and coupled this with a long series of experiments on himself. The result was two substantial papers on the subject, in which for the first time Horsfall was the sole or the senior author, and in them he acknowledged the assis- tance and advice of both H. Zinsser and S. B. Wolbach. This was the beginning of Horsfall's informal training in immunology, training which was to continue after another year at the Rocke- feller Institute. He returned to Montreal for a year's internship in medicine at the Royal Victoria Hospital and then signed up for a year in surgery, but shortly after starting the latter position he found that it was incompatible with his formaldehyde sensitivity, ant!

FRAN K LAPPIN HORSFALL, JR. 235 he promptly resigned. Immediately thereafter, in the fall of 1934, he went to the Rockefeller Institute in New York City, where he was to remain with only minor interruption for the next twenty-five years. On giving up a surgical career, for which he was eminently qualified, he showed no outward evidence of regret and quickly plunged off in another direction, which involved him in clinical research coupled with basic research. Horsfall came to New York at a time when the Rockefeller Institute Hospital was at a peak of its reputation in the academic medical world. Although it was a very small unit, it had a very big reputation for pioneering in medical research. The staff members were both clinical and nonclinical, and there was a well-developed mystique among them concerning the catalytic effect which clinical contact had on basic research. A majority of the young people there were like Horsfall in that they came from purely medical backgrounds and were to spend formative postdoctoral years in this very stimulating environment learning, in an informal manner, the basic disci- plines such as bacteriology, virology, immunology, and physi- ology. Through these young people the Hospital provided excellent medical care, and at the time Horsfall was added to the staff the pneumonia service had nearly completed a large and successful series of cases in which type I pneumonia had been treated with specific antipneumococcal horse serum. These results had aroused widespread interest, and such sera were . . coming Into general use. In addition to the time spent on clinical responsibilities, all of the younger staff members were engaged in some basic re- search project. Those on the pneumonia service often worked on model infections in mice. Among the older staff members there were some who did no clinical work at all, and the most outstanding of these was Oswald T. Avery. The exceptional thing about the Avery school was that its immediate goals were so great and still far removed from any clinical application. His

236 BIOGRAPHICAL MEMOIRS very solid intellectual outlook set the tone for the whole depart- ment. On entering this mixed atmosphere of clinical and academic science, Horsfall clearly and consistently showed his marked preference for those activities for which there appeared to be obvious relevant application to clinical work. Horsfall's em- phasis on medical application would be demonstrated again and again throughout his career, even when he was not taking care of patients. He tackled his clinical responsibilities with en- thusiasm. He was an eager therapist, and there are apocryphal reports about the strong restraints required to prevent him from testing in patients the enzyme capable of splitting the type III capsular carbohydrate, which had been developed by O. T. Avery and Rene Dubos. He was also an enthusiastic advocate of using type-specific serum in treating lobar pneumonia, and his influence was an important factor in switching the routine treat- ment at the Hospital from horse to rabbit antiserum. This change in treatment was very successful and aroused wide interest. A large number of cases were treated with rabbit serum at the Hospital, and Horsfall and his colleagues pub- lished several extensive papers describing the clinical results. The use of this new method caught on generally. Commercial drug houses began producing rabbit antiserum, not only against types I and II, but also against a myriad of the rarer varieties. Horsfall, working with Kenneth Goodner, accompanied this clinical work with a tremendous burst of laboratory activity in which they studied the comparative immunology of horse and rabbit sera in detail. These sera were found to differ from each other in a number of fundamental ways. In the space of a little more than a year, Hors fall and his colleagues published some twenty-three papers on these systems. Thirty or more immuno- logical differences were highlighted, many of which were inter- preted as suggesting distinct therapeutic advantages for the rabbit antibody.

FRANK LAPPIN HORSFALL, JR. 237 Horsfall remained! at the Hospital for three years and during his last year was Chief Resident Physician, a position which greatly increased his clinical responsibilities. Avery at the time was in the midst of his fascinating and fundamental work on the transforming principle. Horsfall was very familiar with all the current details of that work, which had been formalized by Avery into a series of personal lectures known as the Red Seal records. Frank Horsfall frequently sat at Avery's feet adsorbing the gospel, which he later was able to repeat ire minute detail and often did so with great gusto. Yet he never did any research with Avery, much as he admired his whole approach. Their scientific style was entirely different, and Horsfall would have had a most difficult time adjusting to Avery's idiosyncrasies. For Horsfall, the transforming principle must have seemed far away from the world of patients. Although the Rockefeller Hospital was at this time a prime source of candidates for academic positions in medical schools throughout the country, positions within the Hospital itself were at a premium. Nevertheless it became clear within a very short time that Horsfall's future would be in the Rockefeller Institute. It is difficult to assess the reasons for this early popu- larity which lay partly in his ability to see problems clearly, to apply himself to the problem with enormous energy, and then finally to present his results in a way which seemed simultane- ously to be both conservative and expansive, romantic yet con- vincing. Thomas Rivers, who was a very influential person in American medicine at that time, was extremely devoted to Horsfall and played a large part later in promoting him as his own successor at the Rockefeller Institute Hospital. It came as no surprise when in 1937 Horsfall resigned from the Hospital and accepted a staff position with the International Health Division of the Rockefeller Foundation. The change in employer was almost imperceptible. The principal Foundation laboratories were in fact housed at the Rockefeller Institute,

238 BIOGRAPHICAL MEMOIRS and Foundation scientists were treated as part of the family. Horsfall's daily contacts with staff members in the Hospital and the Institute continued as before, including his exceptionally close relationship with Rivers, a friendship which was now further cemented by the transformation of Horsfall into a · . vlro OglSt. The Foundation had made a reputation for itself in virology through its pioneering work on yellow fever, and its leaders were anxious to continue this record of preeminence through an attack on the influenza problem. Horsfall became head of a laboratory section, previously organized by Thomas Francis, Jr., and the time seemed really ripe for developing a prophylactic agent against epidemic influenza. The virus of influenza had been isolated only four years before, and the Foundation offered Horsfall a very large technical staff, abundant laboratory space, generous financial support, and a sizeable professional staff that was equipped by experience to do large-scale fieldwork and to tackle epidemic problems on an international scale. It is somewhat ironic that Horsfall stepped out of the lobar pneumonia scene just as it was undergoing drastic change. The elaborate type-specific serotherapy routines which had been very painstakingly developed in the mid-thirties were briskly and permanently swept away with the advent of chemotherapy and antibiotics. This had little to do with Horsfall's change of employer at this time, but does reflect the sweeping pace of medical advances. During his three years on the pneumonia service, he hacl received excellent training in immunology. Plunging into virology was to be a new experience, and he quickly became a master of the fundamentals. Once again, he threw himself wholeheartedly into a new activity, which was to occupy his attention for several years. Before leaving the Hospital, Horsfall married Norma Cam- pagnari, who worked there as a nurse. It was a most successful marriage. She was a quick, merry, and very lively person and a

FRANK LAPPIN HORSFALL, JR. 239 gracious hostess. Horsfall's domestic life was always important to him, and he devoted much time to it in spite of numerous external demands. They had three children, and he was very much attached to them all. The Foundation provided a proper setting for an individual of Horsfall's brilliant and expansive outlook. In addition to his major projects, he was able to devote much of his time to some very fundamental biological problems, and one of these areas was quantitative biology. He became involved with and obvi- ously enjoyed the design and execution of mechanical projects like a low-temperature storage cabinet or a complicated ventila- tion system for a single room containing a large number of ferrets that had to be individually housed. The latter project was so successful that it enabled him to conduct experiments on the highly contagious distemper virus without danger of spontane- . ~ . Ous cross-~ntect~on. The research was nearly all on influenza virus, and at that time it was necessary to measure virus concentration by intra- nasal inoculation of material into mice. To achieve any reason- able sort of accuracy required the infection of large numbers of animals, followed by individual isolation during the incubation period. Nevertheless, Horsfall did very large, highly quantitative experiments with influenza, in which he attempted to work out the amount of antibody required to neutralize different amounts of virus in the inoculum. This was the beginning of a long and complicated experimental series on neutralization, carried out with great care and repeated many times in the years which followed. The idea of these experiments was to develop some concep- tion of the mechanism of neutralization. He pushed the problem as hard as he could with the techniques at his command, but it was not until many years later that the mystery of neutralization began to unravel, and it was learned that much simpler host systems were essential to understand neutralization mechanisms.

