Cancer Research in the United Kingdom: Guest Editorial

CANCER RESEARCH

VOLUME16 OCTOBER 1956 NUMBER9

Cancer Research in the United Kingdom

GUEST EDITORIAL

Cancer research in the United Kingdom has its morphism;" other subjects under investigation roots in the traditions of British medicine, surgery, include mammary cancer, fowl leukosis, and en and pathology in the 18th, 19th, and early 20th docrine and azo dye carcinogenesis. A later de centuries. For practical purposes, it may be said velopment in the history of the Fund has been to have begun when Percivall Pott (1713-88), the establishment of a clinico-pathological labora surgeon to St. Bartholomew's Hospital, who was tory at Lincoln's Inn Fields, under the direction aware of Ramazzini's accounts of the morbi arti- of Geoffrey Hadfield, whose recent work on urinary ficum, described the particular form of cancer mammotrophin has evoked so much attention. occurring in chimney-sweeps (cancer scroti, in Not long after the establishment of the Imperial Chirurgical Observations, 1775), and traced it to Cancer Research Fund came the foundation in contamination of the skin by soot. Over the next 1909 of the Research Institute of the Royal Cancer century, numerous classical contributions to the Hospital. First directed by Alexander Paine (of study of this and many other aspects of the cancer Poynton and Paine's Streptococcus rheumaticus problem were made through the work of such men fame), its early staff included such notable figures as John Hunter, Hodgkin, Earle, Astley Cooper, as Jack (later Sir Jack) Drummond and Casimir Hughes Bennett, Paget, Joseph Bell, Butlin, and Funk, then working, respectively, on the amino Bland-Suttonâ€”to name but a few. About the acid composition of tumors and on "vitamines," century's turn, it became apparent to various which term the latter had coined. It is perhaps Fellows of the Royal College of Physicians of not without significance that so much of this early London, and of the Royal College of Surgeons work lay in the field of nutrition. Paine was suc of Englandâ€”wise in their day and generationâ€” ceeded by Archibald Leitch, who inaugurated the that effort should not be confined to clinical medi Institute's continuing interest in chemical car cine and surgical pathology alone, but that a new cinogenesis, later to be developed to such purpose attack was needed through the experimental by his own successor, Professor (now Sir Ernest) method. Thus came about the foundation in 1902, Kennaway, and by J. W. Cook and their school. under the aegis of these bodies, of the laboratories The Institute, together with the research units of of the Imperial Cancer Research Fund. There the Physics and Radiotherapy departments of the very soon followed, through the brilliant director Royal Cancer Hospital (now under the direction ship of E. F. Bashford and the work of a team of Professor W. V. Mayneord and Professor D. W. of pioneers including J. A. Murray, W. Cramer, Smithers, respectively) was soon recognized as a M. Haaland, B. R. G. Russell, and (for a time) school of the University of London. In 1939 re- Woglom, a formidable contribution to our early designated the Chester Beatty Research Institute knowledge of the biological characteristics of the in recognition of a great benefactor, it now, to cancer cellâ€”knowledge enshrined in what Peyton gether with the same research units, constitutes Rous has called the wonderful "powder-blue the Institute of Cancer Research: Royal Cancer volumes" of the Fund's Scientific Reports. The Hospital, as an Institute of the British Post Fund's experimental laboratories are directed at graduate Medical Federation and a University the present time by James Craigie, who with great School, financed however mainly through the technical prowess has made an outstanding con Medical Research Council. tribution to problems of the survival of tumor A new development took place with the in cells in vitro, with special reference to "para- auguration, in 1923, of the British Empire Cancer

