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i , : t 1960 REPORT of the SCIENTIFIC DIRECTO . CLARENCE COOK Li77LF„ 9e.D. ., ; ~ s ~ 0 ~ "~"" ~ 2•9 ~ ~ TOBACCO iNDU3TRY RESEARCH COMM ~ a H ~ l ~h

. i . , ~ Organization and Policy ~ The Tobacco Industry Research Committee is the sponsoring agency of a program of research into questions of tobacco use and health. It was organized in early 1954 by representatives of tobacco manufacturers, growers, and warehousemen. Soon after, the T.I.R.C. invited doctors and scientists well known for their work in cancer and other diseases to serve on a Scientific Advisory Board. This Board currently consists of nine scientists who maintain their respective institutional siflliationa. The Scientific Advisory Board has full responsibility for research policy and programming. As a Board it does not directly engage in research for the T.1.R.C. and the T.I.R.C. itself does not operate any research facility. Grants-in-sid for research are made by the Board to independent scientists who are assured complete scientific freedom in conducting their I research. They alone are responsible for reporting or publishing their find- ~ ings in the accepted scientific manner - through medical and scientific journals and societies. From the outset, the Tobacco Industry Research Committee has made clear that the object of its research program Is to encourage scientific study for facts about tobacco use and human health. Its position remains that research will help provide the knowledge about lung cancer and heart disease for a full evaluation of all factors being studied in connection with ~ these diseases. Grants recommended by the Scientific Advisory Board through 1960 ~~ have been made to more than 100 scientists in about 70 hospitals, universi- ties, tiea, and research institutions from funds that so far total $4,000,000 ~ appropriated by the T.T.R.C. A list of research projects supported by the T.I.R.C. is Included In this Report. Also included are abstracts of 47 research papers, acknowl- edging support by the T.I.R.C., that have appeared in scientific journals - since the 1959 Report and through October 1960. A total of 137 papers acknowledging T.LR.C. support have now been abstracted in the Annual Reports. 7tiwanrr V. Tl<arerxtsrr W. T. lioTT Ch.irman Exeeutive Director 00 TOBACCO INDUSTRY RF.SF.ARCii COMM1TiF.E ISO F...t 42nd 9tr.+et, New York 17, N.Y. 1960 REPORT of the SCIENTIFIC DIRECTOR CLARENCE COOK LPITLE, Sc.D.

TABLE OF CONTENTS s I Page Preface by Dr. C. C. Littk . . . . . . . . . . . . . . 5 Report by the Scientific Advisory Board . . . . . . . . . . R Results of Research Cancer Research . . . . . . . . . . . . . . 14 Human Lung Studies . . . . . . . . . . . . . 17 Heart and Circulation . . . . . . . . . . . . . 19 Psycho-physiological . . . . . . . . . . . . . 20 Tobacco Chemistry . . . . . . . . . . . . . . 20 Abstracts of Report Cancer Research . . . . . . . . . . . . . . 24 Human Lung Studies . . . . . . . . . . . . . 33 Heart and Circulation . . . . . . . . . . . . . 34 Psycho-physiological . . . . . . . . . . . . . 46 Tobacco Chemistry . . . . . . . . . . . . . . 46 Other Studies . . . . . . . . . . . . . . . 52 Titles of Previously Published Abstracts . . . . . . . . . . 55 Recipients of Grahts . . . . . . . . . • . . • • • • 61 ~ F~+ ~.G

SCIENTIFIC ADVISORY BOARD to the Tobacco Industry Research Committee KENNETH MERRILL LYNCH, M.D., Sc.D., LL.D., Chairman Chancellor Medical College of South Carolina Charleston, South Carolina RICNARD J. DING, M.D. Professor and Chairman, Department of Medicine Wayne State University College of Medicine Detroit. Michigan McKEEN CATTELL, Ptr.D., M.D. Professor Emeritus of Pharmacology Cornell University Medical College New York. N. Y. LEON O. JACOBSON. M.D. Professor of Mrdicinr'. University of Chicago Director, Argonne Cancer Research I lospital Chicago, Illinois PAUL KOTIN, M.D. Paul Peirce Professor of Pathology University of Southern California, School of Medicinp Los Angeles. California CLARENCE COOK LITiT.E, Sc.D., LL.D., Ltn.D. Scientific Director, Tobacco Industry Research Committee Director Emeritus, Roscoe B. Jackson Memorial Laboratory Bar Harbor, Maine •7 STANLEY P. REIMANN, M.D., Sc.D. r! Director Emeritus, The Institute for Cancer Research ~ Philadelphia, Pennsylvania WILLIAM F. RIENHOFF, Jtt., M.D. .1 swiate ProJcssor of Surgery Johns Hopkins University School of Medicine Baltimore. Maryland EDWIN B. WILSON, Px.D., LL.D. Professor Emeritus of Vital Statistlcs Harvard University -7 1 Cambridge, Massachusetts iV ~ ROBERT C. HOCKETT, Ptt.D. J. MORRISON BRADY, M.D. O Associate Scientific Director Associate Scientific Director