240 BIOGRAPHICAL MEMOIRS Shortly after starting work faith the Foundation, Horsfall took time out for a six-month sabbatical with Arne Tiselius at Uppsala. At that time Tiselius was carrying out his important pioneer work on the electrophoresis of macromolecules. A1- though Horsfall published a couple of papers with Tiselius in the field of physical chemistry, it is clear that he could not use this experience in virology without wandering far afield from his customary goals. The main attraction of the Foundation position was the possibility of studying human influenza infection on a vast scale and attempting prophylaxis against the disease. The Foundation was well equipped for this sort of venture. With its previous experience in yellow fever research, it had developed numerous experienced epidemiologists and other fieldworkers whose value in executing the experiments that were planned in New York would be difficult to exaggerate. In his first years with the Foundation, Horsfall carried out some routine but straightfor- ward investigations of influenza epidemics. This work, in a very new field, carried the mark of competence with it. A ferret colony was an essential resource in carrying out influenza work at that time, and during the course of some early experiments, a spontaneous epidemic of distemper broke out in the Foundation's animal house and nearly all the animals were lost. To prevent a recurrence of this disaster, all new ani- mals were immunized, in most cases using a formalinized spleen from a spontaneously infected animal. Later, some of these im- munized animals were found to have mysteriously acquired high anti-influenza titers. It occurred to Horsfall at once that dis- temper virus infection might have some sort of cooperative effect in inducing high-level and persistent antibody responses to influenza virus. It was a fascinating idea, and a "complex" vaccine containing both influenza and distemper virus was quickly developed for use in human beings. The Foundation provided large-scale pro-

FRANK LAPPIN HORSFALL, JR. 241 auction facilities for the new product, which was made by growing both viruses in chick embryos and then freeze-drying a formalinized extract. With the threat of a widespread epidemic (1940-1941), there was no time to do a lot of testing on prepara- tions before they could be used in human experiments. There were some feverishly performed experiments in laboratory ani- mals and man, but they were not completed in time to modify the large-scale experiments which were being contemplated in the field. Large amounts of vaccine were prepared and shipped to Great Britain, which was at war, just in case the epidemic became intolerable. The British examined the preparations in great detail, but did not utilize an opportunity to try them. In the United States, however, Horsfall conducted a large-scale demonstration, vaccinating, under well-controlled circum- stances, volunteers in a large number of state prisons up and down the Eastern Seaboard. The experiment was carried out in magnificent style. E. R. Rickard, who was Horsfall's chief field marshal, was a master at this type of human experiment. Not only was the distribution of inoculations carefully controlled, but a great deal of data was obtained on individuals through attempts at virus isolation and by determining pre- and post-infection antibody titers. For- tunately, the inoculations were completed a relatively short time before the onset of the epidemic, and the use of a large number of population groups proved valuable in the final anal- ysis of the results. In spite of the excellence of organization and the occurrence of a large-scale epidemic in the wake of vaccination, the results were very disappointing. Although antibody rises had been in- duced in many vaccine recipients, the rise in titer was small and evanescent, and the reduction in case rate was in most institu- tions negligible or at best marginal. Only in a couple of places was there as much as a 50 percent drop in incidence following

242 BI OGRAPHICAL MEM OIRS vaccination, ant! it turned out that in these places the batch of vaccine used had had the highest virus titer before formalini- zation. When all the laboratory tests on the complex vaccine were finally in, the results explained in some degree the disappointing field tests. In general the virus content of the vaccine was low, and the initially promising effect of distemper virus in boosting antigenicity could never be reproduced. It is again rather ironic that, just as these results were being recorded, new methods of obtaining high virus titers, as well as high virus purity, were being developed. It wasn't until several years later that vaccines made with these improved reagents were tested and gave the first bona fide protection against influenza in the field. Even years later the secret of obtaining substantial and prolonged effects against epidemic influenza is still a formidable problem, and the earliest experiences with the "complex" vaccine were by no means unique. Just as the episode of the vaccine trial was coming to a close, Horsfall was called back to the Rockefeller Institute Hospital, where he received a lifetime appointment as a full member. Essentially he took over Rivers' Department of Virology, but he peopled it with entirely new personnel, and in his new pro- gram he once again confined his attention to respiratory disease. Rivers, who was now Director of the Rockefeller Institute Hospital, played a very important role in shaping developments within that organization. The return of Horsfall, with the pos- sibility that he might become the Hospital's next Director, brought Rivers' planning to a climax. By now the United States had entered the war, and Rivers organized a naval unit at the Hospital, most of which later went to Guam under his command. The remainder of this unit stayed on at Rockefeller Institute with Horsfall as the commanding officer, and as a group they worked on respiratory diseases, espe- cially those that they felt might have a virus etiology such as

FRAN K LAPPIN HORSFALL, JR. 243 atypical pneumonia. This naval unit continued right on into the post-war period with little change in its structure, problems, or personnel. Thus in 1941 Horsfall began the main period in his scientific life, which was to last about twenty years, and during which he had magnificent resources, was able to devote his full time to science, and was free to determine his own course of action. In the latter part of this period, his duties would become more and more administrative, culminating finally in his move to Sloan- Kettering. In 1941, however, the Rockefeller Institute provided a most salubrious climate for research. The place was populated by a scientific elite, mainly oriented toward biology and com- pletely involved in research activity in a life which was unen- cumbered by teaching or institutional politics, as might be the . . . case in a university. Horsfall had a widely recognized and wel~justified reputa- tion for fostering research activities in his department in such a way that the individual investigators enjoyed both great freedom and superb stimulation. By now Horsfall hac! received a thorough, although informal, education in the immunology, bacteriology, and virology of the day; and characteristically, as in the past, he continued to work in areas which were closely relevant to infections in man. Hospital beds were available, and the group took on as its main project the search for the etiology of a recently developed entity called atypical pneumonia. In the previous few years this affliction had replaced lobar pneumonia as the principal acute respiratory disease of man. In this new situation Horsfall again threw all of his energy into the attack, and a multipronged effort was mounted. A puta- tive agent was isolated in mice by serial passage of human lung material. An agent was isolated in the mongoose from a similar source. Still other investigations involved the use of cotton rats. A gram-positive bacillus was isolated from human cases of atypical pneumonia, and the relationship of this organism to

