TESTING CANCER CURES

TESTING CANCER CURES

664 theatre and all its works. Despite firm assurance that fortunate or they might avoid treated areas. For several tropical diseases it- is important...

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664 theatre and all its works. Despite firm assurance that fortunate or they might avoid treated areas. For several tropical diseases it- is important, to prevent -insect the operationwill be painless, it is’an ordeal for them to bites rather than to prevent chronic infestation. Rebe awake : the grating of -bones frightens them and pellents serve a useful purpose here, and some remarkably they cannot endure the thought of the knife. Since we effective new ones have been found. Dimethyl phthalate cannot separate the man from his disease, Macintosh is one of the most widely used of these." But some pests and Mushin insist that his wishes must be respected ; if are specific in their dislikes so that other substances or he asks for unconsciousness he must have it, unless there mixtures may be used for particular purposes. At first is some definite contr-indication. the obvious method of using repellents was by smearing TESTING CANCER CURES them on the skin. But it has been found that with THE testing of supposed cancer cures looks at first impregnated garments or wide-meshed veils the effect lasts much longer.9 Apart from the Russian experiments sight simpler than it is. No two human tumours behave quoted, a great deal of investigation is going on in this exactly alike in the symptoms they produce or their -rate country and America which will probably be kept secret of growth or spread and killing capacity ; thus in tests on humans no strictly comparable control observations until the end of the Japanese war. Butventually these can be made. Moreover, it is useless to assess results innovations will become generally available for public use, until at least 5 years have gone by. Bold experiments and then we shall have new measures of protection with substances are of course ruled out, poisonous mites. harvest fleas and against mosquitoes, midges, though such experiments made on animals might provide NERVE BLOCK IN THE ARM valuable information. Trial of a remedy on humans is BRACHIAL plexus analgesia is likely to. become popular, only worth while after it has been tested first against for modern technique makes it certain, simple and safe. malignant cells in tissue-culture, with normal cell Time was when the method was an ordeal for patient controls, next against transplanted tumours. and finally and anaesthetist, and there was much wriggling by the against spontaneous tumours in animals. This does parties at opposite ends of the needle. Blame cannot not of course apply when some drug whose pharmacology is already known is to be applied to the relief of cancer be laid at one door, however, for only in the very ill would the surgeon insist on a local anaesthetic ; and symptoms. The remarkable effect of stilboestrol in then, with hand untried and only an airy intuition as to r4lieving the symptoms of prostatic cancer could only the exact location of the brachial plexus, the anesthetist have been demonstrated in man. Further experiments often failed-and little wonder. But there has been a in animals may however yet be necessary to find out change of front : the method is no longer the potion of whether stilboestrol or some allied substance, possibly more poisonous, can produce an actual cure. the very ill; it finds its chief application in the very fit, the robust with strong muscle. In a little volume 10 Every cancer research institute which works systemMacintosh and Mushin show that there is no particular atically comes across substances -capable of killing art about injection of the brachial plexus, and that the malignant cells in culture. Reports on these substances operator needs no mystical nerve-divining qualities seldom appear in print because they are apt to give rise to false hopes One substance of this kind has lately for success. All turns on knowledge of the anatomy, and received wide publicity, especially in America. It is the key to success, as Macintosh and Mushin point out, found in some impurity associated with the yellow is the first rib. The operator must be able to picture that rib accurately in his mind’s eye, and to trace it pigment of penicillin, and, though penicillin itself will not; destroy tumour cells, Cornman1 and M. R. Lewis have with the point of his needle. In simple lucid language they describe how this can be done. Teaching is like demonstrated that this impurity has the property of propaganda-a measure of- over-emphasis is essential. killing them while leaving normal cells alive. Earlier Macintosh and Mushin show themselves good teachers : trials in this country on crude penicillin failed to -reveal the anatomy and the method are made palpably clear, any lethal activity on tumour cells, but this negative result does not throw doubt on the American finding, even for the novice, by an abundance of anatomical " drawings in which every step is Mickey-Moused." The for samples of crude penicillin vary widely. The natureB of the tumour-cell-destroying substance in the American method they present is that described by Patrick in 1940, to which they have added their own improvements. product has yet to be determined, as well as the margin It depends on the saturation by local anaesthetic of the between the lethal dose for tumour cells and the survival area of the first rib where the brachial plexus crosses it. dose for normal ones. Usually for such substances the The first and fundamental step in the operation is margin of discrimination is narrow. Thus a compound accurate localisation of the subclavian artery as it given to a mouse in suitable dosage may cause a tumour crosses the rib. -The older methods relied on transfixing to shrink until it is barely palpable, and sections show the brachial plexus ; as soon as par2esthesiae were a shrunken mass of dead cells and connective tissue ; obtained the injection was made. But such paraesbut if no further treatment is given the apparently dead thesise, as they point out, are felt by only 3 out of 4 tumour comes to life and grows again-yet even one patients-; and the old methods were so disappointing more ctose of the compound under trial will kill the that brachial injection came to be used only occasionally. The margin of discrimination may sometimes’ mouse. be lost because the agent is unevenly distributed through Macintosh and Mushin find that by using a 1% solution the body of the animal. And in the preliminary tests of procaine it is possible to make the limb insensible yet to leave it capable of full motor power ; this has with cell-cultures the normal controls consist of a single great advantages for the operating surgeon-for example, type of cell that happens to live readily in culture; in tendon repair. Surgeons have been reluctant to whereas in the body a vast variety of cells which have employ this method in shocked cases, feeling it- might never been tested are exposed to the agent. Other well add to the shock ; but with appropriately reduced pitfalls inherent in the test have already been discussed in these columns.2 dosage, it seemingly adds nothing to the risk. It is unfortunate that in every character save one However simple the method and however adept the operator, many patients have horror of the operating- malignant and normal cells resemble one another closely. The exceptional property of malignant cells 8. Phillip, C. B., Paul, J. R., Sabin, A. B. War Med. 1944, 6, 27. 9. Monchadski, A. S., Blagoveschenski, D. I., Bregotova, N. G., is autonomous growth. Whether the aim of a supposed Ukhova, A. N. Med. Parasitol. 1943, 12, 56. curative agent is tG kill the malignant cell by selective 10. Local Anæsthesia : Brachial Plexus. R. H. Macintosh, MD, action or to deprive it of some necessary FRCSE, Nuffield professor of anæsthetics, University of Oxford ; poisonous W. W. Mushin, MB, LOND., first assistant in the Nuffield 1. Cornman, I. Science, 1944, 99, 247. department of anæsthetics. (Blackwell Scientific Publications. Pp. 56. 10s. 6d.) 2. Lancet leading article, 1944, i 569. Kennaway, E. L. Ibid, p. 647.