Preface The year 1960 was one of great interest and activity for the Scientific Advisory Board to the Tobacco Industry Research Committee. As general lines for development of promising research have become evident from accumulated experience, a program consistent with them is being rapidly evolved. During the year, the T.I.R.C. responded to a request from the Board for additional funds for research grants by increasing annual approprlations to $800,000. These additional funds will be for Zupport of further study in the fields of viruses, psychaphysiological traits (constitutional ditTer- ences), previous chest and lung infectiona, bio-assay, and tissue culture. Causation Theory of Smoking Unprotvd The continued failure of evidence which k qualitatively different or of increased significance to appear leaves the causation theory of smoking in lung cancer, heart disease, and other ailments without clinical or experi- mental proof. Meanwhile, evidence of the complex factots involved in the origin and nature of these diseases continues to increase in quantity, depth, and scientific significance. The result ia that the tobaxo theory is rapidly losing much of the unique importance claimed by Its adherents at its original announcement. It has not retxived definitive support In the clinie and laboratory. One Hnrd Fnct: Much More Mnrt be Foauad Out With all that we have learned in the laboratories and the elinies, work- ing with animals and chemicals and people, exploring a variety of avenues and approaches, the one hard fact that we must face up to is that there is so much more to find out. We will not find out from over-aimplifled and perhaps superfieiat conclusions as to causation. Such an attitude would only stifle or delay needed research to find the basic origins of lung cancer and cardiovascular diseases, which are most powerful, diversified and deadly enemies to our well-being. Nor will they be solved by public pronouncements or by tesolu- tions or by review committees that concern themselves solely with sugges- tive or incompiete data. 'Ifie answers will come only from the accumulation and coordinathat of creative knowledge acquired In many 8elds of endeavor after patieM, careful study.

.~ ~ ~ i• Statiairnt nnta Require Studl.. Jn Other Area. The members of the Scientific Advisory Board have repeatedly made clear they feel that the statistical data thus far advanced to show a statistical association between smoking and various diseases are sufficiently suggestive and important to justify and, indeed, to require a great deal of further research in other major areas. This is necessary in order to evahfate the existing data accurately and to make possible a more scientific definition and analysis of the problems involved. In spite of these often-repeated statements, there apparently still exist misunderstandings and misstatements of our attitude in this matter. It may be of value, therefore, to suggest certain steps in research which can be taken to provide evidence that will have a higher degree of scientific value and that should help in the necessary definition and analysis to which reference has been made. Re.eareh Stepa Sug6e.ted Fust, further efforts should be made to see whether cancer can be in- duced in animal tissue by the direct application of whole smoke instead of by artificially prepared condensates of smoke. Second, epidemiologieal data should be obtained by direct clinical observation rather than by questionnaires and hearsay opinion. In such longitudinal clinical studies, factors and habits other than smoking should also be included. It is as important to know, for exampie, why the over- whelming majority of heavy cigarette smokers do not develop lung cancer as it is to know why the comparatively small percentage of smokers do. Third, pathologists need to make concerted efforts to improve and agree upon criteria for classification of human lung tumors into types such as adenoma and squamous cell cancer so that studies of relative rates of incidence and of possible environmental and other influences on such rates could be made more meaningJaf. Such research is entirely possible. It is admittedly time-consuming and di/ficuit but it is a eecessary steppingstone toward a level of knowledge which must be attained on the road to solution of the problems that may be involved in tobacco use in relation to health. Report Ly the SeJentifie Adoi.ory Bonrd - 'This year, for the first time lince its formation fn mid-1954, the Scientific Advisory Board made a formal report to the Tobacco Industry Research Committee. This report, which begins on page R, considers the changes that have occurred In the last seven years in the