244 BIOGRAPHICAL MEMOIRS the disease was thoroughly explored. This led to the discovery of some rather nonspecific serological responses in the patients suffering from pneumonia. Some of the work suggested a rela- tionship of PVM (pneumonia virus of mice) to the human cli- sease. The volume and detail of their explorations were quite impressive, but none of these efforts led to any firm conclusions at the time regarding the etiology of atypical pneumonia. The search for an agent by Horsfall's group and others turned out to be far ahead of its time, and it was not until the mycoplasmas were delineated as a separate microbial group that investigators were able to determine the causative organism of this kind of pneumonia. In retrospect it was then shown that some of the earlier "virus isolates" (e.g., Eaton's lung passages from cotton rats) did in fact contain what we know now is the agent. It is pertinent at this point to reemphasize the fact that Horsfall's training in basic disciplines was informal and that he approached his main problems, like atypical pneumonia, as a physician. This absence of formal scientific training was also true of the majority of students who came to work with Horsfall, many of whom settled into prominent academic clinical posi- tions after leaving Rockefeller. This approach to viruses pri- marily as agents of disease was quite typical of the virology of the time, and as a result of this approach, the sum of the work done (on say atypical pneumonia) lacked the cohesion that came later, after the discipline had developed a more impressive in- ternal structure. The biological revolution which was to gain momentum in the sixties completely changed the face of virol- ogy, which in the forties and fifties was dominated by clinical viewpoints and hence was somewhat amorphous. During this period at Rockefeller, Horsfall's attention was not confined to the problem of atypical pneumonia. Some years before, while working on influenza with Richard Hahn, he was making some mouse-to-mouse passages of human lung material, and he isolated an agent which he called PVM. This virus was

FRANK LAPPIN HORSFALL, 245 normally latent in mouse colonies, but with passage its virulence could be enhanced so that it would cause pulmonary consolida- tion with a moderate mortality. This agent was to receive inten- sive study from time to time, in part because of its pneumotrop- ism and also because it was thought to be related to the causative agent of some human pneumonias. The disease which it caused in mice was throughly studied in every aspect, including at- tempts at treatment and prophylaxis. In the early stages of this work, it was fount! that the virus agglutinated red cells, and in addition it was shown that some substance in lung extracts also adsorbed to the virus. One of the most striking findings, however, was the discovery that certain high-molecular-weight carbohydrates hac! a distinct therapeutic effect on the pneumonia which the virus induces] in mice. This unexpected finding came about when Horsfall, working with M. McCarty, was looking at the effects of the streptococcus MG (isolated from cases of atypical pneumonia) on PVM infection in mice. They found that a capsular polysaccharicle from this bacil- lus had a profound therapeutic effect on the course of PVM infection in mice. The material was effective even after the disease had become well established and the intact macromole- cule was necessary for therapeutic activity. Later on Horsfall and H. S. Ginsburg found that a similar polysaccharide from Friedlander's bacillus, group B. had an even greater therapeutic effect, and it also worked very well on mumps virus infection, in which the growth of virus was markedly suppressed. All of the foregoing experiments were carried out on infec- tions in complex organisms such as the developing embryo or the adolescent mouse. There never has been an adequate expla- nation of the curative mechanism at work, and the experiments have not been repeated with simpler host cell systems which became available later. Igor Tamm and Horsfall initiated a further series of chemotherapeutic experiments with the benzi- midazoles and their derivatives on influenza virus infection, and thereafter the series was carried on by Tamm and others.

246 BIOGRAPHICAL MEMOIRS During this period Horsfall never forgot his early interest in influenza, and periodically he returned to influenza problems. It was a difficult virus to manage, but it had attractions which were then unknown for other agents; and Horsfall, always in- terested in quantitative biology, continued to study the relation- ship between hemagglutination inhibitors and virus-neutralizing antibodies. He was especially interested in the problem of an- tigenic strain differences between various influenza A isolates and did some very interesting work with I. Archetti showing that the antigenic profile of a number of influenza stocks could be quickly and permanently altered by in ovo passage in the pres- ence of appropriate antibody. This type of experiment furnished the basic information through which the changes found in in- fluenza virus from epidemic to epidemic could be explained, and this information is very fundamental to modern concepts of how the virus operates in nature. Horsfall's interest extended briefly to other viruses from time to time, and his papers include reports on Coxsackie viruses, herpes simplex, mumps, and others. With some of these agents he was exploring the possibility of chemotherapeutic effects. He was also interested in the phenomenon of interfer- ence, in the effects of hormones (such as cortisone), and in metabolic inhibitors like fluoroacetate, which led eventually to the work with benzimidazoles. Perhaps the most notable thing about this period of Horsfall's life was the long series of collaborators who worked with him in the New York laboratory, many of whom subse- quently went out into key positions in the medical-academic world. The list includes such individuals as Lewis Thomas, Edward Curnen, Harry Ginsberg, D. A. J. Tyrrell, M. R. Hille- man, E. D. Kilbourne, Igor Tamm, F. M. Davenport, G. S. Mirick, and Maclyn McCarty. It would be impossible to find a more outstanding group of microbiologists who were connected with any other single laboratory. Because of the way in which Horsfall operated, these individuals often contributed as much

FRANK LAPPIN HORSFALL, JR. 247 as they received, and each one in his way left his mark on the group. It was part of Horsfall's genius that he could at the same time exert a strong influence over the events occurring in his laboratory and also allow great freedom of expression. In 1953 Herbert Gasser retired as Director of the Rocke- feller Institute, and the accession of Detlev Bronk to this post foreshadowed great changes for the organization and all who were connected with it. Within a couple of years, Bronk con- verted the Institute into a University of Science, took in stu- dents, enlarged the faculty, added to the physical plant, and severely shook up its reserved character. During this period of rapid change, Bronk was preoccupied with plans for expansion, and in addition he played a very active role as President of the National Academy of Sciences. As Vice-President and Physician-in-Chief to the Hospital, Horsfall was now second in command. He assumed the respon- sibility for many of the day-to-day tasks in running such an institution, and during this period he was especially appreciated by the older members from Institute days and often devoted a great deal of time and attention to their special problems. He became further and further separated from the laboratory, where, fortunately, Igor Tamm was present to assist in carrying on the old tradition. Prior to this time almost all of Horsfall's papers were published uncler joint authorship, but thereafter he published alone, mainly reviews on such topics as chemotherapy of virus infections and others with which he was familiar. He never gave anyone the impression that he was unhappy with this change, as he slid almost imperceptibly into a totally different kind of existence. Being second in command and defender of the olc! tradition under Bronk was not entirely easy, and when in 1959 the direc- torship of the Sloan-Kettering Institute became available, the trustees (including a Rockefeller brother as chairman) offered the post to Horsfall, who accepted and made the move just across York Avenue.

248 BIOGRAPHICAL MEMOIRS Replacing Cornelius Rhoades was difficult, for SIoan-Ketter- ing at the time was virtually the single-handed creation of Rhoades, who had built it up in the course of some twenty years. He made many of the staff appointments ant! followed many individual research programs in a very personal way. Horsfall's style was entirely different. He made few immediate changes, but in time he developed his own very loyal staff. Previously the emphasis at Sloan-Kettering was on studies of the chemical car- cinogens and on cancer chemotherapy. This slant was not changed at once, and much of this kind of activity was preserved. Naturally the new emphasis was on the viral etiology of cancer and on molecular biology, both of which were just coming into prominence elsewhere. Horsfall was a staunch advocate of basic research in biology, and he was eclectic in his approach toward the tumor problem. He was conservative in his estimates of future progress in the cancer field and was unwilling to make superficial and encouraging predictions. This attitude was re- peatedly expressed in the numerous reviews on the cancer prob- lem which he began writing at this time. When Horsfall came to Sloan-Kettering there was already a large building program under way, which he saw to completion. He also played the most important role in added staffing. In regard to the latter, he was also very reserved and relied heavily on a board of scientific consultants, with whom he met several times a year ant! went over many of the details of ongoing scien- tific programs. In the ensuing discussions of scientific merit, he was forthright and outspoken and used the highest standards of judgment, but he also listened intently to advice that was given. Because of his conservative attitude, things changed slowly, and his effect on the institution became evident only in his latest years. Outside of the institutions in which he worked, Horsfall's life was a continuous flurry of activity. He was especially well known for his leading role on various boards of both local and national character. On the federal level he was at various times