821 Thi, One

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Campaign. Primarily a fund-raising body, the continues his investigations of the role of protein Campaign, guided by its Scientific Advisory Com binding and of the importance of the sub-epithelial mittee, annually distributes support to a wide tissues in the induction of cancer of the skin; while range of University medical school and hospital at the London Hospital, Salaman and Roe are laboratories and to individual workers, engaged pursuing their study of the initiating and promot upon almost every aspect of cancer research and ing stages, in extension of the general theory including, for example, the research laboratories developed by Berenblum at Oxford several years of the Middlesex Hospital (comprising the Bland- ago. At the Institute of Cancer Research much Sutton Institute of Pathology, the Courtauld attention is still being given to the biological Institute of Biochemistry, the Barnato-Joel labora alkylating agents as carcinogens and mutagens, tories, and the Meyerstein Institute of Radio through the work of Bergel, Ross, Elson, Fahmy, therapy, under Professor R. W. Scarff, Sir Charles RÃ©veil,Alexander, and many others, with the Dodds, Professor J. E. Roberts, and Professor provisional conclusion, similar to that reached B. W. Windeyer, respectively), the Institute of for the azo carcinogens by the Millers at Madison Cancer Research: Royal Cancer Hospital, St. from an altogether different approach, that these Bartholomew's Hospital, Mount Vernon Hospital agents may operate by inducing a kind of somatic and Radium Institute, Westminster Hospital, mutation by loss. As to the carcinogenic amines, Guy's Hospital, the London Hospital, St. George's the hypothesis of Clay son, that the carcinogenicity Hospital, Marie Curie Hospital, St. Mark's Hos of amines depends upon more rapid conversion to pital, the Hospital for Sick Children, the Royal Col o-aminophenol derivatives, continues to be tested; lege of Surgeons of England, the Yorkshire Council, and the redevelopment of the technic of direct the North of England Council, the Birmingham vesical implantation of carcinogens, by Bonser and Branch, the Cambridge University Research Jull at Leeds, has been of great service in the Centre, the Oxford Cancer Research Committee, special case of cancer of the bladder. It should the Royal Beatson Memorial Hospital (Glasgow), be noted that substantial contributions to our the Christie Hospital and Holt Radium Institute knowledge of the carcinogenicity both of the aro (Manchester), Bristol University Cancer Research matic amines (especially of p-xenylamine and its Committee, and the Nottinghamshire Branch. derivatives) and of the alkylating ethyleneimines Thus, the Campaign's Annual Reports provide as have been made by Walpole and his associates good a conspectus as can anywhere be obtained, in the laboratories of Imperial Chemical Industries of cancer research in the United Kingdomâ€”and at Manchester. In spite of the great difficulties also in the Empire, through the reports from in deciphering their mode of action, the carcino Canada, Australia, New 'Zealand, South Africa, genic hydrocarbons themselves are by no means and elsewhereâ€”over more than 30 years. Apart forgotten: their metabolic transformations con from its main work (which resulted in the pro tinue to be studied by Boyland and his group at vision of some Â£400,000last year), the Campaign the Institute of Cancer Research and by Chalmers is also responsible for an Animal Supply Unit at the Royal Beatson Memorial Hospital in (in the University of Edinburgh), and for a Re Glasgow, among other centers ; and studies of the search Unit in Radiobiology (at Mount Vernon crystallographic structure of some of them have Hospital), sponsors the British Journal of Cancer been carried out by J. Monteath Robertson at the (now ending its 10th year), and organizes occa University of Glasgow, by J. Iball at the Uni sional informal scientific conferences. Through its versity of St. Andrews, and by R. Mason at Clinical Cancer Research Committee, the Cam University College, London. paign has also been able to make a notable con Apart from chemical agents, the subject of tribution to our knowledge of the incidence and carcinogenesis by ionizing radiations continues to natural history of cancer in its major forms. assume increasing importance in Britain as else Any attempt to survey adequately recent or where, and special note is drawn to the survey current work must of necessity fail, and also be by Court Brown and Doll, in part prepared for grossly incomplete, yet enough may be said to the recent Medical Research Council investigation give a rather general picture. In the field of of the hazards of nuclear and allied radiations, chemical carcinogenesis, a detailed study of the of leukemia in patients treated with x-rays for carcinogenic properties of mineral oils is being ankylosing spondylitis. The biological and chemi conducted by a Committee of the Medical Re cal basis of radiation effects is also being inten search Council. As to the mechanism of cancer- sively studied at such centers as the Medical producing substances, J. W. Orr at Birmingham Research Council Radiobiology Unit at Harwell,

Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1956 American Association for Cancer Research. HADDOWâ€”Cancer Research in the United Kingdom 823 where Loutit and Ford have recently conducted cell, much stimulus has come from the proposal their noteworthy experiments on the mechanism of Watson and Crick as to the structure of DNA, of protection by bone marrow; at the Institute and from the work of Wilkins and others at the Wheatstone Physics Laboratory, King's College, of Cancer Research by Mayneord and Lamerton ; at the Medical Research Council Radiotherapy London, upon which it was partly based. In Unit at Hammersmith Hospital; at the Depart particular, J. A. V. Butler and his school at the ment of Radiotherapeutics in Cambridge, under Institute of Cancer Research have studied the J. S. Mitchell; and at Mount Vernon Hospital, structure and function of DNA, the action upon where Gray continues his studies of tumor re it of the alkylating carcinogens, and certain ap sponses with variation of oxygen tension. Radia parent abnormalities in the nucleic acids from tion chemistry proper continues to advance many tumors. In the broader field of cancer bio through the work of F. S. Dainton (University of chemistry must be included the work of the Leeds), J. Weiss and G. Scholes (University of Courtauld Institute of the Middlesex Hospitalâ€”by Durham), W. M. Dale (Christie Hospital, Dickens, on the hexosemonophosphate oxidative Manchester), and C. B. Allsopp (Guy's). pathway of carbohydrate metabolism in normal A marked feature of British cancer research in and tumor tissues and on aromatization in vivo; the past few years has been the steady growth by Kellie, on the excretion of steroids in relation of statistical and field studies, a specially good to malignant disease; and by Doddsâ€”in keeping example being seen in the survey, by R. A. M. with the great tradition of the placeâ€”on the Case, on behalf of the Association of British Chemi natural estrogen of subterranean clover (5,7,4'- cal Manufacturers, of the incidence of papilloma trihydroxywoflavone). Other recent biochemical and carcinoma of the bladder in the dye-stuff contributions of interest are those of C. E. industry. The most spectacular application has, Dalgleish (Post-graduate Medical School of however, been in the work of Doll and Hill (Sta London), on the relation between 5-hydroxytryp- tistical Research Unit of the Medical Research tamine and tumors; of Boyland, on the role of Council) on the statistical association, in inquiries 0-glucuronidase and tryptophan metabolism in both retrospective and prospective, between lung relation to cancer of the bladder; and of D. H. cancer and the cigarette habit. The association Adams (London Hospital), on liver catalase. appears incontrovertible, and the simplest ex In the realm of tumor viruses, much improve planation would seem to be that it reflects a causal ment has taken place since the earlier days when relation. However, in spite of much excellent work the proponents and opponents of the so-called on the chemistry of cigarette smoke (for example, virus theory were arrayed in opposite schools, in by A. J. Lindsey at the Sir John Cass College, a kind of false antithesis. This situation certainly London), experimental verification still eludes us, produced extraordinary characters, each with his and in particular there is still no confirmation, gospel, but was perhaps not helpful toward any in the hands of such workers as Passey (Institute solution. The more recent work recognizes the of Cancer Research), Woodhouse (Birmingham), obvious need to integrate all available facts in and several others, of the positive results obtained the final picture, as in the demonstration by M. by Wynder in the United States, following appli A. Epstein (Bland-Sutton Institute) of presump cation of cigarette smoke condensÃ¢testo the skin tive intra-vacuolar virus particles in the Rous of mice; the cause of the discrepancy is still being sarcoma, and their quantitative correlation with sought. This and very many other circumstances biological activity; and the virus transfer of the suggest that the problem is by no means direct Rous sarcoma to turkeys by R. J. C. Harris or simpleâ€”especially, perhaps, the differing in (Institute of Cancer Research), employing pre cidences of lung cancer as between town and treatment of 1-day turkeys on the principle of country, a feature which has been studied by Percy acquired tolerance established by Medawar, Stocks in the Liverpool and North Wales area, Billingham, and Brent. This last principle, con with reference to atmospheric pollution. As in firming a prediction earlier made by Burnet and many other problems a survey of the field in Fenner, represents one of the main advances in general is the function of a special committee of modern immunology. The general upsurge has the Medical Research Council, although in this also been reflected in a revival of interest in tumor case much of the work is supported through immunology, in the work of Gorer at Guy's the Council by a subvention from the tobacco Hospital, in the theory of carcinogenesis by anti industry. gen loss put forward at Leeds by H. N. Greenâ€”in As to the more intimate chemistry of the cancer many ways so attractive but nevertheless de-

Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1956 American Association for Cancer Research. 824 Cancer Research pendent on a good deal of experimental verifica chemotherapy is on a smaller scale than that in tion still to be doneâ€”and in the observation by the United States, although it is likely to be much Darcy (Institute of Cancer Research) of a plasma expanded. component associated not only with malignant Mention should be made of certain investiga disease but also with active regeneration. tions which, if of less obvious direct relation to Apart from the experimental attack, the sphere the cancer problem, may be of no small importance of special pathology still continues active and on that account. Examples are seen in the studies clearly shows that no avenue of approach should of the energetics of cell division by Bullough be regarded as exclusive of any other. Particular (Birkbeck College, London), of the mitotic process examples are seen in the continuing study by generally by Swann (Dept. of Zoology, University Dukes (St. Mark's Hospital) of the relationships of Edinburgh), and of cell motility and cell surface to malignant disease of familial intestinal polyposis properties by R. J. Goldacre, E. J. Ambrose and of chronic ulcerative colitis, in Bodian's sur (Institute of Cancer Research), and M. Aber- vey of tumors in childhood (at the Hospital for crombie (University College, London). Sick Children), and in Thackray and Handley's Even if the above account is of necessity in investigation (at the Bland-Sutton Institute) of complete, enough has been said to show that the the importance of the internal mammary lymph approach is, in general, wide. Inevitably it pro chains, which are involved in about one-third of vokes comparison with that in the United States. all cases of mammary cancer at the time of mas Each has its virtues, and perhaps the ideal is to tectomy. be found in a blend of both. This summary would What are the benefits of all the cancer research be incomplete were it not to include some reference thus far carried out, in practical terms applied to to the characteristic American generosity be the average patient? Admittedly they are small, stowed upon many British laboratoriesâ€”including and it seems that a certain build-up is required my ownâ€”by such agencies as the U.S. Public before we can expect any revolution in treatment. Health Service, the Jane Coffin Childs Memorial Nonetheless, much present-day work is based on Fund for Medical Research, and the Anna Fuller the not unreasonable assumption that the disease Fund, and which, especially in the years im will ultimately be susceptible to chemical control, mediately after the War, proved of inestimable even if by chemotherapeutic methods vastly dif service. We hope, through the British National ferent from those we employ today. On the way, Committee on Cancer, to make some recompense useful applications have been found, if in a limited on the occasion of the Vllth International Cancer sense, in the examples of myleran and chloram- Congress to be held in London on July 6th-12th, bucil in the amelioration of chronic myelogenous 1958. leukemia and of the malignant lymphomas, re ALEXANDERHADDOW spectively. An interesting observation (made at the Hospital for Sick Children) concerns the action Chester Beatty Research Inst. of vitamin Bi2 in raising the frequency of regression Institute of Cancer Research in neuroblastomaâ€”still, however, to be fully con Royal Cancer Hospital firmed. In general, the study of experimental London, England

Cancer Res 1956;16:821-824.

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