status of knowledge of the relationship of smoking to health, reviews the Board's scientific pro- 6 gram, and discusses the needs and directions for further research. The Board states in its report that so far as a final solution of cancer and heart disease is conarned, scientific honesty requires acknowiedgment that, in the absence of greater knowledge of the fundamental processes involved, a simple answer to what are not simple questions is unlikely in the near future. The Board has been fortunate in maintaining the same persortnel who joined it seven years ago. Recently, however, Dr. Julius H. Cotnroe, Jr., a member of the original Board, found that after moving from Pennsylvanip to California, the combination of increased professional responsibilities and geographic distance was making it impossibk for him to attend Board meetings in the east with the regularity he desired. He has, therefore, re- signed from active membership while retaining the same active interest in the Scientific Advisory Board's program and the willingness to help it in an advisory capacity. Dr. Comroe's loss will be a very real one, for his knowledge and originality are great. Appreciation also is expressed for the constructive contn'butions of T.I.R.C. grantees and scientific consultants, and of participants in the con- ferences sponsored by the Scientific Advisory Board. The members of the T.I.R.C. also are to be commended for their eontinued, generous support of the research program, and for enabling those of us responsible for the program to work with the most complete freedom. Their trust in the mem- bers of the Scientific Advisory Board is stimulating and warming. C. C. LiTTLE Scientific Dirrctor 7

4 ~ n ~-i X ..3. ~ 0 0 ~ Report by the SCIENTIFIC ADVISORY BOARD to the TOBACCO INDUSTRY RFSF,ARCIi CnMMITTI?F At the end of its first six years of operation, the Scientific Advisory Board deems it advisable to take stock of the changes which have occurred during this period in the status of our knowledge of the relationship of smoking to health, to review its scientific program, and to consider the needs and direction for further work. At the time the Board was established, epidemiological studies report- ing an association between cigarette smoking and cancer of the lungs were being extensively publicized. The hypothesis that this relationship might represent a causal one was based in part upon experimental studies in which it was reported that the prolonged application of certain cigarette smoke condcnsates to the skin of the mouse was capable of producing malignant changes. It is from this perspective that advances in our understanding of the problem during the past six years must be evaluated. Major effort has been devoted to the independent investigation of the two great fields of cancer and of cardiovascular disease. There have been definite advances in knowledge and improvements in technique. So far at concerns a final solution of the problems, scientific honesty requires ac- knowledgment that, in the absence of greater knowledge of the fundamental processes concerned, a simple answer to what are not simple questions is unlikely in the near future. Expanded Rracarclr Offers Rest Ilope Continued efforts to stimulate the broadening and deepening of re- search in all areas where knowledge is deficient offer the best hope for thc future. Much of our research program has been fundamental or basic in character - an area where progress is less certain but the possible rewards greater. This has been achieved without neglecting clinical problems and others having practical aQplieation. % Naturally, it takes time for a venture of this sort to get under way, but it is noteworthy thatga nts have been made to more than 100 scientists in about 70 medical schools and other research institutions throughout the country, representing an overall financial support of nearly $4,0t)D,t>D0. 8 Already approximately 137 eontribvtionspreaenting the result< of .avr)<' done under this support have been published in the scientifie literatnre. Even though it must be admitted that the effort thus far has barely scratched the surface, excellent scientific studies have been reported, and it can confidently be assumed that the facts rovealed will ultimately con- tribute to the solution of the broad questions which concern us. But per- haps the most significant development has been the general recognition that we do not yet have the answera, that an association between the extent of tobacco use and the incidence of lun¢ cancer does not prove a causal rela- tionship, that experimental verification is essential and that there are a number of other factors which need to