FRANK LAPPIN HORSFALL, JR. 249 a member of the President's Commission on Heart Disease, Cancer, and Stroke and of the Defense Science Board of the Department of Defense. In the years immediately after the war, he served as consultant to the Surgeon General of the U.S. Army and was on the Commission on Immunization of the Army Epidemiological Board. Outside of the government he was active in the National Foundation for Infantile Paralysis for many years, both before the vaccination campaign for polio- myelitis and after the focus of attention was switched to con- genital diseases. He was a member of many scientific advisory bodies for such organizations as the Institute of Microbiology at Rutgers, the Oklahoma Research Foundation, and the Roscoe B. Jackson Memorial Laboratory at Bar Harbor, Maine. Even more impressive was his devotion to the affairs of New York City, where he was a member of the Board of Directors of the Public Health Research Institute from 1955 on and was chairman of its Research Council for a large part of that time. In addition he was a very important influence in the organiza- tion and development of the Health Research Council of New York City, which for many years played a very important role in public health research. To this sort of managerial responsibility Horsfall brought a very special talent. He was always completely familiar with the underlying structure in any organization that he served, and he always came to meetings fully briefed and with all of his home- work well in hand. In the meetings themselves he played an especially important role in presenting and analyzing difficult problems, a role which he performed with such remarkable clarity that the problems would be understood by all, including the lay people who were present. Both in official and in private discussions, he made frequent use of hyperbole to drive home his point. His exaggerations were sometimes outrageous and were frequently coupled with a puckish manner. Even with long experience it was difficult to tell if he was serious. Mention was made earlier of his overriding interest in

250 BIOGRAPHICAL MEMOIRS clinical medicine, an interest which became obvious in a number of ways. In addition to devoting a large portion of his scientific time to problems which had clinical application, he also devoted a great deal of time and effort to writing and speaking, very often on clinical topics. He contributed a great many articles to some of the best-known medical textbooks, and these dealt generally but not exclusively with virus diseases and their treatment. He edited (with Igor Tamm) and wrote extensively for the third edition of the widely used textbook, Virus and Rickettsiat Diseases of Man. He also wrote a large number of reviews on chemotherapy in which the emphasis was frequently on agents of potential use in man. During his lifetime he received many honors, dating from the time of his graduation from Medical School. He was given the Eli Lilly Award in Bacteriology and Immunology in 1937, the Casgrain and Charbonneau Award in Medicine from McGill in 1942, the John Lewis Prize from the American Philosophical Society in 1959, and the 50th Anniversary Gold Medal Award of Peter Bent Brigham Hospital in 1963. Horsfall was elected to the Academy in 1948 and served on its Committee of Science and Public Policy (cosPuP) from 1963 to 1966. He became a member of the American Philosophical Society in 1956 and of the American Academy of Arts and Sciences in 1967. He had memberships in many professional societies, including the American Society for Clinical Investi- gation and the Association of American Physicians, to which he was elected in 1937 and 1942, respectively. He was a member of the Harvey Society and served as its President in 1956, and he was a lifelong member of the American Association of Immunol- ogists and its President in 1967. A long list of other societies includes the Royal College of Physicians and Surgeons of Canada and the Royal Society of Medicine of Great Britain. He received honorary degrees from the University of Alberta, McGill Uni- versity, and Uppsala University.

FRANK LAPPIN HORSFALL, JR. 251 Horsfall served on the editorial boards of a number of pro- fessional journals, including the Journal of Experimental Medi- cine, the American Journal of Public Health, Virology, Excerpta Med ica, and the Journal of Immunology. During his years at Sloan-Kettering, Horsfall lived on the top floor of the Hospital-Institute complex, but since he found life in city apartments to be unbearably stifling, he also main- tained a home in upper Westchester County, New York, where he frequently spent long weekends. It was here that he enjoyed the pleasures of working with his hands. He was quite skillful as a carpenter and this and cultivation of the soil gave him relief from the strenuous tensions of administrative duties. It was here that he enjoyed the intimacy of family life. He is survived by his wife, Norma, who resides in Silver Spring, Maryland; a son Frank L. Horsfall III, a microbiologist and director of research in an organization concerned with environmental science; and two daughters Susan Shahmanesh who lives in Brooklyn, New York, and Mary Sullivan who lives in Leesburg, Virginia. There are three grandchildren. During the fall of 1970 Horsfall felt himself beginning to fail. He had decided to retire just before it was discovered that he had cancer, of which he died on February 19, 1971. His death left a void which was widely felt, not only among his colleagues and staff, but also in the entire scientific community. IT IS A PLEASURE to acknowledge the considerable assistance of Mrs. Norma Horsfall and also of Marilyn Moor of the Memorial Sloan- Kettering Cancer Center in furnishing important information and a bibliography. I am also indebted to several previous biographers, especially an extended account by Colin McLeod, published in the Yearbook of the American Philosophical Society (1971, pp. 127-32~. Informal short biographies by Igor Tamm, Alexander Beam, and Chester Southam were also available. I am indebted to the University of Washington Alumni Bulletin for information collected at the time Dr. Horsfall received recognition as a distinguished alumnus.

252 BIOGRAPHICAL MEM OIRS BIBLIOGRAPHY 1930 With T. Beattie. An anomalous facial muscle. l. Anat., 65: 145~8. 1932 With C. N. H. Long. The recovery process after exercise in the mammal. II. Conversion of infused d-lactic acid into muscle. I. Biol. Chem., 95:715-33. 1934 Formaldehyde hypersensitiveness. An experimental study. J. Im- munol., 27:569-81. Formaldehyde and serum proteins. Their immunological charac- teristics. l. Immunol., 27: 553-68. 1935 With W. R. Smith. Schuller-Christian syndrome. Lipoid granu- lomatosis with defects in the bones, exophthalmos and diabetes insipidus. Quart. l. Med., n.s. 4: 37-51. With K. Goodner. Relation of the phospholipins to the reactivity of antipneumococcus sera. Proc. Soc. Exp. Biol. Med., 32:1329- 30. With K. Goodner. The protective action of type I antipneumococcus serum in mice. I. The quantitative aspects of the mouse protec- tion test. l. Exp. Med., 62:359-74. With K. Goodner. Lipids and immunological reactions. I. The rela- tion of phospholipins to the type-specific reactions of antipneu- mococcus horse and rabbit sera. l. Exp. Med., 62:485-503. 1936 - With K. Goodner. Lipids and immunological reactions. II. Further experiments on the relation of lipids to the type-specific reactions of antipneumococcus horse and rabbit sera. l. Immunol., 31:135- 40. With K. Goodner. Lipids and immunological reactions. III. Lipid content of specific precipitates from type I antipneumococcus sera. J. Exp. Med., 64:583-99. With K. Goodner. Lipids and immunological reactions. IV. Lipid

