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. INDIVIDUAL REPORTS 433 Dr. R. W. Rawson, Head of the Section of Clinical Investigation, finds that oophorectomy in cancer of the breast is beneficial for about 9 months in about 50 per cent. of pre-menopausal cases, and about one-half of these respond to adrenalectomy for a further 9 months. In post-menopausal women a beneficial effect is shown by oophorectomy in about 10 per cent. ; but by adrenalectomy in 50 per cent. of cases. Six out of fourteen hypophysectomies caused improvement for 2 to 4 months ; the arrest of growth is annulled by giving growth hormone. In, carcinoma of the prostate adrenalectomy causes transient improvement. Dr. Robert Mellors, Head of the Section of Cytochemistry, was examining the distribution of fluorescence in frozen sections of the skin of mice from a few hours to 7 days after application of carcinogenically active and inactive condensates of cigarette smoke prepared by Dr. E. R. Wynder. Controls are unpainted or receive solvent only. Dr. F. W. Stewart, Head of the Section of Pathology, and Dr. Fraser Foote, Associate, do not consider that duct stasis is a factor in the causation of mammary cancer, and claim to have converted the late Dr. James Ewing to this view. Possibly such factors vary in different countries at different times. They were interested in microphotos of Dr. I. Hieger's cholesterol sarcomas and considered these tumours to be obviously malignant. Dr. E. R. Wynder, in addition to his work on tobacco at the Sloan-Kettering Institute, directs a section of the Epidemiology of Cancer, in which about six women collect, from the literature and by correspondence, data about the geographical distribution of cancer. He is now visiting Copenhagen, Stockholm, Oslo and Reykjavik in pursuit of these studies. I had interesting talks also with Dr. Earl Balis, of the Section of Protein Chemistry, on the possibilities of purine synthesis in normal and malignant tissues, and with Dr. Maurice M. Rapport, Head of the Section of Immunology. YALE UNIVERSITY On 13th May, through the kindness of Professor Gardner, I had the opportunity to meet, at his house in the country, about a dozen persons associated with Yale, and with the Anna Fuller Fund, and was able to thank the representatives of the Fund for various grants received from them. Experimental Carcinogenesis Professor W. U. Gardner has in hand a considerable amount of investigation upon the induction of cervical and vaginal cancer, and of leukaemia, in mice. Local application of oestrogens to the cervix or vagina produces cancer more rapidly than does systemic administration. C57 mice are about 4 times as sensitive as

434 BRITISH EMPIRE CANCER CAMPAIGN A mice, and hybrids about 3 times, to the induction of vaginal cornification by oestrogens, and the vaginal mucous membrane of either strain retains its character in this respect after transplantation to the other. Gonadectomy increases the incidence of leukaemia which X radiation induces in mice, while after such irradiation in the intact animal oestrogens increase the leukaemogenic effect and androgens lessen it, the former acting early, and the latter late, in the post-radiation period. Professor Gardner is examining also the effect of hypo- and hyper-thyroid states (induced by thiouracil, and by feeding with thyroid) and of low calorie diets, upon tumour induction in mice. Chemotherapeutic research can of course be carried on by testing individual compounds without the screening of immense numbers of which the great majority are useless for the purpose in view. Dr. Arnold Welch (Department of Pharma- cology, Yale) whose staff consists of twenty graduates and twelve technicians, is opposed to the testing of compounds more or less at random and selects compounds which appear to be competitive analogues in the metabolism of various strains of bacteria. Such pairs of compounds are :-Uracil and 6-azauracil Thymine and Frazathymine The synthesis of 6-azauracil is the result of a very interesting series of reactions. The effect of this compound upon lymphoma of the mouse was so encouraging that Dr. Welch was just starting for Bethesda to arrange for trials upon human subjects. The metabolism of pyrimidines in the rat is being studied by means of labelling with 1tC. Other interesting observations by Dr. Welch are :- 1. That carcinoid tumours of the intestine in man form serotonin (5-hydroxy- tryptamine) which is excreted in the urine as 5-hydroxy indole carboxylic acid, which establishes the diagnosis of carcinoid tumour. 