be considered. We are not satisfied to let the problem rest with statistical reports suggesting that heavy smmoking increases the risk of cancer of the lung; we arc interested also In knowing why the overwhelming majority of heavy smokers do not contract the disease despite their smoking. We are also vitally intercsted in the meaning of the results, derived from the same data, that only a small fraction of the reported excess deaths in the heavy smoking group is attributable to eancer of the lung. Lung Pathology Study of 3,000 Cases In reviewing the results of the scientific program, a few specific con- tributions will be selected which are illustrative of the various litxs of research under way and which have contributed to a change in viewpoint. A cooperative study of lung pathology on autopsy material in 3,000 cases from 12 hospitals is notable in several respects. It revealed wide differences in interpretation of the same slides by different members of the group. It demonstrated a high incidence of epithelial changes in the bronchioles, even in the younger age groups and, while the incidence of hyperplasia and metaplesu was somewhat gteater in those with a history of heavy smoking, "carcinoma-in-situ^ was seldom seen. An experimentsl study in which mice were exposed to cigarette smoke daily resulted in chronic bronchitis in a variable proportion of mice in each group with epithelial prolifieration which in some instances resembled "carcinoma- in-situ;" but never progressed to carcinoma and reverted to wxmnl when exposure to smoke was discontinued. These studies werc significant (1) in demonstrating the need for further study of tissue patholog7 with reference to the role of infection and the uniformity of interpretatton, and (2) in bringing into question the validity of designating hyperplastic changes in lung epithelium as precancerous. A large number of different biologkal systems, including moust-skin painting, have been tried in the attempt to establish some relative potency rating for cigarette smoke condensate on a rational acale of carcinogenic activity. The smoke condensate has proved to be inactive in most of these tests, and in several cases the tnethods hare been found unsatisfactory for the intended purpose. No definite evidence exists that the responses of inted mouse skins are interptetable indkators of carcinogenic haatds Kor the human lung. Conaequently, we hare selected a few of the most promising bioeasay techniques for Mrtltet etudy and development in the hope of perfecting a more rapid and reliable assay. Though it cattnot be 9

I said that a relative potency rating for cigarette smoke condensate has yet been achieved in any quantitative sense, the extensive assay experience has created the general impression of such feeble activity as to shift the focus of attention to other plausible mechanisms whereby tobacco smoke might contribute by indirect means to the pathogenesis of cancer. Studies of the influence of smoking on gastrointestinal function have shown that there is no significant eRect, either in normal persons or in ulcer patients, on the composition, amounts or properties of gastric secre- tions as indicated by eight measured parameters. These findings suggest that the reported statistical correlation of cigarette smoking and peptic ulcer may reflect association between the ulcer-prone temperament and a tendency to smoke rather than a causal contribution of smoking to ulcer genesis. The cardiovascular research program has shown that the response in man or the peripheral vascular system to nicotine is usually, but not always, a diminished blood flow in the skin of the extremities, while dila- tion occurs in the deeper (issuea. Changes in the coronary artery circula- tion, when nicotine absorption is sufB~cient, are in the direction of increased blood flow sufficient to meet increased oxygen demand attending increased muscular work. There is some indication that these responses may be modified in the prc sence of atherosclerosis. Measurements of cerebral blood flow in healthy persons showed no significant changes induced by smoking. DiJf erences Reported Between Smokers and Non-Snrokers Evidence has been collected to show that smokers, especially heavy smokers, differ in temperament and personality from light or non-smokers. More rtcently, an association between smoking patterns and body build has also been demonstrated. These obser.ations conform with earlier studies on twins, and lend support to the concept that at least some part of the associations of smoking with particular disesses may reflect a common con- stitutional predisposition rather than direct contribution of smoking to