FRAN K LAPPIN HORSFALL, JR. 253 patterns of specific precipitates from type I antipneumococcus sera. J. Exp. Med., 64:855-63. With K. Goodner. The protective action of type I antipneumo- coccus serum in mice. IV. The prozone. J. Exp. Med., 64:369-75. With K. Goodner. The protective action of type I antipneumo- coccus serum in mice. V. The effect of added lipids on the protective mechanism. J. Exp. Med., 64:377-83. Congenital family clubbing. Can. Med. Assoc. I., 34: 145~9. With T. J. Abernethy and C. M. MacLeod. Pneumothorax therapy in lobar pneumonia. Bulletin of the Johns Hopkins Hospital, 58:35-62. With K. Goodner and J. H. Bauer. Ultrafiltration of type I anti- pneumococcal sera. Proc. Soc. Exp. Biol. Med., 34:617-19. With K. Goodner. The complement fixation reaction with pneu- mococcus capsular polysaccharide. J. Exp. Med., 64:201-16. With K. Goodner and C. M. MacLeod. Type specific antipneu- mococcus rabbit serum. Science, 84:579-81. 1937 With K. Goodner, C. M. MacLeod, and A. H. Harris II. Anti- pneumococcus rabbit serum as a therapeutic agent in lobar pneumonia. I. Am. Med. Assoc., 108: 1483-90. With K. Goodner. Passive anaphylactic sensitivity to pneumococcus capsular polysaccharide. l. Immunol., 33:259-63. With K. Goodner. The purpuric reaction produced in animals by derivatives of the pneumococcus. Proc. Soc. Exp. Biol. Med., 37: 178-80. The control of lobar pneumonia. Can. Pub. Health l., 28:476-84. With K. Goodner. Properties of the type specific proteins of anti- pneumococcus sera. I. The mouse protective value of type I sera with respect to the precipitin content. l. Exp. Med., 66:413-24. With K. Goodner. Properties of the type-specific proteins of anti- pneumococcus sera. II. Immunological fractionation of type I antipneumococcus horse and rabbit sera. l. Exp. Med., 66:425- 35. With K. Goodner. Properties of the type-specific proteins of anti- pneumococcus sera. III. Immunochemical fractionation of type I antipneumococcus horse and rabbit sera. J. Exp. Med., 66:437- 48.

254 BIOGRAPHICAL MEMOIRS With K. Goodner and R. J. Dubos. Type specific antipneumococcus rabbit serum for therapeutic purposes. J. Immunol., 33:279-95. 1938 With K. Goodner and C. M. MacLeod. Antipneumococcic rabbit serum as a therapeutic agent in lobar pneumonia. II. Additional observations in pneumococcus pneumonias of nine different types. N.Y. State l. Med., 38:245-55. The characteristics of antipneumococcus sera produced by various animal species. l. Bacterial. 35:207-12. With T. P. Hughes and E. G. Pickels. A method for determining the differential sedimentation of proteins in the high speed concentration centrifuge. l. Exp. Med., 67:941-52. With K. Goodner and l. H. Bauer. The neutralization of pneumo- coccal capsular polysaccharide by the antibodies of type specific antisera. l. Immunol., 35:451-63. With K. Goodner and l. H. Bauer. Some factors which affect the ultrafiltration of antipneumococcal sera. J. Immunol., 35:439-49. 1939 With A. Tiselius. Mixed molecules of hemocyanins from two dif- ferent species. l. Exp. Med., 69:83-101. With R. G. Hahn. A pneumonia virus of Swiss mice. Proc. Soc. Exp. Biol. Med., 40:684-86. Neutralization of epidemic influenza virus. The linear relationship between the quantity of serum and the quantity of virus neu- tralized. l. Exp. Med., 70:209-22. With A. Tiselius. Electrophoretic technique. I. Electrophoresis of hemocyanins. Arkiv foer Kemi Mineral. Geol., 13A (18) . 20 pp. Characteristics of protein boundaries as shown by scale method electrophoretic diagrams. Ann. N.Y. Acad. Sci., 39:203-7. 1940 With R. G. Hahn. A latent virus in normal mice capable of pro- ducing pneumonia in its natural host. J. Exp. Med., 71:391-408. With R. G. Hahn and E. R. Rickard. Four recent influenza epi- demics: An experimental study. T. Clin. Invest., 19:379-92. With E. H. Lennette. A complex vaccine effective against different strains of influenza virus. Science, 91 :492-94.

FRANK LAPPIN HORSFALL, JR. 255 With E. H. Lennette. Studies on epidemic influenza virus. The nature and properties of the complement-fixing antigen. J. Exp. Med., 72:233~5. With E. H. Lennette. The synergism of human influenza and canine distemper viruses in ferrets. I. Exp. Med., 72:247-59. With i. H. Bauer. Individual isolation of infected animals in a single room. l. Bacteriol., 40: 569-80. With l. M. Weir. The recovery from patients with acute pneumo- nitis of a virus causing pneumonia in the mongoose. I. Exp. Med., 72:595-610. A low temperature storage cabinet for preservation of viruses. I. Bacteriol., 40:559-68. With E. H. Lennette, E. R. Rickard, C. H. Andrewes, W. Smith, and C. H. Stuart-Harris. The nomenclature of influenza. Lancet, 2:413-14. With E. R. Rickard and E. H. Lennette. A comprehensive study of influenza in a rural community. Public Stealth Rep., 55:2146-67. Present status of knowledge concerning influenza. Am. l. Public Health, 30:1302-10. 1941 With E. H. Lennette. Neutralization of influenza A virus by human serum. l. Exp. Med., 73:327-33. With E. H. Lennette and E. R. Rickard. A complex vaccine against influenza A virus. l. Exp. Med., 73:335-55. With E. H. Lennette. Studies on influenza virus. The complement fixing antigen of influenza A and swine influenza viruses. l. Exp. Med., 73:581-99. With E. H. Lennette, E. R. Rickard, and G. K. Hirst. The diverse etiology of epidemic influenza. Public Health Rep., 56:1777-88. With E. R. Rickard and G. K. Hirst. The correlation between neu- tralizing antibodies in serum against influenza viruses and sus- ceptibility to influenza in man. Public Health Rep., 56:1819-34. With E. H. Lennette, E. R. Rickard, and G. K. Hirst. Studies on the efficacy of a complex vaccine against influenza A. Public Health Rep., 56:1863-75. With E. R. Rickard. Neutralizing antibodies in human serum after influenza A. The lack of strain specificity in the immunological response. I. Exp. Med., 74:433-39.

256 BIOGRAPHICAL MEMOIRS Influenza. Ann. Intern. Med., 15:811-16. With E. R. Rickard. The relationship between neutralizing anti- bodies against influenza A virus in the sera of mothers and infants. l. Immunol., 42:267-72. Recent studies in influenza. Am. l. Public Health, 31: 1275-80. 1942 With G. K. Hirst, E. R. Rickard, and L. Whitman. J. Exp. Med., 75:495-511. The present status of the influenza problem. l. Am. Med. Assoc., 120:284-87. 1943 Human influenza. In: Virus Diseases, the 1942 Messenger Lectures, pp. 113-43. Ithaca, N.Y.: Cornell Univ. Press. With L. Thomas, E. C. Curnen, G. S. Mirick, and l. E. Ziegler. Complement fixation with different antigens in primary atypical pneumonia. Proc. Sac. Exp. Biol. Med., 52: 121-25. With E. C. Curnen, G. S. Mirick, L. Thomas, and l. E. Ziegler. A virus recovered from patients with primary atypical pneu- monia. Science, 97:289-91. With L. Thomas, G. S. Mirick, E. C. Curnen, and I. E. Ziegler, Jr. Serological reactions with an indifferent streptococcus in pri- mary atypical pneumonia. Science, 98:566-68. 1944 With T. E. Ziegler, Jr. Interference between the influenza viruses. I. The effect of active virus upon the multiplication of influenza viruses in the chick embryo. J. Exp. Med., 79:361-77. With J. E. Ziegler, fir., and G. I. Lavin. Interference between the influenza viruses. II. The effect of virus rendered non-infective by ultraviolet radiation upon the multiplication of influenza viruses in the chick embryo. J. Exp. Med., 79:379-99. With G. S. Mirick, L. Thomas, and E. C. Curnen. Studies on a non- hemolytic streptococcus isolated from the respiratory tract of human beings. I. Biological characteristics of streptococcus MG. I. Exp. Med., 80:391-406. II. Immunological characteristics of streptococcus MG. j. Exp. Med. 80:407-30. III. Immunological relationship of streptococcus MG to Streptococcus salivarius Type I. T. Exp. Med., 80:431-40.