2. That orotic acid in some strains of mice lessens the production of tumours of the ' lung by urethane, while malic acid has the opposite effect. Dr. Harry S. N. Greene, Professor of Pathology at Yale, has for many years studied the transplantation (autologous, homologous and heterologous) of tissues (adult, and embryonic organs, benign and malignant tumours). Such investigations have been affected by the introduction of cortisone. A few years ago he trans- planted successfully thirteen human lung cancers obtained at operation to the eye or brain of guinea pigs (not less than eight animals in each case). All the turnours were epidermoid and all the patients died within a few months. The intracerebral graft displaces about one-half of a cerebral hemisphere in 40-60 days, when the animal dies. Similar transplantations of other epidermoid tumours (tongue, hypopharynx, larynx, breast, skin, lip, cervix) have not succeeded in more than one-half of the cases. Since "heterotransplantability does not characterise tumours from their inception but is an attribute attained late in the course of development"

INDIVIDUAL REPORTS 435 (Greene, 1953), this last consideration suggests that some of the carcinomas in situ of the lung described by Dr. Auerbach (see above) may have been present for a considerable time before diagnosis, and this may be the basis of the success of these grafts. Dr. Greene drew my attention to two cases of sarcoma in women, one fatal, arising at the site of injection of penicillin in sesame oil into the buttock. Sesame oil is one of the media often used in the testing of compounds in animals for carcinogenic action. HARVARD UNIVERSITY AND THE MASSACHUSETTS GENERAL HOSPITAL Cholesterol as Carcinogen I had two very valuable talks with Dr. L. F. Fieser (Professor of Chemistry at Harvard). About four years ago I drew his attention to the importance, which he recognised at once, of Dr. I. Hieger's discovery of the carcinogenic action of pure cholesterol. The questions, whether the most highly purified cholesterol is a single substance, and whether it is the mother-substance of a carcinogenic compound, in no way lessens the value of this discovery. Dr. Fieser has prepared various derivatives of cholesterol, and allied compounds, namely lathosterol (d7-cholestenol), cholesterol-a-oxide, 6fl-hydroxy-d'-cholestene-3-one, cholestenone (d'-cholestene-3-one), d'-cholestene-3:6-dione, and, most recently 6-p-hydro- peroxy-d4-cholestene-3-one. These compounds are being, or have been, tested for carcinogenic action by Dr. Fritz Bischoff, of the Santa Barbara Cottage Hospital, California, who uses the Marsh-Buffalo strain of mice. He describes the tumours produced as'fibro-sarcomas of the skin,' but in all his papers, from 1946 onwards he has never shown a single microphoto, although the three American journals devoted to cancer allow most lavish illustrations in such matters. Dr. Fieser regards the last of the six compounds named above as of especial importance, and Bischoff reports 'fibro-sarcomas of the skin' in 60 per cent. of mice painted with it. Dr. Fieser has sent this, and some other compounds, to Dr. Hieger for tests on mice. He is searching for derivatives of cholesterol in human and animal tissues and has begun experiments to show whether the production of such compounds can be influenced by diet. He finds that lanosterol makes up about 5 per cerit. of the crude cholesterol of the skin but only about 0-3 per cent. of that from other organs. The microphotos which Dr. E. K. Dawson of the University Laboratory, Edinburgh, has published showing the accumulation of fatty material and cholesterol in some precancerous conditions of the breast suggest the possibility of scooping out such portions and placing them in tubes which could be sent to Dr. Fieser for chemical and spectroscopic examination. He can determine cholesterol, cholestenol, lathosterol and 7-dehydrocholesterol on a 10 mg. sample, but if 7-dehydrocholesterol be left out a mg. or two is enough. I hope that it may be possible to arrange for such samples to be sent to Dr. _Fieser, and this method might be applicable to the lung and other organs.