665 Recent susceptibility of the pancreatic- islets of the monkey to the action of alloxan may well encourage those who hope to find in this drug a means of destroying malignant although- as many as 12,564 egg-whites were given to islet-cell tumours. Two main hypotheses have been advanced to explain one patient in 315 days. Very likely had any result the transitory hvpoglycaemia seen in alloxan-treated been evident host and tumour would have shown equal animals before they develop hyperglycaemia due to islet effects of deprivation-just as in crymotherapy both necrosis. The first, propounded by Shaw Dunn et al., suffer from lack of fluid. This lavish but ineffectual use of egg-white demonstrates again that the human suggested that alloxan stimulates the islet cells to oversubject is unsuitable for first tests. Of the three test work, and that in pouring out the insulin that lowers the methods, the effect on standard tumours in inbred blood-sugar the cells are exhausted and die. According to the second hypothesis, advanced by Hughes, Ware animals is for the present far the most reliable. and Young,6 the primary effect of alloxan on the islet UNIVERSITY DEPARTMENTS OF INDUSTRIAL cells is toxic, and the hypoglycsemia results from the HEALTH washing out of pre-formed stores of insulin from dead or GREAT BRITAIN has at present no university departdying islet cells. In support of this idea Hughes et al. ment devoted to educational work in industrialhealth, showed that the amount of extractable insulin known to and scarcely any facilities for postgraduate training in be present in the pancreas of the rabbit was sufficient, industrial medicine. In January, 1943, a select comwhen administered to normal rabbits in the form of mitteeof the House of Commons, reporting on the health protamine-zinc-insulin, to bring about a phase of and welfare of women workers, rightly remarked that hypoglycaemia similar to that seen after a necrosis" doctors who are new to industrial work have to learn inducing dose of alloxan. Evidence further suppqrting slowly and painfully by experience many lessons that this hypothesis has lately come from the laboratory of should and could be taught in courses of preliminary Prof. C. H. Best in Toronto, where it has been shown7 training if such were available." It is good news, that though, in both rats and dogs, injection of alloxan therefore, that the Nuffield Foundation has offered the reduces the insulin content of the pancreas, the pancreatic universities of Durham, Glasgow and Manchester grants insulin does not diminish until some time after most of totalling :E 150,000 to assist them to carry out schemes the islet cells have died. Evidence that the hypothey have submitted for the development, as soon as glycaemic action of alloxan is the result of its action on suitable staffs can be appointed, of teaching and research the pancreas rather than on the liver or other tissues was in industrial health. These grants will be spread over obtained by giving alloxan to dogs previously rendered ten years. Manchester, where it is proposed to create a diabetic by pancreatectomy or by administration of chair of industrial health, will receive 70,000. Durham alloxan, the diabetes being controlled by administration has been offered 40,000 for the establishment of a of PZI. In diabetic dogs alloxan did not exert a department under a university reader, and a similar transitory hypoglycsemic action, though this was amount is being allocated to Glasgow for a subdepartpronounced in normal dogs receiving alloxan. The ment of industrial health within the existing department investigators conclude that the cause of the hypoof social medicine. glycaemia is that alloxan kills islet cells and thus allows their contained insulin to be leached into the blood-stream. ALLOXAN AND THE PANCREATIC ISLETS It now remains to be determined why alloxan acts RESEARCH on the action of alloxan, stimulated by the particularly on islet cells, and how it causes their rapid late Professor Shaw Dunn and his colleagues,4continues necrosis. to give interesting and important results. His original HINTS AND TIPS FOR THE TUBERCULOUS observation that intravenous injection of alloxan can cause rapid necrosis of the’ pancreatic islets has been THE school of wishful thinking which maintained amply confirmed, and is known to be true for rats and that tuberculous patients fared best when in ignorance dogs as well as for rabbits. Brunschwig et al.,5 who about their disease is dying fast. A patient when first injected alloxan intravenously into four human patients diagnosed as suffering from tuberculosis usually suffers with carcinomatosis, report transitory benefit in one of more intensely still from tuberculophobia and feels them who was suffering from hyperinsulinism resulting impelled to ask questions and to seek reassurance. To from islet-cell carcinoma ; after the administration some 0:Þ his questions his family doctor may not be any of alloxan, hypoglycsemic symptoms were abolished for too sure of the answers. The chest specialist to whom 10-20 days, whereas before treatment there had been he may next be referred very likely has a way of putting 2-5 attacks each day. The other three patients received things different from the GP’s. On arrival at the doses larger (per kg. body-weight) than are required to sanatorium the patient finds that the physicians there produce islet necrosis in dogs and rabbits, but the too seem to speak a different language, and moreover blood-sugar level was affected in only one case, and then to exhibit a different approach to the whole subject. but slightly. From this it was concluded that man is On the other hand there are patients who display no more resistant to the action of alloxan than is the dog or lively curiosity about their complaint and who submit the rabbit, and the more interest therefore attaches to with unquestioning docility to whatever is prescribed Banerjee’s description, elsewhere in this issue, of hyper- for them. Some of these are doubtless too engrossed glycsemia and islet changes in monkeys treated with a in other problems. A few may be too dumb ; but v single moderate dose of alloxan (300 mg. per kg.) by many of them are deterredfrom "asking too many " intravenous injection. Banerjee suggests that Brunquestions " lest they be labelled as." introspective or schwig’s observation that alloxan did not affect the islet " neurotic." And yet, to quote Dr. G. S. Erwin’s tissue in his case of islet-cell carcinoma may be ascribed preface to his Guide for the Tuberculous Patient (Heineto the use of too small a dose. A demonstration of the mann, pp. 112, 3s. 6
foodstuff, both tumour and host usually suffer.