FRAN K LAPPIN HORSFALL, JR. 1945 ~7 With E. C. Curnen, G. S. Mirick, l. E. Ziegler, Jr., and L. Thomas. Studies on primary atypical pneumonia. I. Clinical features and results of laboratory investigations. i. Clin. Invest., 24:209-26. With L. Thomas, G. S. Mirick, E. C. Curnen, and l. E. Ziegler, Jr. Studies on primary atypical pneumonia. II. Observations con- cerning the relationship of a non-hemolytic streptococcus to tl~e disease. l. Clin. Invest., 24:227~0. 1946 With E. C. Curnen. Studies of pneumonia virus of mice. I. The precision of measurements in vivo of the virus and antibodies against it. i. Exp. Med., 83:25~. With E. C. Curnen. Studies of pneumonia virus of mice. II. Im- munoIogical evidence of latent infection with the virus in numerous mammalian species. I. Exp. Med., 83:43-64. With E. C. Curnen. Studies of pneumonia virus of mice. III. Hemagglutination by the virus: The occurrence of combination between the virus and a tissue substance. .T- Exp. Med., 83: 105-32. Primary Atypical Pneumonia. N.Y. State l. Med., 46: 1810-14. 1947 With E. C. Curnen and E. G. Pickels. Centrifugation studies on pneumonia virus of mice (PVM). ]. Exp. Med., 85:23-38. With E. C. Curnen. Properties of pneumonia virus of mice (PVM) in relation to its state. l. Exp. Med., 85:39-53. With J. E. Ziegler, fir., E. C. Curnen and G. S. Mirick. Diagnosis of acute respiratory infections. Am. l. Med. Sci., 213:268-81. With M. McCarty. The modifying effects of certain substances of bacterial origin on the course of infection with pneumonia virus of mice (PVM). J. Exp. Med., 85:623~6. Primary atypical pneumonia. Ann. Intern. Med., 27:275-81. Virus och virussjukdomar has manniskan. Nord. Med., 34:1333~1. Latenta virus och deras relation till infektioner. Nord. Med., 35: 1611-18. Hemagglutination och forekomsten av bundet virus. Nord. Med., 35: 1739-46. With M. Volkert, C. Pierce, and R. J. Dubos. The enhancing effect

258 BIOGRAPHICAL MEMOIRS of concurrent infection with pneumotropic viruses on pulmonary tuberculosis in mice. l. Exp. Med., 86:203-13. With M. Volkert. The effect of sulfhydryl groups on pneumonia virus of mice (PVM). J. Exp. Med., 86:383-91. \Vith M. Volkert. Studies on a lung tissue component which com- bines with pneumonia virus of mice (PVM). if. Exp. Med., 86: 393-407. With H. S. Ginsberg and W. G. Goebel. Inhibition of mumps virus multiplication by a polysaccharide. Proc. Soc. Exp. Biol. Med., 66:99-100. With M. McCarty. The antagonistic effect of certain substances of bacterial origin on the course of infection with pneumonia virus of mice (PVM). Trans. Assoc. Am. Physicians, 60:18-21. 1948 With H. S. Ginsberg and W. G. Goebel. The inhibitory effect of polysaccharide on mumps virus multiplication. l. Exp. Med., 87:385-410. With H. S. Ginsberg and W. G. Goebel. The effect of polysaccha- rides on the reaction between erythrocytes and viruses, with particular reference to mumps virus. l. Exp. Med., 87:411-24. Primary atypical pneumonia and influenza~iagnosis, prevention, treatment. Bull. N.Y. Acad. Med., 24:431-46. With S. E. Bjorkman. The production of persistent alteration in influenza virus by lanthanum or ultraviolet irradiation. l. Exp. Med., 88 :445-61. With P. H. Hardy, fir. Reactions between influenza virus and a component of allantoic fluid. J. Exp. Med., 88:463-83. With F. M. Davenport. Assocative reactions of pneumonia virus of mice (PVM) and influenza viruses: The effects of pH and electro- lytes upon virus host-cell combinations. l. Exp. Med., 88:621~4. 1949 With H. S. Ginsberg. Concurrent infection with influenza virus and mumps virus or pneumonia virus of mice (PVM) as bearing on the inhibition of virus multiplication by bacterial polysaccha- rides. J. Exp. Med., 89:37-52. With O. Lahelle. Multiplication of influenza virus in dead chick embryos. Proc. Soc. Exp. Biol. Med., 70:547-51.

FRAN K LAPPIN HORSFALL, JR. 259 With H. S. Ginsberg. Chemotherapy of viral infections. In: Evalua- tion of Chemotherapeutic Agents, pp. 170-80. N.Y.: Columbia Univ. Press. Prospects for the control of viral diseases by chemical agents. Can. Med. Assoc. I., 60:439~7. With P. K. Olitsky, l. Casals, D. L. Walker, and H. S. Ginsberg. Preservation of viruses in a mechanical refrigerator at —24°. J. Lab. Clin. Med., 34:1023-26. With E. D. Kilbourne. A chemical method for the detection of virus infection of the chick embryo. Proc. Soc. Exp. Biol. Med., 71: 708-13. With O. Lahelle. Hemagglutination with the GDVIII strain of mouse encephalomyelitis virus. Proc. Soc. Exp. Biol. Med., 71: 713-18. With H. S. Ginsberg. A resistant variant of mumps virus. Multi- plication of the variant in the presence of inhibitory quantities of Friedlander bacillus polysaccharide. I. Exp. Med., 90:393~07. With H. S. Ginsberg. A labile component of normal serum which combines with various viruses. Neutralization of infectivity and inhibition of hemagglutination by the component. l. Exp. Med., 90:475-95. 1950 With F. M. Davenport. Further studies on the associative reactions of pneumonia virus of mice (PVM) and influenza viruses. Com^ bination with various animal tissues and absorbents. J. Exp. Med., 91:53-64. With D. L. Walker. Lack of identity in neutralizing and hemag- glutination-inhibiting antibodies against influenza viruses. J. Exp. Med., 91:65-86. Advances in the diagnosis of virus infections. Bull. N.Y. Acad. Med., 26:3-19. With I. Tamm. Characterization and separation of an inhibitor of viral hema~lutination present in urine. Proc. Soc. Exo. Biol. Med., 74:108-14. .~, . Chemotherapy in viral infections. (The Musser Lecture) Am. l. Med. Sci., 220:91-102. Approaches to the control of viral diseases. Bact. Rev., 14:219-24. With I. Archetti. Persistent antigenic variation of influenza A