causation. Studies of pultnonary physiology as affected by smoking have shown no consistent significant changes In blood gas exchange at rest or after one-minute step-up exereise, but some fa11 in oxygen uptake during tread- mill exercise after smoking. Pultttonary compliance has been variously re- ported as decreased after smoking and also as unaffected in normalpe rsons. /n emphysema and chronic bronchitis the changes induced by amoking are greater. Long-time smokers are reported to show somewhat increased residual lung volume, and bodr pkthysmograph measurement indicates somewhat increased airway resistance following smoking, an effect not ,Pue to nicotine. A considerable number of basic studies have been done which repre- sent important contributions to our research program, but which will not be described here In detail. Sotne of these are in the general area of chemical srthesis and breakdowo of the constituents of tobacco including methyla- tion reactions, metabolism of pyridine components, enzymatic fixation of CO,. and the polyphenol content of leaves. Other studies have concerned 10 fundamental aspects of catcinogenesis, and Include observations on 4h. early changes in the lungs of tumor-bearing rats, the cytology and nuckr deoxyribonucleic changes of skin and lung epithelium exposed to eucinc gens, and the action of carcinogens on cultures of human lung tissue. With T.I.R.C. support various activities, designed to promote the ot jectives of the Scientific Advnory Board other than through research grant• have been initiated. These inelude thepteptretion of a "standard" eigaretr smoke condensate produced under conditions of natural smoking, thu making available to grantees a uniform product. To overcome the shortag of inbred strains of mice needed in the research program, a grant was mad to expand breeding facilities. Informal ConJerences to Exchanae Ideas, Knowledge Por the purpose of promoting the exchange of Ideas and to tvaluete the status of existing knowledge, a number of Informal conferences o workers in specific topics have been held. A conference of pathologist% meeting to consider the significance of changes in the lnng epithelium, ha, led to a cooperative study, tnentioned elsewhere In this report, which ha- been the subject of several additional cottferenas. 'hsree conftxencea con cerned with the cardiovascular effects of nicotine and smoking culminated ir the organization of a thtre-day public symposium on the subject hetc under the auspices of the New York Academy of Sciences in March 1960 In the field of tissue culture, the topic of two informal oanferences, there was recognition of the shortage of trained personnel and provision has been made to enable several laboratories to train additional workers in the spe- cialized techniques required. Other confetences, all of which have contributed to the scientific pro- gram of the Board, include two on bioassay of carcinogenic compounds, one on the role of Infections in the genesis of lung ancer, and two on the bearinf of constitutional or prychological diffetettces on smoking habits. The T.I.R.C. has also provided funds to make possible a symposium on at- mospheric factors in disease held lanuuy 1960 at the niversiry oI Cali- fornia under the titk, "'17te Air We Bteathe " With the object of encouraging able sttxfenb to embark on a career 1n science, an annual grant has been made available to each medical school in the United States to provide a fellowship for work during the summer months or other holiday period, unrestricted as to subject. Another significant contribution has been a grant to make possible the preparation of a book on the biologic effects of tobacco and nicotine which will be published in the near future. This large volume, based on a very complete review of the world's literature, should serve as an invaluable source book for information on the sub}ect. Many Research Areas Being Studied The Scientific Advisory Board has given much consideration to the direction and emphasis of its reesearchproga m as it can tnost profitably be developed in the years immediately ahead. In most instances studies now under way must be continued but the Board Is exploring and, in some cases, plans are wcll along for expanding, certain lines of work and adding others.