tests on human tumours with avidin (egg-white)3 have failed to starve either the tumour or the host of biotin,

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i, 484 ; Dunn, S., Kirkpatrick, J., McLetchie, Telfer, S. V. J. Path. Bact. 1943, 55, 245 ; Dunn, J. S., and McLetchie, N. G. B. Lancet, 1943, ii, 384 ; Dunn, J. S., Duffy, E., Gilmour, M. K.; Kirkpatrick, J. and McLetchie, N. G. B. J. Physiol. 1944, 103, 233. 5. Brunschwig, A., Allen, J. G., Goldner, M. G. and Gomori, G. J. Amer, med. Ass. 1943, 122, 966 ; Brunschwig, A., Alien, J. G., Owens, F. M. and Thornton, T. F. Ibid. 1944, 124, 212 ;

Brunschwig, A. and Allen, J. G. Cancer Research, 1944, 4, 45.

treatment can be influenced evil, by the patient himself."

for the outcome of the

materially, for good

or

Dr. Erwin’s little volume is accurate and well balanced : it cannot fail to dispel the terrors of the unknown, and 6. Hughes, H., Ware, L. L. and Young, F. G. Lancet, 1944, i, 148. 7. Ridout, J. H., Ham, A. W., Wrenshall, G. A. Science, 1944, 100, 57.

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