260 BIOGRAPHICAL MEMOIRS viruses after incomplete neutralization in eve with heterologous immune serum. J. Exp. Med., 92:441-62. With I. Tamm and E. D. Kilbourne. Comparison of influenza B strains from the 1950 epidemic with strains from earlier epi- demics. Proc. Soc. Exp. Biol. Med., 75:89-92. With H. S. Ginsberg. The implications of chemical interruption of viral multiplication. Trans. Assoc. Am. Physicians, 63:118-21. 1951 With H. S. Ginsberg. The dependence of the pathological lesion upon the multiplication of pneumonia virus of mice (PVM). Kinetic relation between the degree of viral multiplication and the extent of pneumonia. it- Exp. Med., 93:139-50. With H. S. Ginsberg. Characteristics of the multiplication cycle of pneumonia virus of mice (PVM). ]. Exp. Med., 93:151-60. With H. S. Ginsberg. Therapy of infection with pneumonia virus of mice (PVM). Effect of a polysaccharide on the multiplication cycles of the virus and on the course of the viral pneumonia. J. Exp. Med., 93: 161-71. Studies on non-hemolytic streptococci isolated from the respiratory tract of man. The antigenic basis for type specific reactions with Streptococcus salivarius and non-levan-forming streptococci. J. Exp. Med., 93:229-45. With E. D. Kilbourne. Increased virus in eggs injected with corti- sone. Proc. Soc. Exp. Biol. Med., 76:116-18. With H. S. Ginsberg. An improved CO2 cabinet for low temperature storage of infectious agents with gaseous CO2 excluded from the specimen compartment. J. Bacterial., 61:443-51. With E. D. Kilbourne. Lethal infection with Coxsackie virus of adult mice given cortisone. Proc. Soc. Exp. Biol. Med., 77:135-38. With E. D. Kilbourne. Primary herpes simplex virus infection of the adult: With a note on the relation of herpes simplex virus to recurrent aphthous stomatitis. Arch. Int. Med., 88:495-502. With E. D. Kilbourne. Studies of herpes simplex virus in newborn mice. l. Immunol., 67:321-29. With H. S. Ginsberg. Interference between mumps virus and pneu- monia virus of mice (PVM). Fate of mumps virus in the mouse lung. J. Immunol., 67:369-77.

FRANK LAPPIN HORSFALL, JR. 261 With E. D. Kilbourne. Mouse-egg neutralization. Neutralization in the mouse of influenza viruses not adapted to the mouse. J. Immunol., 67:43 1-36. With E. D. Kilbourne and H. C. Anderson. Concurrent infection with influenza A and B viruses in a single epidemic of influenza. I. Immunol., 67:547-58. 1952 With I. Tamm. A mucoprotein derived from human urine which reacts with influenza, mumps and New Castle disease viruses. J. Exp. Med., 95:71-97. With G. E. Perlman and I. Tamm. An electrophoretic examination of a urinary mucoprotein which reacts with various viruses. I. Exp. Med., 95:99-104. With H. S. Ginsberg. Quantitative aspects of the multiplication of influenza A viruses in the mouse lung. Relation between the degree of viral multiplication and the extent of pneumonia. l. Exp. Med., 95: 135-45. Factors concerned with viral proliferation in vivo. Ann. N.Y. Acad. Sci., 54:926-35. With I. Tamm and K. Folkers. Inhibition of influenza virus multi- plication by 2,5-dimethlbenzimidazole. Yale l. Biol. Med., 24: 559-67. With M. R. Hilleman. Comparison of the antigenic patterns of influenza A virus strains determined by in ovo neutralization and hemagglutination inhibition. J. Immunol., 69: 343-56. With D. A. J. Tyrrell. A procedure which eliminates nonspecific inhibitor from human serum but does not affect specific anti- bodies against influenza viruses. I. Immunol., 69:563-74. With I. Tamm. Variation demonstrable by methods other than serological. Bull. N.Y. Acad. Med., 28:765-68. With I. Tamm and H. S. Ginsberg. Antigenic similarity between the first and later egg passage strains of freshly recovered in- fluenza A viruses. Proc. Soc. Exp. Biol. Med., 81:94-98. With W. i. Mogabgab. Effect of sodium monofluoroacetate on the multiplication of influenza viruses, mumps virus and pneumonia virus of mice (PVM). T. Exp. Med., 96:531-48.

262 BIOGRAPHICAL MEM OIRS 1953 With I. Tamm. Fractional dilution procedure for precise titration of hemagglutinating viruses and hemagglutination-inhibiting antibodies. J. Immunol., 70:253-59. With D. A. l. Tyrrell. Neutralization of viruses by homologous im- mune serum. I. Quantitative studies on factors which affect the neutralization reaction with Newcastle disease, influenza A and bacterial virus T3. J. Exp. Med., 97:845-61. With I. Tamm and K. Folkers. Inhibition of influenza virus multi- plication by alkyl derivatives of benzimidazole. I. Kinetic aspects of inhibition by 2,5-dimethylbenzimidazole as measured by in- fectivity titrations..~. Exp. Med., 98:219-27. With I. Tamm and K. Folkers. Inhibition of influenza virus multi- plication by alkyl derivatives of benzimidazole. II. Measurement of inhibitory activity by hemagglutination titrations. J. Exp. Med., 98:229~3. With I. Tamm, K. Folkers, C. H. Shunk, and D. Heyl. Inhibition of influenza virus multiplication by alkyl derivatives of benz- imidazole. III. Relationship between inhibitory activity and chemical structure. l. Exp. Med., 98:245-59. 1954 Experiments on chemical alteration of virus infections. In: The Harvey Lectures, Series 98. N.Y.: Academic Press. With I. Tamm, K. Folkers, and C. H. Shunk. Inhibition of in- fluenza virus multiplication by N-glycosides of benzimidazoles. J. Exp. Med., 99:227-50. With F. W. Hartman and I. G. Kidd, eds., The Dynamics of Virus and Rickettsial Infections. (International symposium.) N.Y.: The Blakiston Co. With D. A. J. Tyrrell. Disruption of influenza virus. Properties of degradation products of the virus particle. l. Exp. Med., 99: 321-42. With T. Nadeje and J. Blum. An automatic tool for opening em- bryonated eggs. Rev. Sci. Instrum., 25:293-94. On the reproduction of influenza virus. Quantitative studies with procedures which enumerate infective and hemagglutinating virus particles. J. Exp. Med., 100:135-61.

FRAN K LAPPIN HORSFALL, JR. 263 With D. A. l. Tyrrell, I. Tamm, and O. C. Forssman. A new count of the allantoic cells of the 10 day chick embryo. Proc. Sac. Exp. Biol. Med., 86:59~98. Chemotherapy of respiratory viral diseases. (Special Reviews edited by Joseph Stokes, Jr., M.D.) Pediatrics, 13: 593-98. 1955 The inhibition of virus reproduction by chemical substances. In: Perspectives and Horizons in Microbiology: Symposium, ed. S. A. Waksman, pp. 152-67. New Brunswick, N.~.: Rutgers Univ. Press. With I. Tamm and I. C. Bugher. Ultracentrifugation studies of a urinary mucoprotein which reacts with various viruses. J. Biol. Chem., 212: 125-33. On the consequences of virus reproduction. Trans. Assoc. Am. Physicians, 68:54-63. Reproduction of influenza viruses. Quantitative investigations with particle enumeration procedures in the dynamics of influenza A and B virus reproduction. J. Exp. Med., 102:441-73. Approaches to the chemotherapy of viral diseases. Bull. N.Y. Acad. Med., 31: 783-93. Virus reproduction and virus disease. Can. Med. Assoc. I., 73:778-82. 1957 Interaction of polysaccharides and viruses. In: Polysaccharides in Biology: Transactions of the Second Conference, April 25, 26, 27, Princeton, NJ., ed. Georg F. Springer, pp. 41-113. N.Y.: Josiah Macy, Jr. Foundation. With I. Tamm. Chemotherapy of viral and rickettsial diseases. Ann. Rev. Microbial., 11: 339-70. Virus Diseases, Public Health Rep., 72:905-6. Virus neutralization tests: Implications and interpretations. Ann. N.Y. Acad. Sci., 69:633~3. 1958 Can viruses be managed? Proc. Amer. Phil. Soc., 102:442~7. Viral multiplication, in poliomyelitis. In: Papers and Discussions Presented at the Fourth International Poliomyelitis Conference (Geneva, 1957), pp. 335~1. Philadelphia: J. B. Lippincott.