Those receiving consideration are: n ~--/ ~ / 1. The possible role of previous infections or injuries in the origin of lung cancer. 2. Extension of bioassay methods for carcinogenic activity. 3. A comparative study of the activity of, pipe, cigar and cigarette tobacco smoke condensates produced under identical conditions. 4. Improvement in diagnosis of early lung lesions. 5. The possible role of viruses in carcinogenesis. 6. The question of threshold dose and latent time in chemical car- cinogenesis. 7. The biological activity of smoke in terms of the relationship be- tween its various components with a view to throwing light on possible anticarcinogenic influences of analogues. R. Extension of the tissue culture technique for studying normal and abnormal growths, including utilizing the newly-perfected syn- thetic media. 9. Further studies of the influence of smoke and other atmospheric pollutants on the lining of the bronchi, including the activity of the cilia. 10. Epidemiologieal studies in relation to ethnic, social, ecologic and cultural differences. 11. A pathologic study of urban and rural populations. 12. Composition of smoke with regard to particle size and concentra- tion and irritant action of components, singly and combined. 13. Mechanisms of particle absorption and transport by respiratory cells, of normal and altered mucous secretion, of normal and al- tered ciliary activity, and of normal and altered cellular regen- eration. 14. The role of the autonomie nervous system in modifying the total host responae and that of the respiratory epithelium. 15. Studies of human twins for the purpose of analyzing hereditary and environmental factors in diseases. 16. Possible changes in mouth and throat microorganisms in smokers. 17. Cardiovascular responsn to smoking in subjects with athero- sclerosis and other disorders, including a direct study of retinal vessels. 18. Influence of smoking and nicotine on the composition and prop- erties of blood. 19. Comparison of the psychological and physiological effects of smoking with those of tranquilizers. 20.- The question of possible allergic reactions to tobacco smoke. 21. A eomQarison of the physical, emotional and psychological char- acteristrcs of smokers with non-smokers. 22. The effects of stopping smoking. : T.I.R.C.'a Support Appreciated In concluding this report, the Scientific Advisory Board wishes to record its appreciation to the Tobacco Industry Research Committee for providing large sums for research and for approving all its recommendations without question. It is spptoprsate to make brief reference to the Board's experience since its estab rsl' hment. The Board has held meetings at least quarterly since its organizatfon, and has awarded considerable money to inrestigators, but this prrseat com- munication is the first report It has made to Its sponsoring organization and this without request. To sct forth an evaluation of aocompilshment made by this apQro.ch to the subject, while the credit does not accrue to the Board or Its memben, certainly one of the most significant occurrences Is that a major business industry has organized Itself to determine so far as possible what, if any, effect its products have on the health and well-being of its customers. We must continue to search for scientific talent dedicated to the seeking of knowledge and support it fully so that It mq be freed of inSeenrity which may hamstring it. Vve_ must continue to let k be known that we are In that search, and applicants for projected research should be supported if their ideas are promising and their opportunities good. We must continue efforts to stimulate broadening and deepening of reaeanch in all of the areaa where knowledge is scant. We must not be disturbed by Inconclusive and/or faulty reports, nor react a¢sinst them defensively. We must continue to promote trne basie te+eateh In the Intmeilular processes of life and in the multicetlular livinE~orgunization even though, in some instances, this will have no obvious or immediate connection with the practical question of tobacco and health. As the tobacco industry continues ita sapport of the search for truth and knowledge, it must recogtdze, as is always the case In true scientific research, there can be no promise of a qnick answer. The important thing is to keep on addin6 to knowledge until the accumulative af cts pnovide the basis for a sound conclusion. Kenneth Merrill Lynch, M.D., ScD., LL.D., Clw.drnran Richard J. Bing, MD. McKeen Cattell, Ph.D., M.D. Leon O. Jacobson, M.D. Paul Kotin, M.D. Clarence Cook Little, Sc.D., LL.D., Lltt.D. Stanley P. Reimsnn, M.D., Sc.D. William F. Rienhoft, Jr., M.D. Edwin B. Wilson, Ph.D., LLD. 13 12

Results of Research The constantly growing number of published papers on studies sup- ported by the Tobacco Industry Research Committee is a measure of the progress of the research program. These papen, which totaled approxi- mately 137 by the end of October 1960, are abstracted individually or listed elsewhere in this Report. An additional 22 papers, given t a cardio- vascular conference held during the year, were subseqoently published and are listed on page 22. In this section are summeries of the findings and major points in several important fields of study. At times the summaries may cover re- search not yet published in full. Not all the studies in progress or com- pleted are discussed here. These summaries are: I. Cancer Research; 11. Human Lung Studies; tif. Heart and Circulation; iV. Psycho-physiological, and V. Tobacco Chemistry. I 1. Cancer ReaeQrch Several studies on the effects of tobacco smoke and of smoke con- densates on animal tissues have been reported during the past year, as well as a number of collateral studies in the cancer field which did not involve the use of tobacco. Tobacco smoke condensates in liquid petrolatum were introduced Into the trachea of young adult ducks daily over long periods of time and en- compassing up to 130 injections. No changes suggesting neoplasia de- veloped, though some acute and chronic reactions occurred both among treated ducks and in some untreated birds as well as in some receiving only petrolatum. As one of a series of control studies, ducks were also given methyicholanthnttte in several forms by the oral route. Gastrointestinal system tumors were not produced by these means. An extensive study was completed to determine and compare the effects of various inhaled gases and aerosols on the activity of the cilia of bronchial epithelium and the rate of flow of the mucous stream. Various 01 inhaled agents, inchtding tobacco smoke, were found to be capable of 2V temporarily inhibiting ciliary activity and delaying movement of the mucous blanket. The correlation of there effects with morphologic changes of the respiratory epithelium was also begun. These observations have emphasized the need for further work to evaluate the functions of mucus as a protective material, the dependence of its functions upon chemical and physical com- positions, and the faetors which can modify composition. The mechanisms that influence ciliary activity seem also to call for.further elucidation, a. - does the overall rok of the ciliary-mucus system in protection against extraneous inhaled carcinogenic agents. New studies have been authorized ' along such lines and an investigation of the effects of air ions upon ciliary behavior has been undertaken. Smoke 11e.1No F,AKt on Moa.e L.nR Adenomaa Two scientists, reporting further on their tobacco smoke inhalation itudies, found that the incidence of grossly visible lung adenomas in female CF' mice is unaffected by prolonged smoke exposure. Collateral studies have included extensive observations of the chrom- osome numbers and ploidy of human and animal cells cultivated In vitro, and observations on the responses of mouse and human cells cultured irt vitro to acetaldehyde exposure. Another researcher has observed the sensitivity of the mouse fore- stomach to carcinogenic hydrocarbons painted on the skin or administered orally, and has suggested the utilization of this sensitivity as a basis for a bioassay technique. An experiment has shown the enhanced ability of tissue sBces from several organs of rats bearing the Walker or Jensen tumor to Incorporate labelled thymidine into deoxyribonucleic add (DNA). Another investigator has reported detailed pathologic studies of the interrelations between inflammatron, keratinization and glycogen deposition in alveolar mucosa and gingiva. Con/ervnce on Celt and Tissue Cadtrre The T.I.R.C. has been supporting raearch in the field of tissue culture for some time. The work has included attempts to establish strains of dif- ferent human tissues, especially lung tissues, so that responsa of such tissues to carcinogenic and other agents could be observed. It is hoped that this area of endeavor will provide new and helpful information about the mechanisms of carcinogenesis. orantees and other scientists working In cell and tissue culture or related fields of research met for a discussion on May 24, 1960. Among those present, in addition to members of the Scientific Advisory Board, were the following: DR. PHILIP COOPER, DR..IVY OOLDRINO. MR. MORRIS KLEIN. Albert Etrntetn ColtM of Medicine, New York. N. Y. DR. OEOROE O.OEY, DR. MARY REED. MISS HEDA t.INDf'tI, Finney-Howell Caneer Research Laboratory. Johns tlorkirn Hospital, t3dthrore, Maryland DR. CECILIE LEUCHTENI3EROEk; dtlkren'a Canerr Re.xsrch Foundation, 13oaoo, Massachusetts 1S