264 BIOGRAPHICAL MEMOIRS 1959 With T. M. Rivers, eds., Viral and Rickettsial Infections of Man, ad ed. Philadelphia: l. B. Lippincott. Our new knowledge of viruses. Worldwide Abstr. Gen. Med., 2: 11-18. Inhibition of multiplication. In: The Viruses, Biochemical, Biologi- cal and Biophysical Properties, vol. 3, Animal Viruses, ed. F. M. Burnet and W. M. Stanley, pp. 195-224. N.Y.: Academic Press. Viral infections of the respiratory tract. (The I. Burns Amberson Lecture.) Amer. Rev. Resp. Dis., 80:315-25. 1960 Viral infection and viral disease in man. (Mayo Foundation Lec- ture.) Proc. Staff Meetings Mayo Clin., 35:269-82. 1961 On the unity of the sciences. Interreactions among the physical and biological sciences show that unification is progressive. Science, 133: 1059-60. Factors contributing to recovery from viral diseases. Can. Med. Assoc. J., 84:1221-26. Summary in poliomyelitis. In: Papers and Discussions Presented at the Fifth International Poliomyelitis Conference, Copenhagen 1960, pp. 425-26. Philadelphia: l. B. Lippincott. On the unity of the sciences. In: Medical Education and Medical Care: Interactions and Prospects. Report of the Eighth Teaching Institute, Association of American Medical Colleges. i. Med. Ed., 36:2~28. Extrinsic factors (environment). In: Congenital Malformations. Papers and Discussions Presented at the First International Con- ference (London 1960J, pp. 124-29. Philadelphia: I. B. Lippin- cott. Outlook for medical progress in this decade. A discussion of the probable effects of medical advances on longevity: Progress in cancer. Trans. Soc. Actuaries, 13:494-98. Dr. Leo Wade. Arch. Environ. Health, 3:496-98.

FRAN K LAPPIN HORSFALL, JR. 1962 265 Heritance of acquired characters. A unifying concept is developed in relation to the genesis of cancer. Science, 136:472-76. A look to the future. Cancer. Worldwide Abstr. Gen. Med., b: 13-14. Some new concepts in biology. Arch. Biochem., l(Suppl.~:63-67. 1963 Summary of the conference. In: Congenital Defects. Papers and Dis- cussions Presented at the First Inter-American Conference (Los ~lugeles 1962~' pp. 249-51. Philadelphia: J. B. Lippincott. Viruses and cancer. Acta Unio Int. Contra Cancrum, 19~1-2~:247~9. Role of infectious agents in the pathogenesis of neoplasia. In: Recent Progress in Microbiology, VIII International Congress for Microbiology (Montreal 1962J, pp. 458-66. Toronto: Univ. Of Toronto Press. A unitary concept of the origin of cancer. Bull. Un. Int. Cancer, 1 (1 August 1963~: 1. Foreword in honor of Thomas Milton Rivers. In: Perspectives in Virology III, ed. M. Pollard, pp. xvii-xix. N.Y.: Harper & Row. The role of viruses in relation to cancer in animals and man. In: Viruses, Nucleic Acids, and Cancer, Seventeenth Annual Sym- posium on Fundamental Cancer Research (Houston 1963J. Baltimore: Williams & Wilkins. Current concepts of cancer. Can. Med. Assoc. T., 89: 1224-29. 1964 Citation and presentation of the Academy Medal to Gilbert Dall- dorf, M.D. Bull. N.Y. Acad. Med., 40:267-68. Introductory and concluding remarks. In: Congenital Malforma- tions, Papers and Discussions Presented at the Second Inter- national Conference (New York 1963J, ed. M. Fishbein, pp. 3~. N.Y.: International Medical Congress. Some facts and fancies about cancer. (George Kober Memorial Lec- ture.) Georgetown Med. Bull., 18: 37-45. Committee on Science and Public Policy. Federal Support of Basic

266 BIOGRAPHICAL MEMOIRS Research in Institutions of Higher Learning. Pub. No. 1185. Wash., D.C.: National Academy of Sciences-National Research Council. The President's Commission on Heart Disease, Cancer and stroke. In: Report to the President: ~4 National Program to Conquer Heart Disease, Cancer and Stroke, vol. 1. Wash., D.C.: U.S. Gov- ernment Printing Office. 1965 Some facts and fancies about cancer. Perspect. Biol. Med., 8:167-79. The President's Commission on Heart Disease, Cancer and stroke. Report of the subcommittee on cancer. In: Report to the Presi- dent: A National Program to Conquer Heart Disease, Cancer and Stroke, vol. 2, pp. 103-17. Wash., D.C.: U.S. Government Printing Once. The President's Commission on Heart Disease, Cancer and stroke. Report of the subcommittee on research. In: Report to the Presi- dent: a National Program to Conquer Heart Disease, Cancer and Stroke, vol. 2, pp. 137-61. Wash., D.C.: U.S. Government Printing Once. Federal support of biomedical sciences. In: Basic Research and National Goals. A report to the Committee on Science and Astronautics, U.S. House of Representatives, by the National Academy of Sciences, March 1965, pp. 111-25. Thomas Milton Rivers. In: Biographical Memoirs, 38:263-94. New York: Columbia Univ. Press for the National Academy of Sciences. Fatti e fantasie sul cancro. Rassegna Medica e Culturale (Milano), 42:10-17, N.3. 1966 Cancer and viruses. Bull. N.Y. Acad. Med. 42:167-81. Leukemia in man and mouse. Acta Med. Scand. (Suppl. 445), 179: 304-11. Unifying concept of the origin of cancer. Med. Clin. of N. Amer. 50:869-74. Concepto unificador del origien deI cancer. In: Clinicas medicas de Norteamerica, Mexico, D. F. Editorial Interamericana, s.a., ed. D. A. Karnofsky and R. W. Rawson, pp. 869-74.

FRANK LAPPIN HORSFALL, JR. 267 Introductory remarks. In: Macromolecules and Cancer, Sloan- Kettering Institute for Cancer Research Symposium (New York 1965J. Cancer Res., 26:1957. Peyton Rous, Nobel Laureate 1966. The Rockefeller University Review, 4: 1~. Introductory remarks. Transformation mechanism. In: Subviral Carcinogenesis, ed. Y. Ito, 1st International Symposium on Tumor Viruses (Nagoya, 1966), p. 98. 1968 Immunology in 1968. (Presidential address before the American Association of Immunologists.) l. Immunol., 101:183-86.

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Biographic Memoirs: Volume 50 contains the biographies of deceased members of the National Academy of Sciences and bibliographies of their published works. Each biographical essay was written by a member of the Academy familiar with the professional career of the deceased. For historical and bibliographical purposes, these volumes are worth returning to time and again.

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