f DR. ALVIN S. LEVINE. indiana University Medical Center. Indian- polit, Indiana DR. BILL P. MADUROS, The Hektoen )nstitute (or Medical Re- search. Chicago, Illinois DR. DONALD M. PACE, Institute for Cellular Research, University of Nebrnka, L'ntcoln, Nebraska DR. O. 1. POLLAK. DR. TATSUO KOKUBU, MRS. PATSY S. MORROW. Dover Medical Research Center. Inc.. Dover. Detaware DR. C. M. POMERAT', DR. A. AWA, DR. Y. OIINUKI. The Uni- versity of Texas Medical Branch. Galveston. Texas DR. ALAN S. RABSON. Pathoto=ie-Anatomy Department, National Institutes of Heakh, Betheada, Maryfand DR. SARAH I? STEWART, Laboratory of Biology, National Cancer Institute, Bethesda, Maryland DR. CHARifY WAYMOUTH, Roscoe B. Jackson Memorial Labor- atory, Bar Harbor. Maine VtroloRy ConJerence On May 25, 1960, an Informal eonference covering the subject of viruses and their possible relationship to human cancer was held. Discus- sion centered on the present state of knowledge concerning the role of viruses in cartinogenesis, and promiaing areas for future research. Members of the Scientific Advisory Board attended the session, as did the following recipients of T.LR.C. grants and others doing research in the field: DR. THOMAS F. ANDERSON, The Institute for Cancer. Research. Philadelphia, Pennsylvania DR. PHILIP COOPER. DR. IVY OOLDRINO, Albert Einstein Col- lege of Medicine, New York, N. Y. DR. GEORGE OEY, DR. MARY REED. Vinney-Howell Cancer Re- search Labontory, Johns Hopkins Hospital. B.Itimore, Maryland DR. CECILIE LEUCHTENBEROER, Children's Cancer Research Foundation, Boston, Manachuretta DR. ALVIN S. LEVINE, Indiana University Medical Center. lndian- apolia, Indiana DR. BILL P. MADUROS, The tfektnen In.tltutr for Mrdieal Ra aeareh, Chicatto, Illinois DR. CIIRI,STOPIII?R M. MARTIN, Divi.ion of Infertiou. Dlaa.e., Seton tLtl College of Medicine. Jersey City. New Jersey DR. C. M. POMERAT', The University of Texu Medical Branch. Galveston. Texas DR. ALAN S. RABSON, Pathologk-Anatotny Department. National Institutes of Health, Betheada, Maryland DR. SARAH STEWART, Laboratory of Biology. National Cancer lnstitute, Bethesda, Maryland DR. HOWARD M. TEMIN, Division of Bio1o6Y. California Institute ' f T h l ~ o ee no ojy, Paaadena, Catiforoia DR. CHARITY WAYMOUTH, Ro.coe B. Jackson Memorial f.abor- ~ atory, Bar Harbor, Maine ~•Now at Pa.adena (Gl.) Foundation for Medint Research. 16 I I Even prior to this confertner, ittcreased emphasis h>,d bren rlnerd upon research to evaluate the possible role of viruses in carcinogenesis. The study of virus infections of the respiratory aystem of mice in producing dysplasias either with or without smoke inhalation had been undert*tken as an extension of the smoke inhalatbn studies. Investigations of the Inter- action of polynuclear hydrocarbons attd of trace metals with .irvhave also been sponaortd. Sympoalum on "TAe Air i~tr ~ItrMtalM" On January 16-1d, 1960, a adbferentb /rft held at San Pranclec+o on "Man and His Envi:ottment: 'iTte Air We Bteathe" under the oombh+rJ auspices of the University of CL1lfotni! Sehool of Medicine and Unlver+ity Extension-Department of Contlnning Education In Medicine and Health Sciences. Partial financial atrsitttenoe for the meeting was contributed under a grant approved by the Sckntific Advifory Board. The three-day session t:mtsidAted the en.lrontttent tts >t wfiole and from the widest biologic point of view. SCiettth>ts came from the United States, England, Wales, Pbru, and New Zealand, and many disciptlnes were represented. Among those preseot were phyaicitun, pathobgists, pltyablo- gists, ecologists, town platntets, and entineerl, The problem of air pollution appeared to be nppermos t (n.the minds of virtually a11 the part3cipants, md the anb}eet of smog was atreaaed in many of the paptxs. The tdatWcd ariatytfb of tobaoco in telatbe to hmg cancer was the theme of tl ~aCQtadbe by twtf t+deetlats whlt oontrasda=.kws. One significant tt~port wM nu~e 6~ tt Nbiv Zealand at9etttist who dis- cussed his findings on hntt cancbt tA" Eftllahmen who mlgated to New Zealand as compared with ttatMe of tbat covntry. Both =roupa Md the same constitutional or hereditary tnali#up, the same way of life, and similar eating and ainoking habits. But the former came from stttog-f111ed industrial atmosphere into an unpolluted atmoapherc. 71x Incidence of lung cancer was 30 percent higher among the 1mm1- grants generally than among the native-born white residents. But Immigrants who came to New Zealand relatively late In life, after spending 30 or more years in England, had a lung cancer Incidence about 75 percent above that for New Zealanden of the same age. The Proceedings of the symposium are expected to be published shortly. 1t. Hutnatz Lung Stt!ititea The need for tnore adequate and comptehensive methods for measur- ing and evaluating human lnng function has been rr,cognized as one means of Improving the study of chronic and progressive lung diseases. A T.I.R.C. 17